horizon scanning p upate august 2012 - keele … · feedback from a pilot horizon scanning exercise...

Written by Nadia Corp for © Arthritis Research UK 2012

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HORIZON SCANNING: PAEDIATRIC RHEUMATOLOGY

UPATE AUGUST 2012

The object of these Horizon Scanning reports is to highlight recently completed and ongoing clinical trials, research recommendations and new and emerging health technologies. After feedback from a pilot Horizon Scanning exercise and following consultation with the MCRN/ARC Paediatric Rheumatology CSG lead, these Horizon Scanning reports only highlight ongoing clinical trials or those completed since January 2010. This follow up report includes trials registered since February 2012 for seven Topic Specific Groups (TSGs): Bone Health; Juvenile Dermatomyositis; Juvenile-Idiopathic Arthritis and JIA-associated Uveitis; Juvenile-onset Systemic Lupus Erythematosus; Non-inflammatory Musculoskeletal Disorders; Scleroderma and Vasculitis. Details of all material included in this report are shown in the appendix, sorted according to TSG. Further details of each study can be obtained via the links given to the relevant webpage.

CONTENTS

SEARCH METHODOLOGY 2 RESULTS 3 ABBREVIATIONS 4 APPENDIX: CLINICAL TRIALS 5

A1. Bone Health……………………………………………………………………………………………. 5 A1a: Calcinosis, Hyper- & Hypo-Calcaemia 5 A1b: Dysplasia & McCune Albright syndrome 5 A1c: Osteogenesis imperfecta 5 A1d: Osteopetrosis 5 A1e: Osteoporosis & Osteopenia 6 A1f: (Juvenile) Paget’s disease 8 A1g: Rickets & Hypophophatasia 8

A2. Juvenile Dermatomyositis………………………………………………………………………. 8 A3. Juvenile Idiopathic Arthritis and JIA-associated Uveitis………………………………… 9 A4. Juvenile-onset Systemic Lupus Erythematosus……………………………………….. 12 A5. Non-inflammatory Musculoskeletal Disorders……………………………………….. 14

A5a: Chronic pain syndrome, Complex regional pain syndrome & Fibromyalgia 14 A5b: Hypermobility, Joint hypermobility syndrome & ehlers-Danlos 14

A6. Scleroderma……………………..…………………………………………………………………… 15 A7. Vasculitis……………………………………………………………………………………………….. 15

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SEARCH METHODOLOGY

Clinical Trials Databases Searched

Australian New Zealand Clinical Trials Registry (ANZCTR)

ClinicalTrials.gov, US

German Clinical Trials Register (DRKS)

ISRCTN Register, UK

University Hospital Medical Information Network (UMIN), Japan

Japan Medical Association Center for Clinical Trials Register (JMA-CTR)

Japan Pharmaceutical Information Center Clinical Trials Register (JAPIC)

MRC Clinical Trials Unit, UK

The Netherlands National Trial Register (NTR)

UKCRN Portfolio Database, UK

World Health Organization International Clinical Trials Registry Platform (WHO ICTRP), to

include trials from the following registers:

o Chinese Clinical Trial Register (ChiCTR) o Clinical Research Information Service (CRiS), Republic of Korea o Clinical Trials Registry - India (CTRI) o Cuban Public Registry of Clinical Trials (RPCEC) o EU Clinical Trials Register (EU-CTR) o Iranian Registry of Clinical Trials (IRCT) o Pan African Clinical Trial Registry (PACTR) o Sri Lanka Clinical Trials Registry (SLCTR)

Keywords searched Keywords and phrases were used separately or in combination; truncation was used where possible/applicable.

