E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Polyarticular Juvenile Rheumatoid Arthritis |
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E.1.1.2 | Therapeutic area | Diseases [C] - Musculoskeletal Diseases [C05] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10036039 |
E.1.2 | Term | Polyarticular juvenile rheumatoid arthritis, chronic or unspecified |
E.1.2 | System Organ Class | 10028395 - Musculoskeletal and connective tissue disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Efficacy - to determine and compare disease flare in non-MTX/adalimumab treated subjects to non-MTX/placebo treated subjects who had previously responded to adalimumab treatment.
Safety - to contrast the safety profile of adalimumab with placebo in non-MTX treated subjects; to contrast the safety profile of adalimumab with placebo in concomitant MTX-treated subjects; to evaluate the long term safety profile of repeated subcutaneous adminstration of adalimumab in pediatric subjects with polyarticular JRA.
Pharmacokinetics - to estimate adalimumab population pharmacokinetic parameters in pediatric subjects (at least 4 years old) with polyarticular JRA. |
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E.2.2 | Secondary objectives of the trial |
Efficacy - to determine and compare time to onset of flare and in disease flare in non-MTX/adalimumab treated subjects to non-MTX/placebo treated subjects; to determine continued clinical benefit at the 30%, 50% and 70% improvement response after repeated subcutaneous administration of adalimumab; to compare the safety and efficacy of fixed eow dosing based on body weight to variable eow dosing based on BSA of subjects rolled over into the Fixed Dose Open Label portion of the trial.
Pharmacokinetics - to characterise adalimumab pk and identify important subject characteristics that will explain pk variability in pediatric subjects with polyarticular JRA; to compare adalimumab pharmacokinetics in children with JRA to adult JRA subjects; to compare the PK of fixed eow dosing based on body weight to variable eow dosing based on BSA of subjects rolled over into the Fixed Dose Open Label portion of the trial whose PK samples will be drawn. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
•Subjects must have a diagnosis of polyarticular juvenile rheumatoid arthritis (JRA) age 4 to 17 by the American College of Rheumatology (ACR) criteria. Disease onset may have been systemic, polyarticular, or pauciarticular. If the disease was systemic onset, then the subjects must be free of any systemic JRA manifestations for at least 3 months before the time of qualification.
•At the time of study screening, the subject must have continuing active disease defined as >= 5 swollen joints and >= 3 joints with limitation of motion (LOM). These joints are not mutually exclusive.
•Subjects may be either naïve to MTX, inadequate responders to MTX, or intolerant to MTX. Intolerance to MTX will be defined by the subject's physician. The MTX must be maintained at a dose of at least 10 mg/m2 body surface area/week for a minimum of 3 months, prior to screening.
•Duration of disease is not limited, but must have been long enough for a subject to have been given an adequate trial of nonsteroidal anti-inflammatory drugs (NSAIDs).
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E.4 | Principal exclusion criteria |
•Pregnant or nursing female.
•Functional class IV by ACR criteria.
•Laboratory parameters outside limits established in the protocol.
•Medical history, medical condition, or previous treatment not allowed by the protocol.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint was the number of adalimumab-treated subjects in the non-MTX stratum with disease flare during the Double-Blind Phase compared with the number of placebo-treated subjects in the non-MTX stratum with disease flare during the double-blind phase. Subjects met the criteria for disease flare if they had 1) >= 30% worsening in at least 3 of the 6 Juvenile Rheumatoid Arthritis (JRA) core set criteria and a minimum of 2 active joints, and 2) >= 30% improvement in not more than 1 of the 6 JRA core set criteria. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Time Frame: Week 16 to Week 48 (32 weeks) |
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E.5.2 | Secondary end point(s) |
•Number of Subjects Meeting Pediatric American College of Rheumatology 30% (PedACR30) Response Criteria at the End of the Open-Label Lead-In Phase
•Number of Subjects in the MTX Stratum With Disease Flare During the Double-Blind Phase
•Time to Onset of Disease Flare During the Double-Blind Phase in Subjects in the Non-MTX Stratum
•Time to Onset of Disease Flare During the Double-Blind Phase in Subjects in the MTX Stratum
•Number of Subjects Meeting PedACR30 Response Criteria at the End of the Double-Blind Phase
•Number of Subjects Meeting PedACR50 Response Criteria at the End of the Double-Blind Phase
•Number of Subjects Meeting PedACR70 Response Criteria at the End of the Double-Blind Phase
•Mean Change From Baseline in Physician's Global Assessment of Disease Activity at Week 48 of the Double-Blind Phase
•Mean Change From Baseline in Parent's/Patient's Global Assessment of Disease Activity at Week 48 of the Double-Blind Phase
•Mean Change From Baseline in C-Reactive Protein Levels at Week 48 of the Double-Blind Phase
•Number of Subjects Meeting PedACR30/50/70 Response Criteria at Baseline of the Open-Label Extension Body Surface Area Phase
•Number of Subjects Meeting PedACR30/50/70 Response Criteria at Week 56 of the Open-Label Extension Body Surface Area Phase
•Number of Subjects Meeting PedACR30/50/70 Response Criteria at Week 104 of the Open-Label Extension Body Surface Area Phase
•Number of Subjects Meeting PedACR30/50/70 Response Criteria at Baseline of the Open-Label Extension Fixed Dose Phase [ Time Frame: Baseline ]
•Number of Subjects Meeting PedACR30/50/70 Response Criteria at Week 48 of the Open-Label Extension Fixed Dose Phase
•Number of Subjects Meeting PedACR30/50/70 Response Criteria at Week 112 of the Open-Label Extension Fixed Dose Phase
•Number of Subjects Meeting PedACR30/50/70 Response Criteria at the Final Visit (up to 224 Weeks) of the Open-Label Extension Fixed Dose Phase |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
[ Time Frame: Week 16 ]
[ Time Frame: Week 16 to Week 48 (32 Weeks) ]
[ Time Frame: Week 16 to Week 48 (32 weeks) ]
[ Time Frame: Week 16 to Week 48 (32 weeks)
[ Time Frame: Week 48 ]
[ Time Frame: Week 48 ]
[ Time Frame: Week 48 ]
[ Time Frame: Baseline and Week 48 ]
[ Time Frame: Baseline and Week 48 ]
[ Time Frame: Baseline and Week 48 ]
[ Time Frame: Open-Label Lead-In Phase Baseline ]
[ Time Frame: Week 56 ]
[ Time Frame: Week 104 ]
[ Time Frame: Baseline ]
[ Time Frame: Week 48 ]
[ Time Frame: Week 112 ]
[ Time Frame: Final Visit (up to 224 weeks of OLE FD phase) ] |
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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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
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 | No |
E.8.6.3 | Specify the countries outside of the EEA in which trial sites are planned |
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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 |