HORIZON SCANNING: PAEDIATRIC RHEUMATOLOGY UPATE FEBRUARY 2011

Transcription

1 HORIZON SCANNING: PAEDIATRIC RHEUMATOLOGY UPATE FEBRUARY 2011 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 This follow up report includes trials registered since July 2010 for seven Topic Specific Groups (TSGs): Bone Health; Juvenile Dermatomyositis; Juvenile- Idiopathic Arthritis and JIA-associated Uveitis; Juvenile-onset Systemic Lupus Erythematosus; Noninflammatory 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 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 6 A1c: Osteogenesis imperfecta 6 A1d: Osteopetrosis 7 A1e: Osteoporosis & Osteopenia 8 A1f: (Juvenile) Paget s disease 14 A1g: Rickets & Hypophophatasia 14 A2. Juvenile Dermatomyositis. 16 A3. Juvenile Idiopathic Arthritis and JIA-associated Uveitis 17 A4. Juvenile-onset Systemic Lupus Erythematosus.. 21 A5. Non-inflammatory Musculoskeletal Disorders.. 24 A5a: Chronic pain syndrome, Complex regional pain syndrome & Fibromyalgia 24 A5b: Hypermobility, Joint hypermobility syndrome & ehlers-danlos 24 A6. Scleroderma.. 25 A7. Vasculitis Arthritis Research UK 2011

2 SEARCH METHODOLOGY Databases Searched Clinical trials databases: MetaRegister of Clinical Trials (active registers); ClinicalTrials.gov; UKCRN Portfolio Database; Australia and New Zealand Horizon Scanning Network (ANZHSN); MRC Clinical Trials Unit; Nederlands Trials Register; German Clinical Trials Register; Hospital Medical Information Network (UMIN); Japan Medical Association Center for Clinical Trials Register (JMA- CTR); Japan Pharmaceutical Information Center Clinical Trials Register. 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, glucocorticoidinduced/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; Vasculitis, Kawasaki Disease, Mucocutaneous Lymph Node Syndrome, Behcet s Syndrome, Wegener s Granulomatosis, Microscopic Polyangiitis (MPA), Microscopic Polyarteritis, Polymyalgia rheumatic, Renal limited vasculitis, Cryoglobulinaemic vasculitis, Cogan s syndrome, Takayasu s Arteritis, Churg-Strauss Syndrome, Polyarteritis Nodosa, ANCA associated vasculitis, Henoch Schonlein purpura;, ren, hood, Adolescent, Juvenile, Paediatric. limits Trials registered since July 2010 are included in the feedback. Additional search terms, notably osteopenia and vertebral/spinal fracture, are included in the Bone Health TSG scan, therefore, any corresponding clinical trials ongoing or completed since January 2009 are included in the feedback. Age limits Studies involving individuals of 18 1 of age and under were included in the report. 1 with the exclusion of studies where the lowest age limit is 18 of age. 2

3 RESULTS A total of 86 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 = 38); A2: Dermatomyositis (n = 4); A3: Juvenile idiopathic arthritis and JIA-associated uveitis (n = 15); A4: Juvenile-onset systemic lupus erythematosus (n = 12); A5: Non-inflammatory (n = 3); A6: Scleroderma (n = 2); A7: Vasculitis (n = 12). 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 (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 has a weblink which can be followed for further details. Where there was uncertainty regarding whether a 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. 3

4 ABBREVIATIONS ANCA BJHS Comp CT CT ID DM F-only Grps Invite JIA M-only mo n N/K RA RCT Rec Recruit SLE Susp Term Wtdwn Adult (18-65 ) Anti-neutrophilic Cytoplasmic Antibody Benign Joint Hypermobility Syndrome (birth-17 ) Completed Controlled trial Clinical Trials Identifier Dermatomyositis Females only Groups Invite only Juvenile Idiopathic Arthritis Males only Months Enrollement Not known Rheumatoid Arthritis Randomized controlled trial. Recruiting Recruitment ior (66+ ) Systemic Lupus Erythematosus Suspended. Terminated Withdrawn 4

5 FULL TEXT APPENDIX SECTION B: CLINICAL TRIALS Clinical trials identity number (CT ID): Prefix of NCT denotes National Clinical Trials Identifier; ISRCTN - International Standard Randomized Controlled Trial Number; UKCRN UK Clinical Research Network; ACTRN Australian New Zealand Clinical Trials Registry; NTR Nederland Trial Register; DRK German clinical Trials Register; UMIN Hospital Medical Information Network; JMA - Japan Medical Association Center for Clinical Trials Register; JapicCTI - Japan Pharmaceutical Information Center Clinical Trials Identifier. 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 Title Phases: trial design (control) CT ID No intervention: observational Prognosis Association of Calcium Hypocalcemia on Moderate-severe Measurement TBI, COHORTE STUDY Observational: Prospective, cohort NCT Interventions Conditions Recruit n Age (Grp) Hypocalcemia Rec Start End Sponsors Oct-10 Nov-12 Universidad Autonoma de San Luis Potosí URL 5