Bone health: Calcinosis, Hypercalc[a]emia, Hyperphosphatasemia, Hypocalc[a]emia, Hypophosphatasia, Juvenile Paget’s disease, McCune Albright syndrome, Osteop[a]enia; Osteogenesis imperfecta, Osteopetrosis, Osteoporosis (juvenile idiopathic, glucocorticoid-induced/steroid-induced, disuse, pseudoglioma syndrome), Polyostotic fibrous dysplasia, Rickets (vitamin D deficiency, hypophosphataemic; pseudo-D deficiency; hereditary vitamin D resistant rickets), Skeletal dysplasia; Fracture (spinal/vertebral);

Dermatomyositis;

JIA, Juvenile idiopathic arthritis, juvenile rheumatoid arthritis, juvenile chronic arthritis, Oligoarticular juvenile arthritis, Pauciarticular juvenile arthritis, Polyarticular juvenile arthritis, Still's disease, JIA associated uveitis, Idiopathic uveitis, Autoimmune uveitis;

[Juvenile-onset] systemic lupus erythematosus, SLE, lupus nephritis;

Non-inflammatory: Chronic pain syndrome, Complex regional pain syndrome, Ehlers-Danlos, Fibromyalgia, Hypermobility, Joint Hypermobility Syndrome;

Scleroderma, Systemic sclerosis, Morphea, En coup de sabre, Juvenile localised scleroderma, Juvenile systemic sclerosis, Linear scleroderma, Facial hemiatropy; Parry Romberg;

Vasculitis, Kawasaki Disease, Mucocutaneous Lymph Node Syndrome, Behcet’s Syndrome, Wegener’s Granulomatosis, Microscopic Polyangiitis (MPA), Microscopic Polyarteritis,

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Polymyalgia rheumatic, Renal limited vasculitis, Cryoglobulinaemic vasculitis, Cogan’s syndrome, Takayasu’s Arteritis, Churg-Strauss Syndrome, Polyarteritis Nodosa, ANCA associated vasculitis, Henoch Schonlein purpura;

Child, Children, Childhood, Adolescent, Juvenile, Paediatric. Date limits Trials registered since February 2012 are included in the feedback and include any clinical trials ongoing or completed since January 2010. Age limits Studies involving individuals of 181 years of age and under were included in the report.

RESULTS

A total of 40 completed or ongoing clinical trials were identified across the seven topic areas included within paediatric rheumatology. These are tabulated in the appendix divided into sections:

A1: Bone Health (n = 9);

A2: Dermatomyositis (n = 0);

A3: Juvenile idiopathic arthritis and JIA-associated uveitis (n = 12);

A4: Juvenile-onset systemic lupus erythematosus (n = 8);

A5: Non-inflammatory (n = 2);

A6: Scleroderma (n = 1);

A7: Vasculitis (n = 8). For clarity each section is subdivided according to type of intervention: behavioural, education & exercise including physiotherapy; device; drug including biologics; procedure; other interventions including CAM; and no intervention, observational. Within each division, studies have been classified according to age group involved: ≤18 years (child) or all age groups (child and adult (including senior)) or age group unknown, and then arranged in descending chronological order of anticipated completion-date. (Trials where the end date was not specified are included based update the last update status e.g. recruitment complete etc, and follow-up time points if applicable.) Unless otherwise stated in the table trials involve participants of both genders. Each clinical study has a weblink which can be followed for further details. Where there was uncertainty regarding whether a study should be included or not (usually due to its focus), the decision aired on the side of caution and the trial was included in the feedback.

1 with the exclusion of studies where the lowest age limit is 18 years of age.

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ABBREVIATIONS

Adt Adult (18-65 years) ANCA Anti-neutrophilic Cytoplasmic Antibody Child Child (birth-17 years) Comp Completed CT Controlled trial CT ID Clinical Trials Identifier F-only Females only Grp Group mo Months n Enrollement N/K Not known NR Not recruiting RCT Randomized controlled trial. Rec Recruiting Recruit Recruitment Sen Senior (66+ years) SLE Systemic Lupus Erythematosus

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FULL TEXT APPENDIX

SECTION B: CLINICAL TRIALS Clinical trials identity number (CT ID): Prefix of ACTRN denotes Australian New Zealand Clinical Trials Registry; ChiCTR - Chinese Clinical Trial Register; CTRI - Clinical Trials Registry, India; DRK – German clinical Trials Register; NCT - National Clinical Trials Identifier; IRCT - Iranian Registry of Clinical Trials; ISRCTN - International Standard Randomized Controlled Trial Number; JapicCTI - Japan Pharmaceutical Information Center Clinical Trials; JMA - Japan Medical Association Center for Clinical Trials Register; KCT - Clinical Research Information Service (CRiS), Republic of Korea; NTR – Nederland Trial Register; PACTR - Pan African Clinical Trial Registry; RPCEC - Cuban Public Registry of Clinical Trials; SLCTR - Sri Lanka Clinical Trials Registry; UKCRN – UK Clinical Research Network; UMIN – University Hospital Medical Information Network. Note: Where no end date was given the following were used: completion date for primary outcome measure – italics; last update – preceeded with a ?; start date + final timepoint of outcomes – preceeded with a >.

