E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Polyarticular-course juvenile idiopathic arthritis |
|
E.1.1.1 | Medical condition in easily understood language |
Childhood arthritis in several joints |
|
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 | 13.1 |
E.1.2 | Level | LLT |
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 |
|
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 |
Primary Objective (from Part II)
To compare the proportion of patients on tocilizumab versus placebo who develop a JIA ACR30 flare (compared to week 16) by week 40. |
|
E.2.2 | Secondary objectives of the trial |
• To evaluate the efficacy of open-label tocilizumab therapy (Part I),
• To evaluate the long-term effect of tocilizumab on the maintenance of clinical response and safety in patients with pcJIA (Part III)
• To evaluate the efficacy and safety of 8 mg/kg vs 10 mg/kg in patients < 30 kg (Parts I, II and III) |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
children/juveniles, 2-17 years of age
polyarticular-course juvenile idiopathic arthritis (pcJIA) >/=6 months duration
active disease (>/=5 active joints, >/=3 with limitation of motion)
inadequate response to or inability to tolerate methotrexate
methotrexate, oral corticosteroids and NSAIDs at stable dose (at least 8, 4 and 2 weeks, respectively) prior to and including baseline
biologics discontinued, between at least 1 and 20 weeks prior to and including baseline, depending on biologic |
|
E.4 | Principal exclusion criteria |
auto-immune, rheumatic disease or overlap syndrome other than polyarticular-course JIA
wheelchair bound or bedridden
intraarticular, intramuscular, intravenous or long-acting corticosteroids within 4 weeks prior to and including baseline
DMARDs (other than methotrexate) within 4 weeks prior to and including baseline
previous treatment with tocilizumab
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
Part II
Proportion of patients who develop a JIA ACR30 flare (relative to week 16) in the period from week 16 up to and including week 40. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
First JIA ACR30 flare between visit weeks 16 and 40. |
|
E.5.2 | Secondary end point(s) |
• Proportion of patients with JIA ACR30/50/70/90 responses at week 40.
• Mean absolute change from baseline in each component of the JIA core set at week 40.
• Mean absolute change from baseline in pain VAS at week 40.
• Proportion of patients with inactive disease at week 40.
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
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 | Yes |
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, QoL Assessments |
|
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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Part I: lead in period; Part II: randomized double blind; Part III: open-label |
|
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 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 31 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Argentina |
Australia |
Belgium |
Brazil |
Canada |
France |
Germany |
Italy |
Mexico |
Peru |
Poland |
Russian Federation |
Spain |
United Kingdom |
United States |
|
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
|
The study will end when the last participating patient completes the last scheduled visit of Part III, or when the sponsor decides to discontinue the development program. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |