E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Active Polyarticular Juvenile Idiopathic Arthritis (pJIA) |
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E.1.1.1 | Medical condition in easily understood language |
Active Polyarticular Juvenile Idiopathic Arthritis (pJIA) |
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E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 23.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10059176 |
E.1.2 | Term | Juvenile idiopathic arthritis |
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 |
To estimate abatacept steady-state trough concentration (Cmin) at Day 113 in children and adolescents with pJIA aged 6 to 17. |
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E.2.2 | Secondary objectives of the trial |
1. Proportion of subjects achieving ACR Pediatric 30 at Day 113 in 6-17 year old subjects.
2. Abatacept Cmin at Day 57, Day 85, and Day 113 during the initial 4-month short term period by each weight-tiered dosing regimen in 6-17 year old subjects.
3. Safety summary (proportion of subjects with adverse events, deaths, SAEs, and AEs leading to discontinuation) during initial 4-month short-term and long-term extension periods in both age cohorts.
4. Proportion of subjects with positive immunogenicity response during initial 4 month and long-term extension periods and up to 6 months following discontinuation of treatment in both age cohorts.
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
PK sub-study described in the main Protocol (Section 5.5): An exploratory sub study in approximately 60 subjects of the 6-17 year old cohort will be performed for the purpose of Cmin estimation as well as population PK (PPK) analysis.
Site specific Protocol Amendment 12 dated 02-July-2015: The primary objective of this substudy is to assess the presence of protective antibody titers to diphtheria and tetanus in pediatric subjects (2-5 years of age) with pJIA after receiving at least two continuous months (56 days) of a stable dose of SC abatacept. |
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E.3 | Principal inclusion criteria |
1.JIA subjects (male or female), ages 2-17 years with active disease who had an insufficient therapeutic response (for at least 3 months) or prior or intolerance to at least one non biologic DMARD or TNFa antagonists
2. Subjects with TNFa inadequate response (or prior biologic) will be restricted to 30% of the population
3. Subjects must have a history of at least 5 joints with active disease and must have currently active articular disease with ≥ 2 active joints and ≥ 2 joints with limitation of motion. |
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E.4 | Principal exclusion criteria |
1. Subjects with other rheumatic diseases or major chronic inflammatory/immunologic diseases, active uveitis, systemic JIA with active systemic features (within a period of 6 months prior to enrollment), persistent Oligoarthritis JIA, or failed 3 or more TNFa antagonists or other biological DMARDS will be excluded.
(Subjects with enthesitis related arthritis or psoriatic arthritis (PsA) can be included)
2. Active systemic disease: (ie, extra-articular features of systemic JIA including fever, rash, organomegaly) within a period of 6 months prior to randomization.
3. Subjects who have failed more than two TNFa antagonists or other biologic DMARDs
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is abatacept steady state Cmin at Day 113 in 6-17 year old subjects |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Day 113 / end of 4 month short term period |
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E.5.2 | Secondary end point(s) |
1. Proportion of subjects achieving ACR Pediatric 30 at Day 113 in 6-17 year old subjects.
2. Abatacept Cmin at Day 57, Day 85, and Day 113 during the initial 4-month short term period by each weight-tiered dosing regimen in 6-17 year old subjects.
3. Safety summary (proportion of subjects with adverse events, deaths, SAEs, and AEs leading to discontinuation) during initial 4-month short-term and long-term extension periods in both age cohorts.
4. Proportion of subjects with positive immunogenicity response during initial 4 month and long-term extension periods and up to 6 months following discontinuation of treatment in both age cohorts.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Day 113
2. Day 57 / Day85 / Day 113
3. Short and Long term
4. Short, Long Term and Follow up
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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 | Yes |
E.6.13.1 | Other scope of the trial description |
Immunogenicity Anti-BMS-188667 Antibody testing for all subjects still active in the IM101-301 5-Year Extension. |
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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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
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 | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
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 |
Argentina |
Brazil |
Mexico |
Peru |
Russian Federation |
South Africa |
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 | 9 |
E.8.9.2 | In all countries concerned by the trial months | 10 |
E.8.9.2 | In all countries concerned by the trial days | 0 |