E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Juvenile Rheumatoid Arthritis |
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E.1.1.1 | Medical condition in easily understood language |
Juvenile Rheumatoid Arthritis |
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E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of this study was to evaluate the safety of anakinra |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Boys or girls age 2 to 17 years (inclusive)
• Minimum weight of 10 kg
• Availability of an adult to assist with administration of SC injections of study drug and/or subjects capable of adequately performing self-injection technique as judged by the investigator
• Available for assessments
• Polyarticular, pauciarticular or systemic disease onset
• Active polyarticular-course JRA with at least 5 swollen joints due to active arthritis (not bony overgrowth) and 3 joints with limitation of motion (LOM) at screening and the day 1 visit
• Stable doses of background methotrexate (minimum 10 mg/m2/week, maximum 40 mg/week) for 6 consecutive weeks before the first dose of anakinra and throughout the trial (subjects not receiving background methotrexate or any other DMARD for 6 weeks before the first dose of anakinra could be enrolled but not initiate methotrexate treatment while participating in this study)
• Subjects who continued methotrexate were required to take either 1 to 5 mgs/day folic acid at least 5 days/week or 2.5 to 15 mgs folinic acid the day after methotrexate administration
• Subjects had at least a 4-week washout of any other biologic therapy (eg, etanercept and infliximab) before the first dose of anakinra
• Stable doses of NSAIDS (including Cox-2 inhibitors e.g. celecoxib and rofecoxib) and systemic oral corticosteroids (≤ 10 mg/day or 0.2 mg/kg/day of prednisone; whichever was less) for 4 weeks before the first dose of anakinra and during the trial
• Subjects who received leflunomide must have completed the prescribed course of cholestyramine washout
• Provision of written informed consent for participation in the study by the subject or legally acceptable representative before any study-specific procedure was performed |
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E.4 | Principal exclusion criteria |
• Presence of any uncontrolled, clinically significant systemic disease, hepatic, renal, neurological, endocrine, cardiac, gastrointestinal (except NSAID-induced GI problems), or hematologic disease within 24 weeks of first dose of anakinra
• Presence of symptoms of systemic disease at screening (intermittent fever, rash, hepatosplenomegaly, pericarditis)
• Known diagnosis of hepatitis or HIV
• A malignancy other than basal cell or in situ carcinoma of the cervix within the previous 5 years
• Presence of any other rheumatic disease or major chronic infectious, inflammatory, immunologic disease (inflammatory bowel disease, psoriatic arthritis, spondyloarthropathy, systemic lupus erythematosus)
• Infection at screening or development of frequent, acute or chronic infection within 4 weeks
• Joint replacement required during the study
• ALT or AST > 2.0 or creatinine > 1.5 times the upper limit of normal range (confirmed by repeated measure)
• White blood cell count < 2.0 x 109/L and/or neutrophil count < 1.5 x 109/L and/or
platelet count < 150 x 109/L
• Concurrent treatment with a DMARD other than methotrexate
• Concurrent treatment of methotrexate < 10 mg/m2/week or > 40 mg/week
• Received intra-articular or systemic corticosteroid injection within 4 weeks
• Received live viral vaccines within 3 months of study
• Current enrollment in any other interventional clinical study or concurrent treatment with an investigational agent within 4 weeks of study
• Active substance abuse
• Known allergy to E coli-derived products
• Any disorder that compromised the ability to give informed consent for participation in the study, comply with protocol procedures, and/or be available for follow-up assessment
• Lack of adequate contraceptive precautions
• Pregnancy (eg, positive test for human chorionic gonadotropin), ongoing breastfeeding, or intention to become pregnant during the study |
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E.5 End points |
E.5.1 | Primary end point(s) |
Adverse events and laboratory assessment over time |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Open phase followed by double blind phase |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
Will this trial be conducted at a single site globally?
| No |
E.8.4 | Will this trial be conducted at multiple sites globally? | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.2 | Trial being conducted completely outside of the EEA | Yes |
E.8.6.3 | Specify the countries outside of the EEA in which trial sites are planned |
Australia |
Canada |
Costa Rica |
New Zealand |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.2 | In all countries concerned by the trial years | 3 |