6 A1B: DYSPLASIA & MCCUNE-ALBRIGHT SYNDROME Title Phases: trial design (control) CT ID Other interventions including CAM Distraction osteogenesis with Culture expanded transplantation of culture bone marrow cells; expanded bone marrow cells no cell therapy Phase II/III: Non-randomized, parallel assignment, safety/efficacy UMIN Interventions Conditions Recruit n Age (Grp) Skeletal dysplasia; Limb length discrepancy Comp 50 < 20 Start End Sponsors Aug-02 Dec-09 Nagoya Hospital URL s&type=summary&recptno=r &l an No intervention, observational 18 Risk factors in hip dysplasia UKCRN ID 9571 Developmental dysplasia of the hip Active weeks N/K Mar-13 College London Hospital il.aspx?studyid=9571 A1C: OSTEOGENESIS IMPERFECTA No new clinical trials identified 6

7 A1D: OSTEOPETROSIS Title Phases: trial design (control) CT ID Procedure Expanded Access Protocol (EAP) Using the CliniMACS Device for Pediatric Haplocompatible Donor Stem Cell Transplant NCT Interventions Conditions Recruit n Age (Grp) CD34+ enriched, T Cell Depleted donor stem cell product Acute Lymphoblastic Leukemia; Acute Myeloid Leukemia; Chronic Myeloid Leukemia; Myelodysplastic Syndrome; Lymphomas; Bone Marrow Failure; Hemoglobinopathy; Immune Deficiency; Osteopetrosis; Cytopenias; White Blood Cell Abnormalities; Red Blood Cell Abnormalities Active N/K 0-21 ; Adult Start End Sponsors Sep-10 Sep-20 of California, San Francisco URL No intervention, observational Clinical Assessment of Patients With High Bone Mass Due to Mutation in Lrp5 Observational: Cross-sectional, case-control NCT Osteopetrosis Comp 38 Jan-09 Jun-10 Odense Hospital 7

8 A1E: OSTEOPOROSIS & OSTEOPENIA Title Phases: trial design (control) CT ID Behavioural, education & exercise including physiotherapy 18 Influence of External Factors on Daily School physical Fractures Skeletal Growth in Youth education Single group assignment NCT The Effect of Physical Activity on Bone Mineralization and Immune System in Very Low Birth Weight Infants Randomized, parallel assignment, efficacy NCT Effect of High-Calcium Milk and Weight-Bearing Exercise on Bone Mineral Status of Pre-Pubertal Girls Randomized, factorial assignment, efficacy NCT Interventions Conditions Recruit n Age (Grp) Passive physical activity Osteopenia Of Prematurity Active, not Rec Not yet Rec Exercise and milk Osteoporosis Active, not Rec <14 days F- only Start End Sponsors Aug-99 Dec-15 Region Skane Jan-10 Sep-11 Meir Medical Center Feb-09 Dec-10 Nutrition Center of the Philippines; Nestle foundation URL Device Improving Low Bone Mass With Vibration Therapy in Adolescent Idiopathic Scoliosis (AIS) Phase III Randomized, parallel assignment, efficacy NCT Vibration Platform Scoliosis; Bone Diseases, Metabolic Active, not Rec F- only Jan-09 Dec-11 Chinese of Hong Kong 8

9 Dietary supplements 18 Calcium + Vitamin D Supplementation for Low Bone Mass in Adolescent Idiopathic Scoliosis (AIS) Phase III: RCT (placebo), efficacy NCT Calcium Metabolism in Mexican American Adolescents RCT (crossover), dose comparison NCT Calcium 600mg plus Vit D 400 IU; Calcium 600mg plus Vit D 800 IU; Placebo Low Calcium Diet; High Calcium Diet Scoliosis Rec F- only Osteoporosis Comp Apr-10 Apr-13 Chinese of Hong Kong Apr-10 Aug-10 Purdue ; Eunice Kennedy Shriver National Institute of Health and Human Development The bone metabolism of low BMD young women and its management Phase IV: Single group assignment, efficacy UMIN Vitamin K Osteopenia Active F- only May-09 Apr-11 Kobe s&type=summary&recptno=r &l an Drug including biologics 18 Trial of Dextromethorphan in Rett Syndrome Phase II: Randomized, parallel assignment, dose comparison, efficacy NCT Dextromethorphan; Delsym Rett Syndrome Rec Aug-04 Nov-12 FDA Office of Orphan Products Development; Eunice Kennedy Shriver National Institute of Health and Human Development; National Center for Research Resources

