parental permission/consent form for research ic pp 10-01-15.pdfstay, laboratory studies and ecg...

Main ICF – HOPE Duchenne Version Date: 10.01.2015 of 28

PARENTAL PERMISSION/CONSENT FORM FOR RESEARCH

TITLE: A Randomized, Open-label Study of the Safety and Efficacy of Multi-Vessel Intracoronary Delivery of Allogeneic Cardiosphere-Derived Cells in Patients with Cardiomyopathy Secondary to Duchenne Muscular Dystrophy [HOPE-Duchenne]

SPONSOR: CAPRICOR, INC. PARTICIPATING RESEARCHERS: Ronald Victor, MD Principal Investigator 310-423-3300 Ruchira Garg, MD Co-Investigator 310-423-3300 Raj Makkar, MD Co-Investigator 310-423-3300 Eduardo Marban, MD, PhD Co-Investigator 310-423-3300 Florian Rader, MD Co-Investigator 310-423-3300 STUDY CONTACT PHONE NUMBER AT CSMC: 310-248-8080 AFTER HOURS CONTACT (24 HOURS): 310-248-8080 This research Study is sponsored by Capricor, Inc. Capricor, Inc. only reimburses Cedars-Sinai Medical Center for the costs associated with running the Study; Capricor, Inc. is not providing additional compensation to Cedars Sinai Medical Center or the Principal Investigator for their participation in the Study. 1. WHAT IS THE PURPOSE OF THIS RESEARCH STUDY?

This Study involves research about an investigational product called CAP-1002. An “investigational product” means CAP-1002 is being tested and has not yet been approved by the U.S. Food and Drug Administration (FDA) for use by the general public. CAP-1002 is a biologic product consisting largely of adult heart stem cells grown from donated tissue from adult heart muscle. The purpose of this Study is to evaluate the safety and effectiveness of CAP-1002 in cardiomyopathy (heart muscle disease) related to Duchenne muscular dystrophy (DMD). Cardiac dysfunction (impaired or abnormal functioning) is a frequent symptom of DMD which leads to heart failure and abnormal heart rhythms. The Study will collect information on the safety of CAP-1002 in DMD patients; and examine whether CAP-1002 can decrease the amount of heart muscle damage, improve heart function, or possibly delay the progression of damage to the heart. In this Study, we will be investigating whether CAP-1002 is safe and effective in repairing heart tissue or in delaying continuing heart damage in subjects with DMD. Additionally, we will be watching for any side effect, good or bad, that CAP-1002 has on study participants. You are being asked to participate in this Study because you have been diagnosed with Duchenne muscular dystrophy and may have cardiac dysfunction. Additionally, you have either

Study ID

: HS

-15-00547 Valid From

: 10/1/2015 To: 9/30/2016


been recommended by your physician to participate as a subject in this Study or deemed to be a potential subject for this Study based on a review of your medical history. Before agreeing to participate in this Study, you should read and understand the following explanation of the purpose, risks, and procedures of the Study. This Informed Consent Form provides information about the research Study and describes the purpose, procedures, benefits, risks, and precautions of the Study. Please ask the Study doctor or Study staff to explain any information in this form that you do not understand. When all of your questions have been answered and you feel that you understand the Study, you will be asked if you want to participate in the Study and to sign this Informed Consent Form. After signing this form, you will be given a copy of the signed form to keep for your personal records. Your participation in this Study is voluntary. If you decide not to participate in this Study, you will not lose any benefits to which you are otherwise entitled and it will not affect your ability to obtain treatment outside of this Study. If you agree to participate in this Study, you may withdraw from this Study at any time without penalty or loss of benefits to which you are otherwise entitled. The Study will enroll and screen up to 48 people in total at approximately 5 different clinical research sites in the U.S. 2. WHAT WILL HAPPEN DURING THE STUDY? This section provides a general overview of what will happen during your participation in this Study. Information included below should be considered along with the flowchart of procedures attached as Appendix A. No Study procedures listed in Appendix A, including those to make sure you are eligible to participate, will be performed on you in connection with this Study until you agree in writing to participate and sign this Informed Consent form. You must continue to meet eligibility criteria throughout the screening process and through randomization to either CAP-1002 or usual care in order to continue to participate in the Study. The flowchart shows a timeline for research-related procedures that are involved in your participation in this Study. Research-related procedures are those performed solely for the research. They would not be performed if you did not take part in the Study. A table describing common medical procedures done solely for the purposes of monitoring and assessing your condition during this Study is attached as Appendix B at the end of this consent form. Overview of Study

This Study will be conducted as an open-label, randomized study. “Randomized” means that a computer will randomly assign you to a Study group by chance, like flipping a coin. This means that if you meet all of the required criteria for participation in the Study, you will be randomized to one of two groups, CAP-1002 or usual care. If you are randomly assigned to receive CAP-1002, your doctor will be using a catheter to infuse CAP-1002 in the arteries of your heart.

Study ID

: HS


: 10/1/2015 To: 9/30/2016


• Group 1 will be at least 18 years of age, and receive either CAP-1002 or usual care. • Group 2 will be enrolled after safety information from Group 1 has been reviewed,

and will receive either CAP-1002 or usual care. Subjects in Group 2 will be at least 12 years of age.

“Usual care” is the normal care a patient with DMD would receive for the condition. In the Study, you will have a 1 in 2 chance (50%) of being randomized to receive usual care alone or usual care plus CAP-1002. Research participants in this Study will get either their usual care plus an infusion of CAP-1002 or usual care alone. Open-label means that you, the Study doctor, and Study staff will know whether you have been randomized to receive CAP-1002 or usual care. Once you are assigned to a Study group, you cannot switch to another Study group. If you are assigned to the CAP-1002 Study group, CAP-1002 will be given by infusion down the coronary arteries into your heart’s tissue using a catheter. A single dose of CAP-1002 consists of about 25 million cells suspended in about 1 tablespoon of an infusion solution. CAP-1002 will be administered by infusing 3 doses of the Study product using a TERUMO Finecross™ MG catheter to move the Study product to coronary arteries. This catheter is not approved for infusing biological agents such as CAP-1002. It is approved by the FDA to infuse contrast (imaging “dye”) into the arteries of the heart and to support a special wire into the arteries to treat blockages. This catheter was chosen because it is similar to other catheters previously used and has the capability to deliver CAP-1002 as intended. It has not been approved by the FDA for this type of infusion. You will be brought to the cardiac catheterization laboratory to undergo a cardiac catheterization where a catheter is inserted through the skin and into the artery. This procedure is similar to when people have blocked coronary arteries. However, rather than opening a blocked artery, CAP-1002 will be infused into coronary arteries that supply blood to the three cardiac territories. The plan is to infuse 1 dose of up to 25 million cells into each of 3 main arteries in your heart. However, your Study doctor may decide that it would be better for you to receive fewer cells (12.5 million) in 1 or 2 arteries. So, based on that decision, if you are randomized to CAP-1002, you will receive a total of 50-75 million cells during the infusion.

The infusion of CAP-1002 takes about 1 hour with 3-5 additional hours for recovery afterwards. You will remain in the hospital for 20 to 24 hours after your infusion procedure. During your stay, laboratory studies and ECG monitoring will be performed to rule out cardiac injury or a heart attack. When you are discharged from the hospital, you will go home with an ambulatory heart monitor which will record your heart rate and rhythm for 24 hours.

Another way to find out what will happen to you during the Study is to read the chart below. Start reading at the left side and read across to the right, following the lines and arrows.