A1: BONE HEALTH

A1A: CALCINOSIS, HYPER- & HYPO-CALCAEMIA No new clinical trials identified

A1B: DYSPLASIA & MCCUNE-ALBRIGHT SYNDROME No new clinical trials identified

A1C: OSTEOGENESIS IMPERFECTA No new clinical trials identified

A1D: OSTEOPETROSIS No new clinical trials identified

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A1E: OSTEOPOROSIS & OSTEOPENIA

Title Phases: trial design (control) CT ID

Interventions Conditions Recruit n Age (Grp)

Start Date

End Date

Sponsors URL

Behavioural, education & exercise including physiotherapy and manual therapy

≤18 years

Effects of Assistive Standing on Bone Mineral Density in Immobilized Children Non-randomized, parallel assignment, efficacy study DRKS00004289

Alternating periods of 0% body weight on one leg and 25% body weight on other leg; 25% body weight equally on both legs

Non-ambulatory children with osteoporosis or osteopenia

Comp 16 4-9 years

Oct-08 Oct-11 New Jersey Institute of Technology, USA

https://drks-neu.uniklinik-freiburg.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00004289

Vibration in Boys with a History of Fracture Observational: Prospective, cohort study UKCRN ID 12385

Vibration therapy Fracture history Active 24 9-12 years

Child

M-

only

N/K May-13 Sheffield Children's Hospital

http://public.ukcrn.org.uk/Search/StudyDetail.aspx?StudyID=12385

Drugs including biologics and injections

≤18 years

Severe Decrease of Growth Velocity in Children With Anorexia Nervosa.Therapeutic Trial of Growth Hormone Phase 2/3: RCT (placebo), efficacy study NCT01626833

SOMATROPINE*: Norditropine® simplexx®; Placebo

Anorexia Nervosa; Catch- Down or Even an Interruption of Growth; Delayed Puberty; Osteopenia With Failure of Acquisition of Bone Mass

Not yet Rec

20 8-17 years

Child

Sep-12 Sep-16 Assistance Publique - Hôpitaux de Paris; Novo Nordisk

http://ClinicalTrials.gov/show/NCT01626833

A Study of Odanacatib When Administered to Adolescents Treated With Glucocorticoids (MK-0822-066) Phase 1: RCT (placebo), pharmacokinetics/dynamics study NCT01630616

Odanacatib; Placebo Osteoporosis Not yet Rec

16 2-18 years

Child Adt

Aug-12 Jul-13 Merck http://ClinicalTrials.gov/show/NCT01630616






http://clinicaltrials.gov/show/NCT01626833


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All age groups

Growth Hormone for Osteoporosis Pseudoglioma Syndrome Single group assignment, safety/efficacy study NCT01614171

Human recombinant growth hormone

Osteoporosis Pseudoglioma Syndrome

Not yet Rec

10 ≥4 years

Child Adt Sen

Jul-12 Jul-14 University of Maryland; Children's Hospital of Philadelphia


Device

≤18 years

Replacing Spine Radiographs with Dexa Observational: Prospective cohort study UKCRN ID 12717

DEXA; X-ray Children undergoing spinal imaging

Active 250 5-16 years

Child

N/K Apr-13 Sheffield Children's Hospital


Dietary including supplements

≤18 years

Dose Effects of SCF on Calcium Metabolism and GI Microflora in Adolescents RCT (placebo), pharmacokinetics study NCT01660503

0 grams SCF; 10 grams SCF; 20 grams SCF

Osteoporosis Rec 30 9-13 years

Child

F-

only

Jun-12 Dec-13 Purdue University; Tate and Lyle Ingredients Americas LLC


No intervention: observational

≤18 years

Prospective fracture study in children and adolescents with chronic inflammatory and/or disabling conditions Observational: prospective, cohort study UKCRN ID 12292