10 The efficacy and safety of zoledronate in children and adolescents with chronic neurological conditions and osteoporosis: a crossover trial with long term follow up. Non-randomized, crossover, safety/efficacy ACTRN Clinical trial of zoledronic acid in children and adolescents with Duchenne muscular dystrophy RCT (active), efficacy ACTRN Zoledronate Osteoporosis active Zoledronic acid (Aclasta) Duchenne muscular dystrophy; bone density; osteopenia Active M- only Apr-10 > Oct-12 Princess Margaret Hospital for ren Sep-10 > Royal ren's Sep-11 Hospital, Parkville; The ren's Hospital at Westmead = = Fat Mediated Modulation of Reproductive and Endocrine Function in Young Athletes Phase III: Randomized, parallel assignment, efficacy NCT Year Open-label Extension to CZOL446H2337 Safety and Efficacy Trial of Zoledronic Acid Twice Yearly in Osteoporotic ren Treated With Glucocorticoids for Chronic Inflammatory Conditions Phase III: Single group assignment NCT Transdermal 17Betaestradiol, Female Athlete Triad Amenorrhea; progesterone; Ethinyl Syndrome Estradiol + Desogestrel; Elemental Calcium and Vitamin D Rec F- only Zoledronic acid Osteoporosis Rec May-09 Nov-14 Massachusetts General Hospital; Eunice Kennedy Shriver National Institute of Health and Human Development (NICHD) Oct-10 Jul-11 Novartis Pharmaceuticals 10

11 A randomized open-label blinded prospective designed to compare the efficacy and safety between once-weekly and daily administration of alendronate in patients with corticosteroidinduced osteoporosis RCT (active), safety/efficacy UMIN Effects of rhigf-1 on Bone Metabolism in Adolescent Girls With Anorexia Nervosa Phase II: Single group assignment, safety/efficacy NCT Prevention of Post Operative Bone Loss in ren RCT (placebo), efficacy NCT Effect of Growth Hormone on Bone Metabolism in Anorexia Nervosa Phase II: RCT (placebo), efficacy NCT Rec 130 >16 rhigf-1 Bone Density Rec Pamidronate; saline Osteoporosis; Cerebral Palsy; Spina Bifida; Osteopenia; Osteogenesis Imperfecta Recombinant Human Anorexia Nervosa; Growth Hormone; Osteopenia; Placebo for Osteoporosis; Eating Recombinant Human Disorders Growth Hormone F- only Rec Comp F- only Mar-08 Jun-11 Keio Aldendronate onceweekly; aldendronate induced Corticosteroid- daily administration. osteoporosis s&type=summary&recptno=r &l an Jul-08 Dec-10 Massachusetts General Hospital Sep-07 Feb-10 of New Mexico; Thrasher Research Fund Jan-06 Feb-09 Massachusetts General Hospital; Genentech

12 Procedures Development of minimally invasive Vertebroplasty: treatments for Osteoporotic vertebra fractures Non-randomized, parallel assignment, safety/efficacy UMIN Research of safety and efficacy of percutaneous vertebroplasty for fragile bone lesions due to metastatic bone tumor or osteoporosis Phase I/II: single group assignment, safety/efficacy UMIN Percutaneous vertebroplasty Osteoporotic vertebra fractures Osteoporosis; Metastatic bone tumour Active 100 Invite 6 80 Jun-09 Mar-12 Tokyo Medical and Dental Calcium phosphate cement (CPC) + General anesthesia (GA); Vertebroplasty: CPC by uromatic balloon + GA; Percutaneous Vertebroplasty: CPC + local anesthesia; Vertebroplasty: Hydroxyapatite + GA; Percutaneous Vertebroplasty: polymethylmethacrylate + GA s&type=summary&recptno=r &l an Jan-10 > Jan-10 Saga s&type=summary&recptno=r &l an No intervention: observational 18 Bone size, body size, and fracture in childhood UKCRN ID 6165 Fracture Comp 630 N/K? N/K Mar-10 of Bristol il.aspx?studyid=

13 Proton Pump Inhibitor Therapy and Bone Density in Premature Infants Observational: Case-control NCT Osteopenia; Prematurity Rec Apr-09 Apr-11 of week Utah gestat ion g birth weigh t Clinical Assessment of Patients With High Bone Mass Due to Mutation in Lrp5 Observational: Cross-sectional, case-control NCT Develop and Validate Ultrasonic Device for Osteoporotic Fracture Risk Assessment Observational: Retrospective, Case-control NCT Frequency of Female Athlete Triad Among Elite Female Athlete of Iran in Different Sport in 2007 Observational: Cross-sectional NCT Osteopetrosis Comp 38 8 Osteoporosis; Fracture; Aging Menstruation Disturbances; Eating Disorder; Bone Loss Invite 150 F- only Term F- only Jan-09 Jun-10 Odense Hospital May-10 May-11 Artann Labs; National Institutes of Health; National Institute on Aging; Mayo Clinic Oct-06 Mar-09 Tehran of Medical Sciences Age group unknown Osteoporosis Research Registry Observational: Prospective NCT The Framingham Study: Examining DNA Markers and Links to Diseases NCT Osteoporosis Invite 200 N/K Nov-08 Dec-15 Northwestern ; Rehabilitation Institute of Chicago Vascular Diseases Comp 330 N/K Jun-03? National Heart, May-10 Lung, and Blood Institute (NHLBI) 13

14 A1F: (JUVENILE) PAGET S DISEASE No new clinical trials identified A1G: RICKETS & HYPOPHOPHATASIA Title Phases: trial design (control) CT ID Dietary Supplement 18 Study Comparing Two Isoforms of Vitamin D Supplements for Infants Phase III: Randomized, parallel assignment, bio-equivalence NCT Vitamin D Supplementation in Breastfeeding Women Phase II/III: Randomized, parallel assignment, safety/efficacy NCT Interventions Conditions Recruit n Age (Grp) Cholecalciferol (D3) or ergocalciferol (D2) Healthy Rec 48 < 6 week Vitamin D3; Vitamin D3 Vitamin D Deficiency; Rickets; Infant; Nutrition Rec 80 1 mo 50 Start End Sponsors Mar-10 Aug-11 McGill ; Canadian Foundation for Dietetic Research (Canada) Dec-10 May-11 Mayo Clinic URL Intermittent maternal cholecalciferol Oral supplementation to prevent vitamin D cholecalciferol; deficiency in the breast feeding infant placebo and lactating mother. RCT (placebo), efficacy ACTRN Vitamin D Deficiency Active mo Apr-11 > Dunedin School Aug-11 of Medicine; Dunedin Public Hospital =

15 Drug including biologics 18 Open-Label Study of ENB-0040 in Infants and ren < 5 Years of Age With Hypophosphatasia (HPP) Phase II/III: Single group assignment, safety/efficacy NCT Therapeutic Use of Oral Sodium Phosphate (Z-521) in Primary Hypophosphatemic Rickets Phase III: Single group assignment, safety/efficacy NCT Extension Study of Protocol ENB ENB-0040 Treatment in Severly Affected Infants and Young ren With Hypophosphatasia (HPP) Phase I/II: Single group assignment, safety/efficacy NCT Extension Study of Protocol ENB ENB-0040 Treatment in ren With Hypophosphatasia Phase II: Non-randomized, crossover assignment, safety/efficacy NCT ENB-0040 Hypophosphatasia Rec 30 < 5 Z-521 Primary Hypophosphatemic Rickets ENB-0040 Hypophosphatasia Active, not Rec ENB-0040 Hypophosphatasia Active, not Rec Rec mo Jul-10 Dec-13 Enobia Pharma Sep-10 Mar-13 Zeria Pharmaceutical Apr-09 May-12 Enobia Pharma Apr-10 Jul-11 Enobia Pharma No intervention: observational 18 Allogeneic Bone Marrow and Mesenchymal Stem Cell Transplantation for patients with severe Hypophosphatasia Phase II/III: Single group assignment, efficacy UMIN Allogeneic Bone Marrow and Mesenchymal Stem Cell Transplantation Hypophosphatasia Active 5 < 6 mo Jul-10 > Jul-10 Shimane School of Medicine s&type=summary&recptno=r &la n 15