Study ID

: HS


: 10/1/2015 To: 9/30/2016


If you are randomized to usual care, you will be followed as you receive the care generally followed for individuals with your condition. Standard (routine) care and research-related procedures for subjects randomized to the usual care will involve all of the same tests as those subjects randomized to CAP-1002 except for the infusion procedure. All randomized subjects will be followed out to one year post-randomization (usual care arm) or post-infusion (active treatment arm). During the first year, on site follow up visits will be performed, at 2 weeks, 6 weeks, 2 months, 6 months, and 12 months after the study randomization visit. Annual follow-up phone calls will be conducted for an additional four years and will be timed to be conducted at the same time as your normal, annual clinical follow-up which may include annual cardiac MRI where clinically indicated. This Study will also investigate if CAP-1002 has an effect on the amount of certain biomarkers in your blood. A biomarker is a biological molecule that is present or absent in blood, other body fluids, or tissues that may be a sign of a condition or disease. The biomarkers that will be measured include Osteopontin and Galectin-3 which are related to increased work being done by your heart. ST2 and Interleukin-10 will also be measured; these biomarkers are related to the immune response of the body, as well as cell migration and attachment. Optional Sub-Study Details of an optional Exploratory Biomarkers sub-study are described in a separate consent form. The decision to allow your blood to be analyzed for exploratory biomarkers is voluntary and optional. You may participate in this research Study regardless of whether you consent to participate in the Exploratory Biomarkers sub-study. How long will you be in the Study We think you will be in this Study for about 13 months and includes about 7 visits to the Study doctor at the Study clinic and one overnight stay at the hospital (if randomized to receive CAP-1002). You will visit for screening procedures, infusion (if randomized to receive CAP-1002; this is an overnight stay in the hospital), Weeks 2 and 6, Months 3, 6 and 12 for about 13 months. We would like to keep track of your medical condition for approximately one year after you are randomized to either CAP-1002 or usual care. We would like to review your medical records to see how you are doing. Keeping in touch with you and checking on your condition every so often helps us look at long-term effects.

Randomization (The computer will

randomly assign you to a Study treatment)

Usual Care (Control Arm)

You agree to take part in the study &

Determine if eligible

CAP-1002

(Experimental Arm) Study ID

: HS


: 10/1/2015 To: 9/30/2016


3. WHAT ARE THE POSSIBLE RISKS? This section describes the possible risks and/or discomforts we anticipate you could experience that are related to the Study procedures. There also may be other side effects or risks that we cannot predict. Many side effects may go away shortly after the Study drug or procedure is stopped. However, in some cases they can be serious, long-lasting, permanent, and/or fatal. Risks of common medical procedures performed solely for research purposes are described in a table attached to the end of this consent form as Appendix B. The side effects and risks of standard of care procedures are not described in this consent form. Risks of the Experimental Stem Cells The most common side effects of administration of CAP-1002 include: Reduced Blood Pressure: A decrease in your blood pressure can occur during the cell infusion. This is related to the nitroglycerin in CAP-1002. Reduced blood pressure usually does not last long, only a few minutes. However, you may feel lightheaded or nauseous. Allergic Reactions: Though it has not been seen in animal or similar human studies, it is theoretically possible that an allergic reaction to CAP-1002 can occur. An allergic reaction could result in hives, rash, difficulty breathing, low blood pressure, or severe blood circulation and breathing problems. These reactions are usually reversible but in rare cases could lead to permanent disability or death. You will be under physician supervision during administration of CAP-1002. Bovine (cow) products are used in the CAP-1002 manufacturing process and then washed out. CAP–1002 contains dimethyl sulfoxide. If you have a known allergy to dimethyl sulfoxide or bovine products, you may not participate in this Study. There were no other side effects noted in animal studies using CAP-1002. However, you should know that a number of theoretical safety issues exist even though they have not been reported in the animal studies. These include:

1. potential contamination and infection; 2. immune reaction including rash and joint aches; 3. ectopic tissue formation or tumor (development of new tissue in an area of the body that

it would normally not be found, or development of a cancer); 4. development of antibodies to the cells: in patients with severe heart failure who may

require a heart transplant later, this increase in antibodies may make it more difficult to find a donor heart that matches well. Patients may wait longer on the transplant list than usual;

5. exposure to Epstein-Barr Virus (EBV) and Cytomegalovirus (CMV): EBV and CMV are very common in the general population, therefore it is possible that the donor of the heart tissue that was used to grow the cells had been exposed; and

6. myocarditis: this is inflammation (swelling) of the heart tissue in response to the Study product.

Study ID

: HS


: 10/1/2015 To: 9/30/2016


To minimize your risks, your blood will be tested to see if you have antibodies to the donor cells. CAP-1002 will also be tested for genetic abnormalities, which could make cells prone to tumor formation. CAP-1002 will be tested for infection, CMV and EBV prior to being shipped to Study sites. Only Study product that is free of infection, genetic abnormalities, EBV and CMV will be used in this Study. As with any new agent, there may be side effects and discomforts that are not yet known. In addition, Study subjects also may experience illness or death related to their underlying condition. Risks of CAP-1002 Infusion (if randomized to CAP-1002) Chest Pain or Pressure: During the infusion, it is not uncommon to feel some chest pressure or discomfort. The discomfort is usually temporary, lasting only for a couple of minutes. Your electrocardiogram and blood pressure will be continuously monitored during the infusion. The remaining infusion(s) will be stopped if you experience severe chest discomfort that lasts longer than three minutes after completion of the cell infusion into the first or second artery. A selective angiography (x-ray) is performed at the end of the infusion to determine if each artery has good blood flow. Drug Side Effects: There may be side effects related to drugs that will be used during the infusion or testing procedures. In particular, the following drugs will be used with the CAP-1002 infusion: • Heparin: Blood thinner used before the cell infusion; side effects include reddening of the

skin, hematoma (localized collection of blood), injection site sore, heparin-induced thrombocytopenia (low platelet count), mild pain, local irritation.

• Nitroglycerin: Used to treat or prevent chest pain. It works by relaxing the arteries which

increases the blood and oxygen to the heart. We use nitroglycerin in CAP-1002 to open up the heart arteries so CAP-1002 can get into your heart tissue more easily. Side effects include low blood pressure, headache, dizziness, lightheadedness and/or fainting.

VERSED: An anti-anxiety drug that can be used before the cell infusion at the discretion of

your study doctor. Side effects include nausea, vomiting, sleepiness, headache, drowsiness, cough, hiccups.

FENTANYL: A Pain reliever that can be used before or during the selective angiography and cell infusion at the discretion of your study doctor. Side effects include: constipation, nausea, sweating, intense itching, vomiting, dizziness, urinary retention, confusion, sleepiness, weakness, dry mouth.

LIDOCAINE: An analgesic that is used prior to the selective angiography and cell infusion. Side effects include swelling, hypotension (abnormally low blood pressure), reddening at injection site, skin irritation, constipation, nausea, vomiting, petechia (small red/purple spots on the skin that indicate a low platelet count), confusion, dizziness, headache, drowsiness, tremor, numbness/tingling, irritation symptom.

Study ID

: HS


: 10/1/2015 To: 9/30/2016


ATIVAN: An anti-anxiety drug that can be used before the MRI or cell infusion at the discretion of your study doctor. Side effects include drowsiness, dizziness, sleepiness, clumsiness or unsteadiness, weakness, and loss of memory, depression.

DILAUDID: An anti-anxiety drug that can be used before cell infusion at the discretion of your study doctor. Side effects include loss of appetite, nausea, vomiting, dizziness, drowsiness, weakness.