Chronic inflammatory; Disabling conditions

Active 330 5-18 years

Child

N/K Mar-13 Birmingham Children's Hospital








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A1F: (JUVENILE) PAGET’S DISEASE No new clinical trials identified

A1G: RICKETS & HYPOPHOPHATASIA



Start Date

End Date

Sponsors URL


All age groups

Sunlight Exposure and Vitamin D Status of Children of South Asian Ethnicity Living in the UK Observational: Prospective cohort study UKCRN ID 12544

Vitamin D status Active 125 Child N/K Mar-14 Salford Royal NHS Foundation Trust


A2: JUVENILE DERMATOMYOSITIS No new clinical trials identified



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A3: JUVENILE IDIOPATHIC ARTHRITIS AND JIA-ASSOCIATED UVEITIS



Start Date

End Date

Sponsors URL


≤18 years

Efficacy of Web-based Pain Self-management for Adolescents With Juvenile Idiopathic Arthritis Phase 3: RCT (active), efficacy study NCT01541917

Web-based coping skills training; Online disease education

Juvenile Idiopathic Arthritis

Not yet Rec

360 12-18 years

Child Adt

Jul-12 Jun-15 Children's Mercy Hospital Kansas City; National Institute of Arthritis and Musculoskeletal and Skin Diseases


An Internet-based Self-management Program for Adolescents With Arthritis RCT (active), efficacy study NCT01572896

Taking Charge: Managing JIA Behavioral: Standard Medical Care and JIA Resource Center

Arthritis, Juvenile Idiopathic

Rec 294 12-18 years

Child Adt

Apr-12 Mar-15 The Hospital for Sick Children



≤18 years

Open-label Safety and Pharmacokinetic Study of DUEXIS® (Ibuprofen and Famotidine) Tablets in Juvenile Idiopathic Arthritis Phase 4: Single group assignment, safety study NCT01563185

800 mg ibuprofen/26.6 mg famotidine


Rec 30 10-17 years

Child

Apr-12 Oct-13 Horizon Pharma, Inc.; Pediatric Rheumatology Collaborative Study Group


Pediatric Arthritis Study of Certolizumab Pegol Phase 3: Single group assignment, safety/efficacy study NCT01550003

Certolizumab Pegol (CZP)

Juvenile Idiopathic Arthritis (JIA)

Rec 125 2-17 years

Child

Mar-12 Dec-16 UCB, Inc. http://ClinicalTrials.gov/show/NCT01550003





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An Open-Label Extension of the Dose Finding Study (DSC/08/2357/36) in Patients With Poly Juvenile Idiopathic Arthritis (JIA) Single group assignment, safety study NCT01557452

Givinostat Juvenile Idiopathic Arthritis

Rec 3 2-18 years

Child Adt

Dec-11 Dec-15 Italfarmaco; Parexel


An Extension Study to WA19977 in Patients With Active Polyarticular-Course Juvenile Idiopathic Arthritis Phase 3: Single group assignment, safety/efficacy study NCT01575769

RoActemra/ Actemra (tocilizumab)


Rec 45 ≥2 years

Child Adt Sen

Jan-12 Jun-15 Hoffmann-La Roche


Tocilizumab in the Management of Juvenile Idiopathic Arthritis Associated Uveitis Phase 1/2: Single group assignment, safety/efficacy study NCT01603355

Tocilizumab Juvenile Idiopathic Arthritis Associated Uveitis

Not yet Rec

5 2-17 years

Child

Jul-12 Dec-15 Oregon Health and Science University; Eric B. Suhler; Genentech


A Safety Study of VIMOVO in Adolescents With Juvenile Idiopathic Arthritis (JIA) Phase 4: Single group assignment, safety study NCT01544114

VIMOVO Juvenile Idiopathic Arthritis (JIA)

Rec 60 12-16 years

Child

Apr-12 Jun-13 AstraZeneca http://ClinicalTrials.gov/show/NCT01544114

All age groups

How should we educate young people to help them make decisions about biologic therapies? Observational: qualitative study UKCRN ID 12389

Biologic therapies

Inflammatory arthritis Active 75 16-25 years

Child Adt

N/K Mar-14 Newcastle University, UK








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Procedure

All age groups

"Q sort" study within a Programme of research investigating 'How can health services contribute most effectively to facilitating successful transition of young people with complex health needs from childhood to adulthood'? Observational: qualitative study UKCRN ID 12731

