update on therapies: clinical trials timothy pm whelan assistant professor of medicine medical...
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Update on Therapies:Clinical Trials
Timothy PM WhelanAssistant Professor of Medicine
Medical Director, Interstitial Lung Disease ProgramUniversity of Minnesota
Outline Pathogenesis of pulmonary fibrosis Targets of treatment Measuring safety and efficacy of Rx Recent and current clinical trials Summary
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Pulmonary Fibrosis Scarring of the lungs produced by
collagen deposition Once scar is well established, disrupts
normal architecture of the lung Result: oxygen from the air does not
transfer into the blood stream normally
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Microscopic injury to the lung
Focal fibroblast proliferation
Collagen deposition
Return of normal lung architecture
Normal Lung Repair
Dissolution of the scaffolding
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Dissolution of the scaffoldingPersistence of collagen
scar
Microscopic injury to the lung
Focal fibroblast proliferation
Collagen deposition
Abnormal transfer of oxygen into the blood stream
Cause of Pulmonary Fibrosis
Recurrent microscopic injury
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Treatment Options Stop the cycle of recurrent injury
• Avoidance of known risk factors– Occupational exposures– Tobacco– Organic and inorganic dust exposures– Prevent infections: influenza, pneumococcus
• Treatment of medical conditions associated with development of fibrosis
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Treatment Options Stop continued deposition of collagen
• Affect mechanisms known to activate the fibroblast
• Increase removal of fibroblasts
• Boost the immune system?
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Treatment Options There are no proven medical therapies
for the treatment of Idiopathic Pulmonary Fibrosis
Future successful treatment relies on well designed clinical trials
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Clinical Trials Research protocols in human subjects Designed to answer a specific question Observational Trials
• Large groups of people in natural setting Interventional Trials
• Investigate experimental treatment effects• Several phases or steps in drug
development
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Phase IA new drug or treatment tested in a small
group of people for the first time• evaluate its safety
• determine a safe dosage range
• identify side effects
• may include healthy subjects
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Phase IIControlled clinical studies
• Evaluate the effectiveness of the drug for a particular indication or indications
• Tested in patients with the disease or condition under study
• Determine the common short-term side effects and risks.
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Phase IIIExpanded controlled and uncontrolled
trials after preliminary evidence suggesting effectiveness of the drug• gather additional information to evaluate
the overall benefit-risk relationship of the drug
• provide an adequate basis for physician labeling
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Phase IVPost-marketing studies
• Delineate additional information including the drug's risks, benefits, and optimal use.
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Trial Design Basics Hypothesis
• Primary versus secondary endpoints “Power”
• Ability of study to determine a difference
• Assumptions made by researchers– Number of patients enrolled– Number of events that are expected to occur– Estimation of treatment effect of intervention
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Trial Design Basics Inclusion criteria
• Specific disease process
• Age, test results, symptoms Exclusion criteria
• Concomitant illnesses
• Known interactions with interventions
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Trial Design BasicsControl Group Placebo
• Inactive compound Current standard regimen
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BenefitsWell-designed and well-executed clinical trials
allow eligible participants to: Play an active role in their own health care. Gain access to new research treatments
before they are widely available. Obtain expert medical care at leading health
care facilities during the trial. Help others by contributing to medical
research.www.clinicaltrials.gov
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Risks There may be unpleasant, serious or even
life-threatening side effects to experimental treatment.
The experimental treatment may not be effective for the participant.
The protocol may require more of their time and attention than would a non-protocol treatment, including trips to the study site, more treatments, hospital stays or complex dosage requirements.
www.clinicaltrials.gov
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Trial Design Basics Informed Consent
• Process by which study participants are fully informed as to specific risks/benefits of a particular protocol
• Process does not stop once enrolled but continues throughout the study period
• Consent within a study is voluntary and can be withdrawn at any point
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Clinical Investigations - IPFPhase I FG-3019 – completedPhase II Bosentan (Tracleer®) – enrollment closed Etanercept (Enbrel®) – enrollment closed Imatinib (Gleevec®) – enrollment ongoing Pirfenidone – completedPhase III Gamma Interferon-1b (Actimmune®) -- ongoing
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Summary Pulmonary fibrosis results from the
normal healing process going astray Treatment options once pulmonary
fibrosis develops are limited Clinical trials involve multiple phases of
investigation
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Summary Multiple promising drug therapies are
already under investigation Well designed, large clinical trials are
the key to obtaining answers for the future
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Resources to learn more www.clinicaltrials.gov www.coalitionforpf.org www.thoracic.org/patiented/patedmaterials.asp
www.lungusa.org University of Minnesota Center for
Advanced Lung Disease Registry of Interested Persons
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Resources to learn more University of Minnesota Center for
Advanced Lung Disease Registry of Interested Persons• Contact Jenny or Joslyn: (612) 625-7741
• Toll Free: 1-800-646-9255
• E-mail: bieveØØ[email protected]
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