In addition, your physician may prescribe other common drugs for you which may have additional side effects. More serious but less common side effects of CAP-1002 include: Heart Rate and Rhythm Changes: Some subjects may experience a fast or irregular heart rate during the infusion procedure. This can cause shortness of breath, nausea, vomiting and lightheadedness. This sensation is usually temporary and resolves quickly once the procedure is completed. If the fast heart rate or irregular rhythm persists, the Study doctor may need to use medications to bring the heart rate or rhythm back to normal. Though it has not been seen in other similar studies, possible abnormal heart rhythm and sudden death caused by abnormal rhythm could occur. Your heart rate and rhythm will be continuously monitored during the infusion procedure and while you are in the hospital for approximately 24 hours after the infusion. Additionally, you will be monitored for abnormal rhythms using the 24-hour monitor after discharge and during the follow-up assessments. Cardiac Catheterization Risks (Selective Cardiac Catheter/Angiography using Fluoroscopy): The risks for cardiac catheterization include pain, infection or bleeding (at the site of insertion), ischemia (an insufficient supply of blood to the heart), irregular heartbeat, stroke, and heart attack. There is a small amount of risk due to radiation exposure (See Radiation Risk section below). Infusion Risks: CAP-1002 will be infused down your coronary arteries through an infusion catheter. There is a risk of cardiac ischemia, where the blood flow to the heart muscle can be obstructed decreasing the oxygen to the heart muscle, leading to heart attack. The wall of each artery can be injured or torn during placement of the infusion catheter necessitating stent placement. When high doses of cells are infused, there is a risk of clumping of the cells, which can decrease blood flow and result in injury to the heart muscle or a heart attack. We will use a dose of cells which has not been associated with injury in other human studies and we will be monitoring blood tests and your electrocardiogram frequently to determine whether any injury has occurred. Prior to the infusion, it will be necessary to perform a selective angiography (x-ray) to verify that the arteries of the heart are open. The radiation time used during the catheterization will be approximately two minutes. To minimize the risks associated with CAP-1002, your Study doctor will monitor your health status closely after your infusion procedure and test your kidneys, liver, lung and blood counts during the follow-up visits.

Study ID

: HS


: 10/1/2015 To: 9/30/2016


Unknown Risks There may be uncommon or previously unknown risks that might occur. You should report any problems to the Study staff. You have the right to ask any questions about the potential and/or known hazards of this Study at any time. You will be asked to tell the Study doctor about any possible side effects that you might experience at any time during the Study. There may be other side effects that we presently cannot predict. Many side effects go away shortly after the procedure is stopped, but in some cases they can be serious, long-lasting, and/or permanent. Reproductive and Lactation Risks Taking part in this research Study can affect an unborn baby. Therefore, you should not father a baby while in this Study. If your partner is capable of becoming pregnant you will need to use birth control. Check with the researcher about approved birth control methods to use while participating in this Study. Unknown Risks to the Developing Embryo or Fetus (an unborn baby) If your partner is pregnant, or becomes pregnant during participation in this research, the Study drug might involve risks to an embryo or fetus, which are currently unknown. It is important that you contact the researcher immediately if you believe your partner might be pregnant. Collection of Pregnancy Outcomes If your female partner becomes pregnant during the Study, we will ask your female partner for consent and authorization to collect information on the outcome of her pregnancy and the status of your child, including spontaneous or voluntary termination, details of the birth, and the presence or absence of any birth defects, abnormalities, or complications. Your partner is free to decline to consent to provide this information. This information will be collected from your female partner’s medical records with her permission. Follow-up Visit for Discontinuing Participants While you are free to discontinue your participation at any time, we encourage you to complete a Study Completion Visit (Month 12). During this visit, we will conduct tests to collect safety data, and discuss any information that may be important to share with your treating physician. Radiation Risk This study involves radiation exposure to Selective Cardiac Catheter/ Angiography using fluoroscopy, the radiation exposure is approximately 6 Rem. The amount of radiation exposure from Fluoroscopy and CINE used is expected to be less than other clinically performed procedures. The radiation dose in the research portion of the study is a maximum of 56Rem. This use involves acceptable risk and is necessary to obtain the research information desired. Incidental Findings It is possible that the research procedures could uncover information related to your health that you did not know about before and that is unrelated to the Study. Some of these findings may be too preliminary to share. Cedars-Sinai will carefully consider the research findings and determine if they should be shared with you. Research findings would only be shared with you if such sharing is approved by the Cedars-Sinai IRB and is permitted by applicable law. In some

Study ID

: HS


: 10/1/2015 To: 9/30/2016


cases, additional clinical testing may be required. The cost of any additional testing and any related treatment will be your responsibility. 4. ARE THERE BENEFITS IN TAKING PART IN THE STUDY? This is the first study in humans in which CAP-1002 is being tested for cardiomyopathy related to DMD. This Study is designed primarily to evaluate the safety and effectiveness of treatment with CAP-1002. If you agree to take part in this research Study, there may or may not be direct medical benefit to you. The possible benefits of taking part in the research Study include some improvement in cardiac function and decrease in size of cardiac damage, as demonstrated by previous research on similar cell treatments in animals and humans. However, no benefit is guaranteed. It is possible that your condition may remain unchanged or even get worse. Information learned from this research Study may benefit other individuals with cardiomyopathy secondary to Duchenne Muscular Dystrophy in the future by helping us to learn the potential benefits and risks of cell treatment. 5. WHY WOULD MY PARTICIPATION BE STOPPED? Your Study doctor, the Study Sponsor, its affiliates, or the FDA may decide to remove you from this Study for any reason, even if you would like to continue. Some examples of why you may be removed from the Study, with or without your consent, include the following:

the Study doctor determines that it is in your best medical interest; funding for the Study is reduced, stopped or withdrawn; you do not consent to continue in the Study after being told of changes in the research

that may affect you; you are unable to comply with the protocol; you have an adverse reaction to CAP-1002; you need a treatment not allowed in this Study; you do not keep appointments; if you are randomized to receive CAP-1002, but are unable to receive the infusion; the Study is canceled by CSMC, the FDA or Sponsor.

You may also decide to withdraw from the Study at any time. If you leave the Study, the researchers may continue to analyze and use the data previously collected from you before you withdrew from the Study. While you are free to discontinue your participation at any time, we encourage you to complete an Early Termination Visit if you do decide to stop participating in the Study. During this visit, we will conduct tests that would otherwise have been performed at your 12-month visit, and discuss any information that may be important to share with your treating physician.

Study ID

: HS


: 10/1/2015 To: 9/30/2016


6. YOUR RESPONSIBILITIES

You have the responsibility:

1. To provide, to the best of your knowledge, complete information about your current medical condition and past medical history, including current illness, prior hospitalizations, current medications, allergies, and all other health-related matters;

2. To discuss the Study treatment plan with the Study research staff before indicating your agreement to take part in the Study by signing this Informed Consent;

3. To inform the Study doctor or Study staff about your wishes regarding treatment plans. You may provide for a duly authorized family member or spokesperson to make medical decisions on your behalf in the event that you become unable to communicate;

4. To comply with your Study treatment plan, to cooperate with hospital staff, to ask questions if directions or procedures are not clear, and to participate in your health-care decisions. You may withdraw from the Study for any reason, but it is desirable to discuss your concerns with the attending physician before taking that action;

5. To report on time for scheduled procedures and to keep all clinic appointments. If unable to do so, you have the responsibility of notifying the Study staff and canceling and rescheduling the appointment;

6. To report promptly to the medical or nursing staff any unexpected problems or changes in your medical condition;

7. To inform the Study doctor or Study staff or of any concerns or problems with the care and treatment that you feel are not being adequately addressed;

8. To provide your own transportation to and from the Study site and to pay your own living expenses. Expenses that are covered by the Study will be explained to your before you begin to participate in the Study; and

9. To provide complete information so that contacts and communications to schedule visits and monitor health status can be maintained. This information should include: (1) your current address and phone number; (2) the names, addresses, and phone numbers of next of kin or persons to be notified in the event of an emergency; and (3) the names, addresses, and phone numbers of physicians responsible for your ongoing care, including your family physician and the physician(s) who referred you to the Study.