Service assessment

Complex health need including arthritis

Not yet Rec

40 14-23 years

Child Adt

N/K Oct-13 Royal Victoria Infirmary, UK



≤18 years

A Prospective Study of Childhood Onset Inflammatory Arthritis (Childhood Arthritis Prospective Study) UKCRN ID 2635

Childhood onset Inflammaotry arthritis

Rec 2000 <16 years

Child

N/K Dec-15 University of Manchester


All age groups

Premature cardiovascular risk associated with childhood arthritis Observational: cohort study UKCRN ID 9163

Pulse wave velocity (PWV); Carotid intima media thickness

Juvenile arthritis Active, NR

252 Adt Child

N/K Jun-11 Royal Hospital for Sick Children, Glasgow








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A4: JUVENILE-ONSET SYSTEMIC LUPUS ERYTHEMATOSUS



Start Date

End Date

Sponsors URL


≤18 years

Pediatric Lupus Trial of Belimumab Plus Background Standard Therapy Phase 2: RCT (placebo), safety/efficacy study NCT01649765

Belimumab 10mg/kg; Placebo

Systemic Lupus Erythematosus

Rec 100 5-17 years

Child

Jul-12 Mar-26 GlaxoSmithKline; Human Genome Sciences


All age groups

Phase 2 Study of Human Umbilical Cord Derived Mesenchymal Stem Cell for the Treatment of Lupus Nephritis Phase 2: RCT (active), safety/efficacy study NCT01539902

Human Umbilical Cord derived MSCs; Cyclophosphamide

Lupus Nephritis Rec 25 16-65 years

Child Adt

Feb-12 May-13 CytoMed & Beike


Age groups unknown

Comparison Between Tacrolimus (TAC) and Mycophenolate Mofetil (MMF) for Induction of Remission in Lupus Nephritis RCT (active), safety/efficacy study NCT01580865

Tacrolimus; Mycophenolate mofetil

Lupus Nephritis Not yet Rec

90 N/K May-12 Jun-15 Ramathibodi Hospital; King Chulalongkorn Memorial Hospital; Maharaj Nakorn Chiang Mai Hospital; Rajavithi Hospital; Srinagarind Hospital; Siriraj Hospital; Songklanagarind Hospital





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Safety and Tolerability of Intravenous Dose of MEDI-546 in Japanese Subjects With Systemic Lupus Erythematosus Phase 2: Single group assignment, safety study NCT01559090

MEDI-546 Systemic Lupus Erythematosus

Rec 21 N/K Apr-12 Sep-14 AstraZeneca; MedImmune LLC


WEUKBRE5716: Steroid-related Damage in Systemic Lupus Erythematosus (Hopkins) Observational: Retrospective cohort study NCT01616472

Cumulative corticosteroid exposure

Systemic Lupus Erythematosus

Active, NR

1 N/K Apr-12 Apr-14 GlaxoSmithKline http://ClinicalTrials.gov/show/NCT01616472

No intervention, observational

≤18 years

A Genetic Analysis of Systemic Lupus Erythematosus (SLE) in Children Obervational: prospective, cohort study UKCRN ID 12577

Juvenile-onset SLE Rec 100 ≤16 years

Child

N/K Apr-17 King's College London, UK


Steroid-Induced Osteoporosis in the Pediatric Population - Canadian Incidence Study Observational: Prospective cohort study NCT01663129

Acute Lymphoblastic Leukemia; Nephrotic Syndrome; Rheumatism

Active, NR

406 ≤16 years

Child

Jan-05 Jun-14 Children's Hospital of Eastern Ontario; Canadian Institutes of Health Research


Association of HLA-DR gene polymorphism and systemic lupus erythematosus (SLE) associated genes (IRF5, BLK, STAT4, TNFAIP3, TNIP1, ETS1 and SPP1 polymorphisms) with childhood-onset SLE. Observational: Retrospective cohort study UMIN000008459

SLE Active, NR

300 ≤18 years

Child

Jun-10 N/K Yokohama City University, Japan

https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&action=brows&type=summary&recptno=R000009949&language=E