16 A2: JUVENILE DERMATOMYOSITIS Title Phases: trial design (control) CT ID Dietary supplements Creatine Supplementation in Pediatric Rheumatology RCT (placebo), safety/efficacy NCT Interventions Conditions Recruit n Age (Grp) Creatine; placebo (dextrose) Juvenile Systemic Lupus Erythematosus; Juvenile Dermatomyositis Not yet Rec Start End Sponsors URL Jan-11 Jan-12 of Sao Paulo Drugs including biologics Continuous intravenous infusion Cyclosporine therapy with cyclosporine A for A rapidly progressive interstitial pneumonia associated with dermatomyositis and Polymyositis Single group assignment, safety/efficacy UMIN Investigation in Myositisassociated Pneumonitis of Prednisolone And Concomitant Tacrolimus JMA-IIA00012 Tacrolimus + corticosteroid; corticosteroid Dermatomyositis; Polymyositis Polymyositis; Dermatomyositis; interstitial pneumonitis Active 10 >16 N/K Apr-09 Apr-12 Shinshu School of Medicine Jul-07 Feb-10 IMPPACT central office s&type=summary&recptno=r &l an pp/jmactrs06/jmactrs06.aspx?seqno =322 Age not known Prospective of pulmonary infections in patients with rheumatic diseases undergoing immunosuppressive therapy Observational: prospective cohort, safety UMIN Immunesuppressive treatments RA (including RA with vasculitis), SLE; Polymyositis; Dermatomyositis; systemic sclerosis; mixed connective tissue disease; vasculitis syndrome; primary Sjogren's syndrome; Bechet disease; adult onset Still's disease Active 1000 N/K Jun-08 Mar-12 Tokyo Medical and Dental s&type=summary&recptno=r &l Graduate School an 16

17 A3: JUVENILE IDIOPATHIC ARTHRITIS AND JIA-ASSOCIATED UVEITIS Title Phases: trial design (control) CT ID Interventions Conditions Recruit n Age (Grp) Behavioural, education & exercise including physiotherapy 18 Jointstrong Intervention for Juvenile Arthritis RCT (active), efficacy NCT CD-ROM; Waitlist Control Group JIA Rec Start End Sponsors Apr-09 Mar-11 of Kansas URL Dietary supplements Effects of a combination treatment using probiotics and methotrexate (MTX) in patients with rheumatoid arthritis RCT (active), efficacy UMIN Methotrexate + probiotic; Methotrexate RA Not yet Rec 40 >16 Aug-10 Mar-15 Yokohama City Medical Center &type=summary&recptno=r &lan Drug including biologics 18 A Study of the Safety and Efficacy of CNTO 148 CNTO 148 (Golimumab) in ren (Golimumab); With Juvenile Idiopathic Arthritis (JIA) placebo and Multiple Joint Involvement Who Have Poor Response to Methotrexate (GO KIDS) Phase III: Randomized, parallel assignment, safety/efficacy NCT A Study of the Efficacy and Safety of Adalimumab in Pediatric Subjects With Enthesitis Related Arthritis Phase III: Randomized, parallel assignment, safety/efficacy NCT Adalimumab; Placebo Juvenile Idiopathic Arthritis Enthesitis; Ankylosing Spondylitis; Sacroiliitis; Inflammatory Back Pain; Juvenile Rheumatoid Arthritis Rec Rec Dec-10 Apr-16 Centocor, Inc.; Schering-Plough (Ireland) Company Sep-10 Jun-14 Abbott 17

18 Withdrawal of Etanercept After Successful Treatment of Juvenile Idiopathic Arthritis Phase IV: Randomized, parallel assignment, safety/efficacy NCT Efficacy and Safety Dose Finding Study of Givinostat to Treat Polyarticular Course Juvenile Idiopathic Arthritis Phase II: Non-randomized, parallel assignment, dose comparison, safety/efficacy NCT The influence of polymorphism in methotrexate pathway genes on efficacy and toxicity of methotrexate in patients with juvenile idiopathic arthritis Observational: safety/toxicity. UMIN Etanercept Givinostat Juvenile Idiopathic Arthritis Polyarticular Course Juvenile Idiopathic Arthritis Rec Rec Methotrexate Articular-type JIA Comp 100 <18 Jan-11 Sep-13 Erasmus Medical Center; Dutch Arthritis Association Oct-10 Aug-11 Italfarmaco May-07 May-09 Yokohama City School of Medicine &type=summary&recptno=r &lan The efficacy evaluation of tocilizumab Tocilizumab to glucocorticoid-resistant patients with adult Still's disease and systemic juvenile idiopathic arthritis: the open trial Single group assignment, efficacy UMIN Study on the glucocorticoid-sparing Tocilizumab effects of tocilizumab among glucocorticoid-dependent patients with adult Still's disease and systemic juvenile idiopathic arthritis: the open trial Single group assignment, efficacy UMIN Active 10 >16? Active 10 >16? Oct-08 Mar-13 Jichi Medical Jul-08 Mar-13 Jichi Medical Adult Still's disease; systemic JIA; steroidresistant &type=summary&recptno=r &lan Adult Still's disease; systemic JIA; glucocorticoiddependent &type=summary&recptno=r &lan 18