7. ARE THERE ANY OTHER OPTIONS? Your participation is voluntary so you have the right to decline to participate or to withdraw from this research Study at any time without any penalty or loss of benefits to which you would be entitled outside of the Study. Choosing not to participate will not affect the care you receive at Cedars-Sinai Health System. Your medical care will not be changed in any way as a result of this decision.

Study ID

: HS


: 10/1/2015 To: 9/30/2016


If you decide not to take part in this Study, you have other choices. For example: • you may choose to be treated following the usual clinical approach.

o Possible treatments that may be considered include the use of beta blockers, aspirin, diuretics, cholesterol lowering agents, anticoagulants, ACE inhibitors or calcium channel blockers and enrollment in a cardiac rehabilitation program.

o Depending on the degree of heart damage and effect on the subject's heart rhythm, the subject may be eligible for a pacemaker or implantable cardioverter-defibrillator. Subjects with severe heart failure may be eligible for devices that assist the heart’s blood pumping function. These devices are called cardiac assist devices.

• you may choose to take part in a different study at CSMC or elsewhere, if one is available

• you could decide not to be treated. • you may choose to pursue supportive or palliative care for your condition. Such care

is focused on reducing suffering and improving the quality of life of individuals with chronic or life-threatening illnesses. The primary intent of palliative care is not to cure a disease or to prolong life. Palliative therapy is focused primarily on managing symptoms.

Your Study doctor can provide information about your disease and the risks and benefits of other treatments. Please feel free to discuss your treatment for cardiomyopathy associated with DMD with your Study doctor. However, the specific medical or surgical management of your condition is determined by your primary care physician or cardiologist. 8. WILL MY INFORMATION BE KEPT CONFIDENTIAL? We will do our best to make sure that the personal information collected as part of this study is kept private. However, we cannot guarantee total privacy. A copy of your research consent and authorization forms may be filed in your electronic medical record at CSMC. Your personal information may be given out if required by law. If information from this study is published or presented at scientific meetings, your name and other identifiable personal information will not be used. Organizations that may look at and/or copy your medical records for research, quality assurance, and data analysis include: accrediting agencies, government and regulatory groups (such as Food and Drug Administration (FDA), Office for Human Research Protections (OHRP), etc.), safety monitors, companies that sponsor the study, and authorized representatives of the sponsor. You will be asked to sign a separate “Authorization Form” that outlines who your information may be shared with for the purposes of this Study and under what circumstances it may be shared. When possible, investigators will assign a unique code to your research information so that people who see the coded data will not be able to identify you. However, coding is not possible in some cases, such as when it will be necessary process payments to you for participation in the Study. Additional steps will be taken to ensure your privacy, such as storing your private information in a secure location where only authorized individuals, such as the Study doctor or Study staff, will have access to it.

Study ID

: HS


: 10/1/2015 To: 9/30/2016


The Study team will facilitate any required access to your records by authorized representatives of the Sponsor to verify the information collected for the Study. A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required by U.S. Law. This Website will not include information that can identify you. At most, the Website will include a summary of the results. You can search this Website at any time. 9. WHAT IF I BECOME ILL OR INJURED BECAUSE OF TAKING PART IN

THIS STUDY? Contact your Study doctor at once if you feel that you are ill or have been injured because of taking part in this Study. If it is a medical emergency, call 911 or go to an emergency room. Promptly notify your researcher of your situation at the phone number listed on page 1 of this consent form. Who pays for my research related illness or injury? A study-related injury or illness is a direct result of the use of CAP-1002, the infusion catheter or a procedure performed only as a part of the Study and is not part of your standard clinical medical treatment. If any injury or illness happens to you as a direct result of properly given Study product or properly performed procedures required by the Study, the Sponsor of this Study will reimburse for standard charges for actual and reasonable medical expenses incurred in treating any such injury or illness. You will not pay for the costs of care provided by Cedars-Sinai Health System or in any emergency room provided that you are being treated for a Study-related injury or illness. Cedars-Sinai may, however, ask for reimbursement where allowed from parties such as your health insurance carrier. If you choose to obtain medical care at a different medical facility for an injury or illness not related to the Study, you or your health plan may be responsible for the costs of that care. The Sponsor carries insurance to cover injuries to subjects participating in the Study directly resulting from the use of the Study product in accordance with the Study Protocol. Treatment may include first aid, emergency care and follow-up care, as needed. Payments will not be offered for other expenses (such as time off work, lost wages, childcare, etc.) You do not give up any legal rights by signing this form.

10. FINANCIAL CONSIDERATIONS Costs of Participation You and your insurance company will not be charged for procedures and tests performed because of your participation in this research Study. The costs of Study-related procedures and tests will be paid for by funds set aside for the conduct of the Study by the Sponsor. Some or all of the funding may have come from grants or loans received by the Sponsor. No funds have been set aside for any procedures not related to the Study. If you are randomized to receive CAP-1002, all procedures and tests performed because of participation in this Study will be paid for by funds set aside for the conduct of the Study by the Sponsor, with the exception of the following: In the event that, during your catheterization, your doctor discovers

Study ID

: HS


: 10/1/2015 To: 9/30/2016


that there is some physical reason you cannot receive the infusion, you will not receive CAP-1002 and you will no longer be in the Study. The angiogram will be paid for by the Study Sponsor. Any other treatment provided to you as a result of the finding of the angiogram is not Study-related and will not be covered by Study funds. You and/or your insurance will be responsible for any costs associated with treatment that is not Study-related, unless it is an injury or illness related to CAP-1002 or a procedure performed only as a part of the Study that is not part of your standard clinical medical treatment.

If you are randomized to receive usual care, you, or your insurance carrier if applicable, will be responsible for the costs of such care, except that Sponsor will pay for those tests, procedures and assessments that are required for the Study and are not part of usual care.

Any other medical visits and procedures you have outside of the Study due to other standard of care treatments or other health issues are billable to you or your insurance through normal hospital billing practices. Standard of care means necessary for the care of a medical issue as determined by your doctor and not necessary for this Study.

Compensation for Participating You will be paid $50 for the Week 2, Week 6, and Month 3visits. You will receive $100 for the screening visit, intracoronary infusion visit, and the visits at months six and twelve. The total amount you will receive if you complete the whole study is $550. These disbursements are intended to cover the costs required to complete these Study visits, such as transportation, parking and time. Necessary travel expenses (reasonable hotel, meals and fuel) and parking expenses may be reimbursed, depending on the individual circumstances. Study staff will contact the Sponsor to request reimbursement on a case by case basis. You will be paid for your visits after completion of each visit. If you do not complete the entire research Study, you will only be paid for those visits and procedures you do complete. You may be required to complete a W-9 Form (tax form where you provide your Social Security Number) in order to receive payment. The W-9 Form will be maintained by our accounting department at Cedars-Sinai. Although any amount of payment may be reportable (check with a tax professional if you have questions about your obligations), if total payment by Cedars-Sinai is $600 or more in a calendar year, a 1099 Form will be filed with the IRS in accordance with federal tax law. If you are a Cedars-Sinai employee, you should provide your employee identification number to the research team so that your payment can be appropriately processed through Payroll. For your own protection and to comply with tax laws, your payment for participation will be reported to the IRS together with other compensation you receive from Cedars-Sinai. Financial Interest in the Research A significant financial interest is a situation in which financial considerations have the potential to influence a person’s professional judgment. This Study has been designed to minimize the impact of the investigator’s financial interest. You are encouraged to ask the investigator to explain how the financial interest disclosed below will be managed. The Sponsor, Capricor, Inc., is providing the Study Drug (CAP-1002) for use in this Study. The Sponsor leases space at CSMC for its research facilities and also uses space at CSMC to manufacture the Study Drug.

