E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Systemic Juvenile Idiopathic Arthritis (sJIA) |
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E.1.1.1 | Medical condition in easily understood language |
Children with sJIA have arthritis and often have daily fever with rash, in addition to inflammation of the lining of the lung or heart, liver or spleen enlargement, or enlargement of the lymph nodes. |
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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 | 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 |
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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 |
Part I: Primary Objectives:
1. To assess the efficacy of tocilizumab versus placebo in combination with stable ongoing therapy, with regard to signs and symptoms in sJIA patients with persistent activity and an inadequate response to NSAIDs and systemic corticosteroids.
2. To evaluate the short term safety of tocilizumab versus placebo in combination with stable ongoing therapy, with regard to adverse events and laboratory assessments in patients with sJIA with persistent activity and an inadequate response to NSAIDs and corticosteroids.
Part II: Primary Objectives:
1. To evaluate the safety of tocilizumab in chronic administration;
2. To assess the effect of tocilizumab to enable the reduction or elimination of corticosteroids
Part III: Primary Objectives
1. To assess the long-term safety of 8 mg/kg tocilizumab in children > 30 kg and 12 mg/kg tocilizumab in children < 30 kg with regard to adverse events and laboratory result abnormalities;
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E.2.2 | Secondary objectives of the trial |
Part I
1. To assess the efficacy of tocilizumab versus placebo in combination with stable ongoing therapy, with regard to common systemic features in sJIA patients with persistent activity and an inadequate response to NSAIDs and corticosteroids;
2. To assess the efficacy of treatment with tocilizumab to permit concomitant corticosteroid reduction;
Part II
1. To assess the durability and magnitude of the tocilizumab efficacy response in patients with sJIA including meeting the definition of inactive disease and clinical remission;
2. To assess the efficacy of treatment with tocilizumab to permit concomitant medication reductions;
Part III:
1. To assess the efficacy of treatment with tocilizumab to permit concomitant medication reductions (corticosteroids, methotrexate, NSAIDs);
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• patients aged 2 - 17 years of age;
• systemic JIA with >= 6 months persistent activity;
• presence of active disease (>=5 active joints, or >=2 active joints + fever + steroids);
• inadequate clinical response to NSAIDs and corticosteroids due to toxicity or lack of efficacy. |
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E.4 | Principal exclusion criteria |
• wheelchair bound or bed-ridden;
• any other autoimmune, rheumatic disease or overlap syndrome other than sJIA;
• intravenous long-acting corticosteroids or intra-articular corticosteroids within 4 weeks of baseline, or throughout study;
• DMARDs (other than methotrexate);
• previous treatment with tocilizumab.
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary endpoint:
The proportion of patients with at least 30% improvement in JIA
core set (JIA ACR30 response) at week 12 (JIA Core Set assessed
in comparison to baseline) and absence of fever*
*Absence of fever is defined as no temperature measurement ≥ 37.5° C.
in the preceding seven days |
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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) |
Proportion of patients with JIA core set ACR 30/50/70/90 response [ Time Frame: Week 12 ]
Mean percent change in JIA core set ACR score [ Time Frame: Week 12 ]
Proportion of patients with fever [ Time Frame: Week 12 ]
Change in laboratory indicators (hsCRP, Hb, platelets, leukocytes) [ Time Frame: Week 12 ]
Concomitant corticosteroid reduction [ Time Frame: Week 12 ]
Immunogenicity: anti-tocilizumab antibodies (HAHA) [ Time Frame: 260 weeks ]
Pharmacokinetics/Pharmacodynamics: tocilizumab, Interleukin-6 (IL-6), sIL-6R [ Time Frame: 260 weeks ]
Concomitant medication reduction (corticosteroids, methotrexate, NSAIDs) [ Time Frame: 260 weeks ]
Duration of response (inactive disease, clinical remission) [ Time Frame: 260 weeks ]
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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 | 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 | 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 | Yes |
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 |
The trial involves single site in the Member State concerned
| Information not present in EudraCT |
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 | 26 |
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 |
Czech Republic |
Germany |
Greece |
Italy |
Mexico |
Netherlands |
Norway |
Poland |
Slovakia |
Spain |
United Kingdom |
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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The end of the study will occur when the last participating patient completes the last scheduled visit of Part III, or when the sponsor decides to discontinue the development
program. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 6 |
E.8.9.2 | In all countries concerned by the trial months | 1 |
E.8.9.2 | In all countries concerned by the trial days | 0 |