19 Comparison of the clinical responses by the dosage of once or triple a week of MTX in patients with rheumatoid Arthritis RCT (active), efficacy UMIN Study for Predictors of Effectiveness in Tocilizumab Therapy (PETITE) Observational: Phase IV, efficacy UMIN Corticosteroid-sparing effect of Tocilizumab Actemra in patients with Rheumatoid (actemra) Arthritis refractory to anti-tnf agents, methotrexate and corticosteroid Single group assignment, efficacy UMIN Methotrexate RA Active Tocilizumab RA Active RA Active Jun-09 Sep-11 Oribe Rheumatism Clinic Jul-09 Aug-11 Osaka City Medical School Nov-10 > Tenri Hospital Nov-10 &type=summary&recptno=r &lan &type=summary&recptno=r &lan &type=summary&recptno=r &lan All group unknown Survival analysis of prospective and retrospective systematic cohort in newly diagnosed rheumatoid arthritis patients UMIN RA Active 900 N/K Jul-07 Jul-17 Keio &type=summary&recptno=r &lan Clinical to investigate the optimal management of rheumatoid Biologics RA Active 1500 N/K Feb-09 Mar-13 Tokyo Women's Medical arthritis from the mortality perspective Observational: prospective safety/efficacy UMIN Prospective of pulmonary Immunesuppressive infections in patients with rheumatic diseases undergoing treatments immunosuppressive therapy Observational: prospective cohort, safety UMIN RA, SLE; Polymyositis; Dermatomyositis; systemic sclerosis; mixed connective tissue disease; vasculitis syndrome; primary Sjogren's syndrome; Bechet disease; adult onset Still's disease Active 1000 &type=summary&recptno=r &lan N/K Jun-08 Mar-12 Tokyo Medical and Dental &type=summary&recptno=r &lan Graduate School 19

20 No intervention: observational 18 Association of HLA-DR gene polymorphism and rheumatoid arthritis associated genes (PADI4 and IRF5 polymorphisms) with juvenile idiopathic arthritis. Observational: case-control UMIN JIA Active 200 <18 Dec-09 Jun10 Yokohama City School of Medicine &type=summary&recptno=r &lan Evidence of premature risk of cardiovascular disease associated with juvenile idiopathic arthritis? UKCRN ID 9163 JIA Active 252 N/K Jan10 NHS Greater Glasgow & Clyde l.aspx?studyid=9163 Age groups unknown Scottish Early Rheumatoid Arthritis inception cohort and biobank (SERA) UKCRN ID 9162 The role of Magnetic Resonance Imaging (MRI), Ultrasound (US) and novel serum markers in predicting disease flare in Juvenile Idiopathic Arthritis (JIA) UKCRN ID 9166 Early RA Active 5400 N/K N/K Nov-13 NHS Greater Glasgow & Clyde JIA Active 60 N/K N/K Nov-10 NHS Greater Glasgow & Clyde l.aspx?studyid= l.aspx?studyid=

21 A4: JUVENILE-ONSET SYSTEMIC LUPUS ERYTHEMATOSUS Title Phases: trial design (control) CT ID Dietary supplement Creatine Supplementation in Pediatric Rheumatology RCT (placebo), safety/efficacy NCT Drug including biologics 18 Mizolibin for systemic lupus erythematosus in children (JSRDC10) Single group assignment, safety/efficacy C Interventions Conditions Recruit n Age (Grp) creatine; placebo (dextrose) Juvenile Systemic Lupus Erythematosus; Juvenile Dermatomyositis Not yet Rec Mizolibin SLE Active Start End Sponsors URL Jan-11 Jan-12 of Sao Paulo Mar-06 Aug-10 Japanese Study Group of Renal Disease in ren (JSRDC) &type=summary&recptno=r &lan The Efficancy and Tolerance of Tacrolimus Sustained-release Capsules in Induction Treatment in Lupus Nephritis Phase III: Single group assignment, safety/efficacy NCT A Randomized, Double-blind, Placebo-controlled, Multicenter, Phase II/III of Rituximab in Patients with Systemic Lupus Erythematosus RCT (placebo), safety/efficacy UMIN Tacrolimus Sustained-release Capsules (ADVAGRAF) Rituximab + oral prednisolone; placebo + oral prednisolone Lupus Nephritis Rec SLE Comp Jan-11 Dec-12 Sun Yat-sen Mar-07 Mar-11 Zenyaku Kogyo Co., Ltd. &type=summary&recptno=r &lan 21