Study ID

: HS


: 10/1/2015 To: 9/30/2016


Dr. Eduardo Marbán, who is the head of the CSMC Heart Institute, invented the methods used to grow and expand stem cells from heart biopsies which are the methods that were used in the development of the Study Drug. CSMC filed applications for patents regarding those inventions which have been licensed by the Sponsor. Dr. Eduardo Marbán and his wife, Linda Marbán, PhD, are both founders and shareholders of the Sponsor. Linda Marbán is the Chief Executive Officer (CEO) of the Sponsor and also has a part-time position at CSMC. Dr. Eduardo Marbán, Linda Marbán and the Sponsor could benefit financially if the Study Drug turns out to be commercially viable. Because of this potential conflict of interest, Dr. Eduardo Marbán: 1. Will disclose financial interest as part of any future publications and/or presentations. 2. Will not participate in initial recruitment of potential participants. 3. Will not participate in determinations regarding the severity and relevance of adverse events. 4. Will not obtain informed consent from potential subjects. 5. Will not participate in the screening and acceptance of potential research subjects. 6. Will not perform investigational procedures on enrolled subjects that go beyond clinical assessments completed by a treating physician as part of the ongoing management of a patient. Additionally, 1. A non-conflicted investigator will have control over the design and final analysis of the research, and will certify integrity of all aspects of the research, including the eligibility of potential subjects. 2. The study will be designed to incorporate measures that minimize potential bias, such as multiple sites, or objective endpoints. The Principal Investigator, Dr. Ronald Victor, has served as consultant for the Sponsor but has not received payment for these services. Similarly, co-investigator, Dr. Raj Makkar, serves as a consultant for the Sponsor but has not received payment for his services. CSMC has a financial interest in this study as follows:

CSMC has entered into two license agreements with the Sponsor with respect to intellectual property rights, some of which relate to the drug being tested in this Study.

CSMC has received consideration from Capricor pursuant to the two license agreements and may receive additional consideration in the future.

CSMC may be entitled to receive future royalties. CSMC is a shareholder in the Sponsor's parent company, Capricor Therapeutics, Inc. CSMC receives rent from Capricor in connection with its lease with the Sponsor.

11. WHAT IF I HAVE QUESTIONS OR PROBLEMS? Please contact one of the investigators listed on the first page of this form for questions or concerns about the research. If you have questions, problems, or concerns that you want to discuss with someone who is not associated with this Study, or want to offer suggestions or feedback, please contact:

Study ID

: HS


: 10/1/2015 To: 9/30/2016


Cedars-Sinai Human Research Protection Program (HRPP) Phone: (310) 423-3783 Email: [email protected] OR University of Southern California (USC) Health Sciences Institutional Review Board (IRB) Phone: (323) 223-2340 Email: [email protected]

The Cedars-Sinai HRPP and USC IRB have been established to protect the rights and welfare of research participants. You may also contact the Cedars-Sinai HRPP if you want to offer input or obtain information regarding the Study. 12. CONSENT PROVISIONS If you sign this form below, it means that: (1) You have taken the time to carefully read and understand the information presented in this informed consent form; you should discuss it with others, and if appropriate seek a second opinion to make an informed decision; (2) The information concerning the research Study and its involved procedures has been fully explained to you and your questions have been answered to your satisfaction; (3) You have received and understand all of the information you desire regarding your participation in the research Study; (4) You have considered the potential risks, any anticipated benefits and alternatives (and their relative risks and benefits) of participation, and will contact the Study doctor immediately if you experience any unexpected or unusual symptoms, or require other medical treatments that are necessary for you; (5) You are voluntarily agreeing to participate in this research Study, and understand that you do not have to participate and may withdraw from the Study at any time without penalty; (6) You understand that by consenting to participate in the research, you are not giving up any of your legal rights; (7) You understand that you have the right to be informed of significant new findings related to this research Study which may affect your willingness to continue participating in this Study; and (8) You have been provided with a copy of the “Experimental Subject’s Bill of Rights”, if applicable to this research Study, and have been provided with an opportunity to ask questions regarding the Bill of Rights. We will give you a copy of this signed and dated consent form and a signed copy of the Experimental Subject’s Bill of Rights.

Study ID

: HS


: 10/1/2015 To: 9/30/2016


SIGNATURE BY THE PARTICIPANT: Name of Participant (Print) Signature of Participant Date of Signature SIGNATURE BY THE SUBJECT’S PARENT/GUARDIAN (IF APPLICABLE) By providing my signature below, I consent and give permission for the participation of my child, , in the research Study described in this document. Name of child Parent/Guardian Name (Print) Signature Date of Signature SIGNATURE BY THE INVESTIGATOR: I have personally explained the research to the participant in non-technical terms, answered all questions, and attest that he/she freely consents to participate. The participant has been provided with the Experimental Subject’s Bill of Rights. Signature of the Investigator Who Obtained Consent Date of Signature

Study ID

: HS


: 10/1/2015 To: 9/30/2016


EXPERIMENTAL SUBJECT’S BILL OF RIGHTS

In accordance with California Health and Safety Code 24172, any person who is required to consent to participate as a subject in a research study involving a medical experiment or who is requested to consent on behalf of another has the right to:

1. Be informed of the nature and purpose of the experiment. 2. Be given an explanation of the procedures to be followed in the medical experiment, and

any drug or device to be utilized. 3. Be given a description of any attendant discomforts and risks to the subject reasonably to

be expected from the experiment. 4. Be given an explanation of any benefits to the subject reasonably to be expected from the

experiment, if applicable. 5. Be given a disclosure of any appropriate alternative procedures, drugs or devices that

might be advantageous to the subject, and their relative risks and benefits. 6. Be informed of the avenues of medical treatment, if any, available to the subject after the

experiment if complications should arise. 7. Be given an opportunity to ask any questions concerning the experiment or the procedure

involved. 8. Be instructed that consent to participate in the medical experiment may be withdrawn at

any time and the subject may discontinue participation in the medical experiment without prejudice.

9. Be given a copy of any signed and dated written consent form used in relation to the

experiment. 10. Be given the opportunity to decide to consent or not to consent to a medical experiment

without the intervention of any element of force, fraud, deceit, duress, coercion, or undue influence on the subject’s decision.

___________________________________________ ___________________________ Signature of Experimental Subject Date

Study ID

: HS


: 10/1/2015 To: 9/30/2016


SIGNATURE BY THE SUBJECT’S PARENT/GUARDIAN (IF APPLICABLE) By providing my signature below, I consent and give permission for the participation of my child, , in the research study described in this document. Name of child Parent/Guardian Name (Print) Signature Date of Signature Distribution instruction for researchers: The signed (i) Informed Consent form, (ii) Authorization for Use and Disclosure of Identifiable Health Information and (iii) "Experimental Subject’s Bill of Rights" (the latter required if the research study involves medical interventions)* should be distributed to: 1) Medical Chart 2) Research Participant 3) Pharmacy (if a drug study) 4) Principal Investigator’s research records (original)

Study ID

: HS


: 10/1/2015 To: 9/30/2016

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of 28

F

LO

WC

HA

RT

OF

PR

OC

ED

UR

ES

– For S

tud

ies that d

o not u

nd

ergo Med

icare Coverage A

nalysis (M

CA

) P

rocedure / Event

Screening Infusion

W

eek 2 W

eek 6 M

onth 3 M

onth 6 M

onth 12 (S

tud

y C

omp

letion)

Early

Term

ination

1

Research

Related

Proced

ures: Item

s, dru

gs and

services don

e for research p

urp

oses only.