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A5: NON-INFLAMMATORY MUSCULOSKELETAL DISORDERS

A5A: CHRONIC PAIN SYNDROME, COMPLEX REGIONAL PAIN SYNDROME & FIBROMYALGIA



Start Date

End Date

Sponsors URL


All age groups

Acceptance and Commitment Therapy for Adolescents and Young Adults With Neurofibromatosis and Chronic Pain Single group assignment, efficacy study NCT01633008

ACT Workshop Neurofibromatosis Rec 28 ≥12 years

Child Adt Sen

Jun-12 Jan-14 National Institutes of Health Clinical Center; National Cancer Institute



All age groups

Validating Pain Scales in Children and Young Adults NCT01639950

Solid Tumor; Leukemia; Neurofibromatosis

Rec 198 ≥6 years

Child Adt Sen

Jun-12 N/K National Institutes of Health Clinical Center; National Cancer Institute


A5B: HYPERMOBILITY, JOINT HYPERMOBILITY SYNDROME & EHLERS-DANLOS No new clinical trials identified



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A6: SCLERODERMA



Start Date

End Date

Sponsors URL


≤18 years

Campath-1h Phase I/II Pilot Trial as Immunoablative Therapy for Refractory Systemic Sclerosis Observational: Prospective cohort study NCT01639573

Scleroderma Rec 6 8-18 years

Child Adt

Apr-11 Apr-16 Children's Hospital Los Angeles


A7: VASCULITIS



Start Date

End Date

Sponsors URL


≤18 years

Infliximab (anti human-TNF-alfa monoclonal antibody, Remicade) off-label treatment for refractory Kawasaki disease Single group assignment efficacy study UMIN000007423

Infliximab Refractory Kawasaki disease

Not yet Rec

5 <18 years

Child

Mar-12 Mar-17 Saitama Medical University, Japan


Clinical Study of TA-650 in Patients With Refractory Kawasaki Disease Phase 3: RCT (active), safety/efficacy study NCT01596335

TA-650; Polyethylene Glycol-treated Human Immunoglobulin

Kawasaki Disease Refractory to Initial Therapy With Intravenous Immunoglobulin

Rec 100 1-10 years

Child

May-12 Aug-14 Mitsubishi Tanabe Pharma Corporation








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All age groups

CMV Modulation of the Immune System in ANCA-associated Vasculitis Phase 2: RCT (active), efficacy study NCT01633476

Valaciclovir ANCA Associated Vasculitis; CMV Infection

Not yet Rec

50 ≥16 years

Child Adt Sen

Aug-12 Aug-15 University of Birmingham; Professor Lorraine Harper; Wellcome Trust


Efficacy and Safety of treatment with tocilizumab in refractory patients with Takayasu Arteritis Single group assignment, safety/efficacy study UMIN000007845

Tocilizumab Takayasu arteritis Invite 15 16-60

Child Adt

May-12 Apr-14 Osaka University, Japan



All age groups

Rituximab for ANCA-associated Vasculitis (RAVE) Long-Term Follow-Up Study Observational: Prospective cohort study NCT01586858

Granulomatosis With Polyangiitis; Microscopic Polyangiitis

Invite 180 ≥12 years

Child Adt Sen

May-12 N/K Johns Hopkins University


Brainworks International Collaborative Database for Childhood CNS Vasculitis UKCRN ID 12923

CNS vasculitis or inflammatory brain disease

Not yet Rec

400 <18 years

Child

N/K Aug-15 Newcastle upon Tyne Hospitals NHS Trust


Age group unknown

Development of a Pan UK Vasculitis Cohort to Analyse Variations in Disease Susceptibility and Outcomes UKCRN ID 12689

ANCA-vasculitis including Wegener's Granulomatosis, Microscopic polyangiitis & Churg Strauss Syndrome

Rec 2000 N/K N/K Dec-14 Royal Free Hospital, UK


Identification of Biomarkers Predictive of Worse Prognosis in Henoch Schonlein Purpura Observational: Prospective cohort study NCT01610830

Purpura, Schoenlein-Henoch

Rec 120 N/K Apr-10 Dec-13 Assistance Publique - Hôpitaux de Paris













horizon scanning p upate august 2012 - keele … · feedback from a pilot horizon scanning exercise...

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