22 Phase II of Rituximab in Patients with Systemic Lupus Erythematosus Phase II: Single group assignment, safety/efficacy UMIN Phase II of rituximab in patients with severe systemic lupus erythematosus Phase II: Single group assignment, efficacy UMIN Tacrolimus Versus Cyclophosphamide as Treatment for Severe Lupus Nephritis Phase I: Non-randomized (active), safety/efficacy NCT Rituximab SLE Active 70 <80 Rituximab SLE Comp Tacrolimus; cyclophosphamide SLE; Lupus Nephritis; Renal Insufficiency; End-Stage Renal Disease Comp May-07 Mar-12 Zenyaku Kogyo Co., Ltd. May-07 Jul-10 Zenyaku Kogyo Co., Ltd. Mar-03 Jun-10 Zhejiang &type=summary&recptno=r &lan &type=summary&recptno=r &lan Age group unknown Prospective of pulmonary Immune-suppressive RA (including RA infections in patients with rheumatic diseases undergoing immunosuppressive therapy Observational: prospective cohort, safety UMIN treatments with vasculitis), SLE; Polymyositis; DM; systemic sclerosis; mixed connective tissue disease; vasculitis syndrome; primary Sjogren's syndrome; Bechet disease; adult onset Still's disease Active 1000 N/K Jun-08 Mar-12 Tokyo Medical and Dental &type=summary&recptno=r &lan Graduate School 22

23 Other interventions including CAM The effects of adjuvant Tualang honey therapy on disease activity markers in systemic lupus erythematosus patients RCT (active), efficacy ACTRN Oral Tualang honey; standard maintenance treatment low dose steroid with or without immunosuppressive drugs (cyclophosphomide, azathioprine) SLE Comp Oct-09 > Universiti Sains Apr-10 Malaysia = No intervention, observational The role of TRIM family in rheumatic diseases and aquired immunodeficiency syndrome UMIN SLE; Behcet disease; Sjogren's syndrome; HIV infection; Healthy control Active 300 >16 Aug-10 > Aug-10 Yokohama City &type=summary&recptno=r &lan Age groups unknown Role of sctla-4 in regulating immune response in lupus UKCRN CT 9395 MRI of steroid-induced osteonecrosis UMIN SLE Active 266 N/K N/K May-13 of Aberdeen SLE and steroidinduced osteonecrosis l.aspx?studyid=9395 Comp 120 N/K Aug-08 Aug-09 Chiba &type=summary&recptno=r &lan 23

24 A5: NON-INFLAMMATORY MUSCULOSKELETAL DISORDERS A5A: CHRONIC PAIN SYNDROME, COMPLEX REGIONAL PAIN SYNDROME & FIBROMYALGIA Title Phases: trial design (control) CT ID Drug including biologics 18 A Study of Duloxetine in Adolescents With Juvenile Primary Fibromyalgia Syndrome Phase III: RCT (placebo), safety/efficacy NCT Interventions Conditions Recruit n Age (Grp) Duloxetine; Placebo Fibromyalgia Not yet Rec Start End Sponsors 210 Feb-11 Apr-15 Eli Lilly and Company URL No intervention, observational Age group unknown Epidemiology of Fibromyalgia in Japan Observational: cross-sectional UMIN Fibromyalgia Active N/K Apr-10 > Tokyo-Eki Apr-10 Center-building Clinic s&type=summary&recptno=r &l an A5B: HYPERMOBILITY, JOINT HYPERMOBILITY SYNDROME & EHLERS-DANLOS Title Phases: trial design (control) CT ID Other intervention 18 Multidisciplinary intervention for treatment of BJHS in childhood Efficacy UKCRN 9366 Interventions Conditions Recruit n Age (Grp) Multidisciplinary intervention Benign Joint Hypermobility Syndrome Active Start N/K End Sponsors Jan-12 Norfolk and Norwich Hospital NHS Trust URL il.aspx?studyid=

25 A6: SCLERODERMA Title Phases: trial design (control) CT ID Other intervention Manual lymph drainage in systemic sclerosis RCT ISRCTN Interventions Conditions Recruit n Age (Grp) Manual lymph drainage; normal treatment Systemic sclerosis with oedematous hands Comp 32 Start End Sponsors Mar-09 Mar-10 of Florence (Italy) URL No intervention, observational Age group unknown Investigation of skin autofluorescence in systemic sclerosis Observational: cross-sectional UKCRN ID 9431 Systemic sclerosis Active 60 N/K N/K Dec-12 Hope Hospital, Manchester (UK) ail.aspx?studyid=