Th

ese will b

e covered b

y the sp

onsor of th

e stud

y and

will N

OT

be b

illed to you

r insu

rance com

pany.

Study D

ay D

ay -30 to -1 D

ay 0 D

ay 14 (±3) D

ay 40 (±7) D

ay 90 (±7) D

ay 180 (±14) D

ay 360 (±30) A

s Needed

PR

E

PO

ST

Informed C

onsent X

Eligibility A

ssessment

X

X

Dem

ographics X

Medical H

istory X

X

Cardiac H

istory X

X

Concom

itant Medications

X

X

X

X

X

X

X

X

X

Vital S

igns X

X

X

X

X

X

X

X

X

Weight

X

X

X

X

12-Lead E

CG

X

X

X

X

X

X

X

X

X

Lim

ited Physical E

xamination

X

X

X

Cardiac P

hysical Exam

ination X

X

X

X

X

X

X

X

X

Cardiac M

RI

X

X

X

X

24-Hour A

mbulatory E

CG

via H

olter Monitor or Z

IO®

Patch

X

X

X

X

X

X

Clinical L

aboratory Tests

(includes Chem

istry, H

ematology, U

rinalysis) X

X

X

X

X

X

X

X

X

Serology

2 X

Osteopontin

X

X

X

X

X

X

X

ST

2 X

X

X

X

X

X

X

IL-10

X

X

X

X

X

X

X

Galectin-3

X

X

X

X

X

X

X

Exploratory B

iomarkers

X

X

X

X

X

X

X

HL

A

X

Study ID

: HS


: 10/1/2015 To: 9/30/2016

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Procedure / E

vent Screening

Infusion

Week 2

Week 6

Month 3

Month 6

Month 12

(Stu

dy

Com

pletion

)

Early

Term

ination

1

Research

Related

Proced

ures: Item

s, dru

gs and

services don

e for research p

urp

oses only.

Th

ese will b

e covered b

y the sp

onsor of th

e stud

y and

will N

OT

be b

illed to you

r insu

rance com

pany.

Study D

ay D

ay -30 to -1 D

ay 0 D

ay 14 (±3) D

ay 40 (±7) D

ay 90 (±7) D

ay 180 (±14) D

ay 360 (±30) A

s Needed

PR

E

PO

ST

DS

A

X

X

X

X

X

X

X

EL

ISpot

X

X

PU

L scale

X

X

X

X

X

X

6MW

T

X

X

X

X

X

X

Pediatric Q

L Inventory

X

X

X

X

X

X

PO

DC

I X

X

X

X

X

X

Spirom

etry X

X

X

X

X

X

Coagulation

X

Serum

Troponin &

CK

-MB

X

X

X

X

X

X

Intracoronary Infusion

X

Adverse E

vent Assessm

ent X

X

X

X

X

X

X

X

X

1 A

n early termination visit w

ill occur if you decide to leave the Study before com

pleting the entire 12 months. A

Cardiac M

RI w

ill be conducted provided the subject’s most

recent study-related Cardiac M

RI w

as conducted at least three months (i.e., 12 w

eeks) prior to the Early T

ermination V

isit. 2 Includes H

IV and hepatitis testing

Study ID

: HS


: 10/1/2015 To: 9/30/2016

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AP

PE

ND

IX B

: Detailed

Descrip

tion of C

omm

on M

edical P

rocedu

res Perform

ed for R

esearch P

urp

oses and

Associated

Risk

s T

he procedu

res listed below are often

performed as part of rou

tine care for a person

with

your con

dition. T

hey are bein

g repeated, or performed m

ore frequ

ently as part of th

is research. H

owever, th

e risks associated with

each procedu

re shou

ld be comparable to w

hat you

wou

ld experience even

if you w

ere u

ndergoin

g the procedu

re outside th

is research stu

dy.

Study P

rocedure R

elated Risks

Blood

draw

: A needle is placed in the vein in your arm

to draw

blood B

lood drawing m

ay cause some pain and has a sm

all risk of bleeding, bruising, or infection at the puncture site. T

here is also a small risk of

fainting. E

lectrocardiogram (E

CG

): abbreviated as EK

G or E

CG

– is a test that m

easures the electrical activity of the heartbeat using electrodes (disposable adhesive discs called “leads” w

ill be placed on the skin). Leads w

ill be placed on your chest, arm

s, and legs to measure the

electrical activity of your heart. It takes about five minutes

to place the leads and obtain the tracing. This test w

ill be perform

ed with every Study visit for a total of eight tim

es.

There’s no pain or risk associated w

ith having an electrocardiogram.

When the disposable adhesive discs are rem

oved from your skin, there

may be som

e minor skin discom

fort or irritation. You m

ay experience tem

porary discomfort (pulling on the skin/skin hair) during rem

oval of the patches. T

his hair may be shaved for patch placem

ent.

Intraven

ous (IV

) lines: Y

ou will receive the m

edications or contrast agent through an intravenous (IV

) line. An IV

line is a sm

all tube that is attached to a catheter and inserted by needle into a vein usually in your hand or arm

. Q

ualified medical professionals w

ill place IV lines for use

in this study.

IV lines are usually safe and w

ell tolerated and complications are rare,

but can include phlebitis (swelling of the vein) and infection. T

he IV

may com

e out accidentally or blood may leak around the line. If the IV

is not in the vein, m

edication or fluid can enter the surrounding soft tissues, and can be associated w

ith swelling, discom

fort, bruising and irritation. R

arely, a clot can develop in the IV line itself. If this

happens, the staff may rem

ove the old IV line and start a new

IV line.

There is also a sm

all risk of feeling lightheaded and fainting. M

agnetic R

esonan

ce Imagin

g (MR

I): A M

RI is a test

that uses a magnetic field and pulses of radio w

ave energy to m

ake pictures of your heart. This test can determ

ine w

hether there are any tumors and also provides

information about blood flow

and function in different regions of your heart. T

o increase the quality of these pictures, a contract agent (“dye”) w

ill be given by injection into a vein prior to the M

RI. D

uring the

You m

ay feel slightly anxious inside the scanner due to a fear of small

enclosed spaces (claustrophobia). Also, at tim

es, you may hear very

loud noises as the MR

I machine is taking pictures of your body. Y

ou m

ay be given headphones and may request ear plugs if you feel the

noise is too loud. At any tim

e, you may ask the technician to stop the

exam if you are unable to com

plete the exam. It is im

portant for you to advise the M

RI staff if you have had brain surgery for a cerebral

aneurysm (dilated blood vessel). Y

ou should also tell the staff if you

Study ID

: HS


: 10/1/2015 To: 9/30/2016

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Study P

rocedure R

elated Risks

procedure you will lie dow

n in a large donut-like looking m

agnet and we w

ill ask you to lie still on a table for the duration of the procedure (about 40-60 m

inutes). You

will be able to com

municate w

ith researchers all the time

and you will have a panic button to use if you w

ant to stop the procedure at any tim

e. You w

ill have this test at the screening visit and also at the 6 and 12-tw

elve month

visits for a total of 3 times during the S

tudy.

have implanted m

edical devices, such as pacemakers or im

plantable cardioverter-defibrillators, or m

etallic devices, shrapnel, or other metal,

such as metal in your eye, because if you have any possible m

etal in your body you cannot undergo an M

RI. T

he dye you will receive is

used routinely for MR

I exams. It contains a m

aterial called gadolinium.