26 A7: VASCULITIS Title Phases: trial design (control) CT ID Drug including biologics 18 Randomized controlled trial to Assess Immunoglobulin plus Steroid Efficacy for Kawasaki disease Phase III: RCT (active), efficacy UMIN Interventions Conditions Recruit n Age (Grp) Intravenous immunoglobulin + aspirin; Intravenous immunoglobulin + aspirin + Intravenous Prednisolone + Famotidine Kawasaki disease Active 392 N/K Refractory Kawasaki Disease? Comp 20 N/K? Start End Sponsors URL Sep-08 Apr-11 Tohru Kobayashi &type=summary&recptno=r &lan Apr-07 Feb-11 Kitasato Clinical trial of Methyl-prednisolone Pulse methylprednisolone pulse conbined therapy for Refractory Kawasaki Disease: Trial in Single Institution UMIN &type=summary&recptno=r &lan A Study of Adalimumab in Japanese Subjects With Intestinal Behçet's Disease Phase III: Single group assignment, efficacy NCT Prospective of the severitybased treatment protocol for Japanese patients with MPO- ANCA-associated vasculitis Single group assignment, safety/efficacy UMIN Adalimumab Intestinal Behçet's Disease Severe cases: IV MPO-ANCA CY or oral CY + positive; prednisolone. microscopic Most severe: add polyangiitis; plasma exchange. polyarteritis nodosa; Omit cyclophosphamide for glomerulonephritis rapidly progressive aged cases with RPGN and dialysed cases. Mild cases: Prednisolone alone or with azathioprine. Rec Active 50 <80 Oct-10 Dec-12 Abbott; Eisai Co., Ltd. Sep-04 Mar-11 Ministry of Health, Labor and Welfare of Japan &type=summary&recptno=r &lan 26

27 Pilot to assess efficacy and Cyclosporine safety of Cyclosporine for refractory Kawasaki disease Single group assignment, safety/efficacy UMIN Tocilizumab treatment of cyclophosphamide-resistant patients with ANCA-associated vasculitis Single group assignment, safety/efficacy UMIN Tocilizumab Refractory Kawasaki disease ANCA-associated vasculitis RA (including RA with vasculitis), SLE; Polymyositis; Dermatomyositis; systemic sclerosis; mixed connective tissue disease; vasculitis syndrome; primary Sjogren's syndrome; Bechet disease; adult onset Still's disease ANCA-associated vasculitis Comp 30 >4 mo, <20 Active, NR May-08 Jan-11 Chiba &type=summary&recptno=r &lan 15 N/K Apr-06 Mar-14 Ministry of Health, Labor and Welfare of Japan &type=summary&recptno=r &lan Age groups unknown Rituximab treatment of Rituximab cyclophosphamide-resistant patients with ANCA-associated vasculitis Single group assignment, safety/efficacy UMIN Prospective of pulmonary Immunesuppressive infections in patients with rheumatic diseases undergoing treatments immunosuppressive therapy Observational: prospective cohort, safety UMIN Active 1000 N/K Jun-08 Mar-12 Tokyo Medical and Dental &type=summary&recptno=r &lan Graduate School Active 5 N/K Mar-11 > Ministry of Mar-11 Health, Labor and Welfare of Japan &type=summary&recptno=r &lan 27

28 No intervention, observational One-Time DNA Study for Vasculitis Observational: Prospective, cohort NCT Clinical Relevance of Anti- Neutrophil Cytoplasm Antibody (ANCA) in Hospitalized Patients Observational: retrospective, cohort NCT The Characterisation and Determinants of Quality of Life in ANCA Associated Vasculitis UKCRN ID 9158 The role of TRIM family in rheumatic diseases and aquired immunodeficiency syndrome UMIN Interpretation of blood test results Giant Cell Arteritis; Takayasu's Arteritis; Polyarteritis Nodosa; Wegener's Granulomatosis; Microscopic Polyangiitis; Churg- Strauss Syndrome ANCA-related Vasculitis ANCA sssociated basculitis cohort: Wegener s granulomatosis; microscopic polyangiitis; Churg- Strauss syndrome, Disease cohort: inflammatory arthritis or chronic renal insufficiency. General population Behcet disease; Sjogren's syndrome; HIV infection; Healthy control Rec Not yet Rec Active N/K 300 >16 Oct-10 Aug-14 Boston ; National Institute of Arthritis and Musculoskeletal and Skin Diseases; Office of Rare Diseases; Rare Diseases Clinical Research Network Dec-10 Dec-11 Hillel Yaffe Medical Center N/K Sep-11 of Aberdeen Aug-10 > Yokohama City Aug-10 Graduate School of Medicine l.aspx?studyid=9158 &type=summary&recptno=r &lan 28