The risks of contrast m

aterial are more clearly identified in a separate

section. (See C

ontrast Dye section)

Con

trast Dye: C

ontrast dye is used for the angiography and M

RI studies. T

his dye will help provide better im

ages of your heart. T

he dye will be injected into your vein

during the MR

I procedure and into the arteries of your heart during the infusion visit (if random

ized to CA

P-

1002).

The injection of the dye does not cause pain, but you m

ay feel discom

fort, tingling or warm

th in the lips, metallic taste in the m

outh, tingling in the arm

, nausea, or headache. These sym

ptoms occur in less

than 1% (less than 1 in 100) of people and go aw

ay quickly. Insertion of the needle to inject this dye m

ay also cause minor pain, bruising and/or

infection at the injection site. T

here may be an allergic reaction to contrast dye causing rash, itching,

hives, or wheezing, but the likelihood that this w

ill be severe is less than 1%

. You w

ill be assessed for any previous allergic reaction to contrast dye prior to procedures utilizing dye. P

re-medication w

ith antihistamine

and steroids may be used to for subjects w

ho have a history of sensitivity or allergy, according to the hospital’s protocol. Y

ou will be

closely monitored for any signs of allergic reaction and m

edically treated, if necessary. T

here is a possibility of developing abnormal function of the kidneys,

which is usually tem

porary. This is generally resolved by the natural

elimination of the contrast dye from

your system. T

o assist your body in counteracting these effects, you w

ill be kept fully hydrated. These

effects are most com

mon in people w

ho have evidence of preexisting abnorm

al kidney function. If your kidney function is significantly im

paired, as judged by a calculation called the creatinine clearance, the dose and type of contrast dye m

ay need to be adjusted. If your kidney function becom

es severely impaired, you m

ay not be able to have tests that require contrast dye.

Study ID

: HS


: 10/1/2015 To: 9/30/2016

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Study P

rocedure R

elated Risks

Certain contrast agents used in M

RI are associated w

ith a rare but serious side effect called nephrogenic system

ic fibrosis (NS

F) in

patients with kidney disease. N

SF

may result in fatal or debilitating

fibrosis – a thickening of the skin that limits the range of m

otion and joint pain; internal organs (lungs, heart, liver) can be affected too. S

igns and sym

ptoms of N

SF

include burning, itching, swelling, scaling,

hardening and tightening of the skin; red or dark patches on the skin; stiffness in joints w

ith trouble moving, bending or straightening the

arms, hands, legs or feet; pain in the hip bones or ribs; or m

uscle w

eakness. Your doctor w

ill screen you to see how w

ell your kidneys are w

orking first before administering any contrast agent during the M

RI.

24 -H

our E

CG

Mon

itoring: D

uring this test, electrodes (either w

ith wires or a patch) are placed on your chest,

over the heart, to record its electrical activity. They w

ill be attached to a recorder w

hich will record all of the heart

beats and electrical activity for 24 hours. You w

ill be provided w

ith a notebook to write dow

n any symptom

s you experience and the tim

es when they occur. T

his test w

ill be done at the screening, after infusion, and at the 6 w

eek, 6 month and 12 m

onth visits. This test w

ill be perform

ed 5 times during your participation in this S

tudy.

Please see the R

elated Risks section associated w

ith “Electrocardiogram

(E

CG

).” Although painless, you w

ill need to carry a monitor in a pocket

or in a small pouch w

orn around your neck or waist. T

here are no risks or side effects.

Ph

ysical Exam

: Includes height, weight, vital signs (heart

rate and blood pressure). T

here are no physical risks associated with these procedures.

At every S

tudy visit, your Study doctor w

ill perform a brief physical

examination focusing on your heart. A

limited general physical

examination w

ill also be performed at the beginning and at the end of

the Study. Y

our temperature, heart rate, blood pressure and breathing

rate as well as w

eight will be m

easured. Your w

eight will be m

easured at the beginning of the S

tudy, Month 6, and M

onth 12 (or if you decide to w

ithdraw early from

the Study). T

he Study staff w

ill review your

medications and ask you specific questions about any unusual

symptom

s or any illnesses you have had.

Study ID

: HS


: 10/1/2015 To: 9/30/2016

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Study P

rocedure R

elated Risks

Con

comitan

t Med

ications: Y

ou will be asked about your

previous and current medications that you take.

There are no physical risks associated w

ith these procedures.

Med

ical History R

eview: Y

ou will be asked about your

medical and surgical history w

ith attention to smoking and

alcohol habits and your physical activity.


ith this procedure.

6-Min

ute W

alk T

est (6MW

T): Y

ou will be asked to

perform this test only if the S

tudy doctor believes that it is reasonable for you to do so. Y

ou will be asked to w

alk for 6 m

inutes along a designated pathway (a track in the

hospital hallway) w

hile being observed by study personnel. Y

our heart rate and blood pressure will be

recorded before and after the test. We w

ill also measure

the distance that you are able to walk during the 6

minutes. A

fter the test, you will also be asked a few

questions. T

he test and assessments w

ill take about 10-15 m

inutes, but no more than 30 m

inutes total. This test w

ill be perform

ed at the screening visit as well as the 6 m

onth and 12 m

onth visits for a total of 3 times.

There is a rare possibility of fainting, w

hile you perform the 6 M

inute w

alk test. You m

ay develop shortness of breath (difficulty breathing), your heart rate m

ay be faster than usual, the level of oxygen in your blood m

ay decrease, and/or you may develop pain or soreness in your

legs. Please note that all m

edical procedures will be done in the

presence of the study Investigator and research team in order to

minim

ize the occurrence of such untoward events. Y

ou can choose to stop at any tim

e during the test.

Urin

e Collection

: You w

ill be asked to provide a small

urine sample, about tw

o to three tablespoons, to be analyzed. T

he laboratory will look at the urine for color

and concentration and to see if cells, urine crystals, m

ucus, bacteria or other germs are present. T

his test will

be performed w

ith every Study visit.

No risks associated w

ith this procedure.

Blood

Stu

dies: A

pproximately 6-13 teaspoons of blood

will be obtained from

a needle placed in your vein at screening, infusion, and during each of the follow

-up visits unless otherw

ise specified below. T

hese will be used

to measure your blood counts and liver and kidney

function at these times. T

he following blood tests w

ill be perform

ed during the course of the Study: •

Chem

istry: electrolytes, kidney and liver function test. •

Hem

atology (Blood C

ounts): i.e., white blood cell

Blood draw

ing may cause som

e pain and carries a small risk of

bleeding, bruising, or infection at the puncture site. There is a sm

all am

ount of discomfort w

hen a needle is inserted to withdraw

blood from

a vein. Occasionally, a sm

all accumulation of blood (hem

atoma) or

infection may occur at the point of insertion. T

here is also a small risk

of fainting. All blood sam

ples will be obtained by a trained technician

and performed in a m

anner to minim

ize the likelihood of bruising and bleeding.

Study ID

: HS


: 10/1/2015 To: 9/30/2016

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Study P

rocedure R

elated Risks

count, hemoglobin, platelets

• H

epatitis •

Donor S

pecific Antibody (D

SA

) test: looks to see w

hat antibodies are in your blood •

Hum

an Leukocyte antigen (H

LA

) typing: a “fingerprint” of your body’s im

mune system

•

EL

ISpot A

ssay: looks at your blood cells’ imm

une response to C

AP

-1002 (takes requires an extra two

tablespoons of blood) •

Cardiac E

nzymes (T

roponin I and CK

-MB

): measure

enzymes in your blood that are present w

hen your heart m

uscle is not getting enough oxygen •

Osteoponin and G

alectin-3: factors whose

measurem

ents are related to increased work being

done by your heart and presence of heart failure •

ST

2 and Interleukin -10 (IL-10): factors w

hose m

easurements are related to im

mune response, as w

ell as cell m

igration and attachment

In addition to the blood studies that are necessary for the S

tudy, blood for exploratory biomarkers w

ill be taken if you provide consent for this sub-study. E

ach blood draw takes about 5 to 10 m

inutes. A

pproximately 11 blood draw

s will be done at specified

intervals during the 13 months of your participation in this

Study.

Qu

estionn

aires: You w

ill be asked to complete

questionnaires during Study visits. Y

ou will be asked

questions to evaluate your quality of life and how w

ell you are functioning w

ith your heart illness. We think it

should take about 50 minutes to com

plete the

If you feel uncomfortable or em

barrassed answering any question, you

may skip it. T

he questionnaire will be labeled w

ith a unique study num

ber that will link your identity so that only the research team

can recognize you. If you don’t understand a question, study staff w

ill be available to assist you.

Study ID

: HS


: 10/1/2015 To: 9/30/2016

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questionnaires. •

The P

erformance of U

pper Lim

b (PU

L) S

cale is an assessm

ent of the strength and mobility of the arm

using 22 sm

all tasks related to the activities of daily living. It w

ill take about 20 minutes to

complete this assessm

ent. •

The P

ediatric Quality of L

ife inventory (PedsQ

L,

including cardiac module) is an assessm

ent that w

ill provide information about physical,

emotional, social and school functioning. It w

ill take about 10 m

inutes to complete this assessm

ent. •

The P

ediatric Outcom

es Data C

ollection Instrum

ent (PO

DC

I) is an 83 to 86 item, self-

administered questionnaire that m

easures functional abilities and quality of life. It w

ill take about 20 m

inutes to complete this assessm

ent. H

IV T

esting: A negative H

IV test is required for your

participation in this research. The H

uman

Imm

unodeficiency Virus (H

IV) m

ay lead to a disease know

n as AID

S, w

hich weakens the body’s im

mune

system, m

aking it susceptible to infections.

If your test is positive, you will be told and at that point you should

discuss the many H

IV treatm

ent options available with your prim

ary physician. If you test positive for H

IV, your nam

e and test results will

be reported to the local and state health departments in accordance w

ith C

alifornia law.

Dem

ograph

ic Inform

ation: Y

ou will be asked about

your age, gender, race, ethnicity


ith these procedures.

Infu

sion of C

ells: After you have com

pleted screening, the inform

ation obtained will be review

ed to make sure

that you are still eligible to participate in the Study. If you

continue to meet the criteria required for the S

tudy, you w

ill be randomized to receive C

AP

-1002 or usual care. If you are random

ized to receive CA

P-1002, you w

ill be scheduled for the infusion procedure and then brought to the cardiac catheterization laboratory to undergo a cardiac catheterization procedure sim

ilar to the opening of arteries

Cardiac catheterization and A

ngiography: T

here may be som

e bruising or discomfort at the site w

here an incision is m

ade to insert the catheter into your artery. Serious complications,

however, can occur including death, stroke, dam

age to the heart muscle

(heart attack), the need for emergency cardiac surgery, chest pain, low

blood pressure, blood loss requiring a transfusion, changes in heart rate or rhythm

requiring treatment, changes in breathing requiring treatm

ent, injury or irritation to blood vessels that could require surgical repair, infection or the developm

ent of kidney dysfunction or failure. The risk

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: 10/1/2015 To: 9/30/2016

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with a balloon and stent (a very sm

all cylindrical wire

mesh) w

hen people have blocked arteries. How

ever, rather than opening an artery and placing a stent inside, C

AP

-1002 will be injected into three cardiac territories.

Dye w

ill be injected into the arteries in your heart and, if they are open, C

AP

-1002 will be infused through the

catheter. If, at the time of cardiac catheterization, a

technical issue arises or there is a physical reason the infusion cannot take place, you w

ill not receive CA

P-1002

and you will be rem

oved from the S

tudy.

of a major com

plication from cardiac catheterization is less than 2 out

of 100 subjects on average. How

ever, you may be at higher risk given

your heart condition. Less serious but m

ore comm

on risks (it might

happen about 1% of the tim

e) include bleeding or blood vessel injury w

here the catheter is inserted through the skin into the artery. If this occurs, treatm

ent might require a longer hospitalization, blood

transfusion, or repair of the blood vessel under the skin. C

hest Pain or P

ressure: During the infusion, it is not uncom

mon to feel

some chest pressure or discom

fort. The discom

fort is usually temporary,

lasting only for a couple of minutes. Y

our electrocardiogram and blood

pressure will be continuously m

onitored during the infusion. The

infusion will be stopped if you experience severe chest discom

fort that lasts longer than three m

inutes after completion of the cell infusion. A

selective angiography (x-ray) is perform

ed at the end of the infusion to determ

ine if each artery has good blood flow.

Dye: Y

ou may feel a w

arm, flushed feeling w

hen the dye is injected or an allergic reaction to the dye causing nausea, vom

iting or rash. D

rug Side E

ffects: There m

ay be side effects related to drugs that will

be used during the infusion or testing procedures. In particular, the follow

ing drugs will be used w

ith the CA

P-1002 infusion:

• H

eparin: Blood thinner used before the cell infusion; side effects

include reddening of the skin, hematom

a (localized collection of blood), injection site sore, heparin-induced throm

bocytopenia (low platelet

count), mild pain, local irritation.

• N

itroglycerin: Used to treat or prevent chest pain. It w

orks by relaxing the arteries w

hich increases the blood and oxygen to the heart. W

e use nitroglycerin in CA

P-1002 to open up the heart arteries so C

AP

-1002 can get into your heart tissue m

ore easily. Side effects include low

blood pressure, headache, dizziness, lightheadedness and/or fainting.

Sp

irometry: Y

ou will be asked to perform

a simple test

used to assess how w

ell your lungs work by m

easuring how

much air you inhale, how

much you exhale and how

quickly you exhale. T

his test will be perform

ed at the

Spirom

etry is a low risk procedure and has few

side effects. During the

test, some patients m

ay experience dizziness. The forced expiratory

maneuver causes an increase in the pressure in the chest, abdom

en, head, and eyes. In general, patients w

ho have recently (e.g., less than six

Study ID

: HS


: 10/1/2015 To: 9/30/2016

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screening visit as well as the 6 w

eek and 3, 6 and 12 m

onth visits for a total of 5 times.

weeks) had abdom

inal, intracranial, or eye surgery or a pneumothorax

should not perform spirom

etry, although data are limited.

Spirom

etry requires exertion and should be avoided in patients with

unstable angina or a recent myocardial infarction.

Rarely, perform

ance of a forced expiratory maneuver w

ill precipitate acute bronchoconstriction. T

his seems m

ore likely to occur when a

patient's asthma or C

OP

D is poorly controlled. T

reatment includes

administering inhaled albuterol and supplem

ental oxygen.

Study ID

: HS


: 10/1/2015 To: 9/30/2016

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