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 | 18.0 |
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 |
Primary Objective - To characterize the pharmacokinetics of subcutaneous tocilizumab (SC TCZ) in patients with sJIA - To evaluate the pharmacodynamics of SC TCZ in patients with sJIA - To evaluate the safety of SC TCZ in patients with sJIA |
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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 |
- Ages 1 (12 for patients in Russia) year up to and including 17 years at screening - Diagnosis of systemic juvenile idiopathic arthritis - Inadequate clinical response (in the opinion of the treating physician) to non-steroidal anti-inflammatory drugs (NSAIDs) and corticosteroids - Concurrent treatment with disease-modifying anti-rheumatic drugs (DMARDs) (including methotrexate [MTX]), NSAIDs, and oral corticosteroids is permitted at the discretion of the investigator. - Discontinuation of biologic agents (other than tocilizumab if the patient is receiving IV TCZ) for 4 days -20 weeks prior to baseline depending on biologic agent - Female patients of childbearing potential and male patients with a female partner of childbearing potential must agree with the required contraceptive methods as defined per protocol. |
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E.4 | Principal exclusion criteria |
- Prior discontinuation of IV TCZ because of inadequate clinical response or safety events - Patients with poorly controlled disease (in the opinion of the treating physician) despite current treatment with IV TCZ - sJIA that is well controlled by any treatment agent other than TCZ (Juvenile Arthritis Disease Activity Score (JADAS) -71≤3.8 with no fever) - Patients who are wheelchair-bound or bedridden - Any other auto-immune, rheumatic disease, or overlapping syndrome other than sJIA - Prior stem cell transplant at any time |
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E.5 End points |
E.5.1 | Primary end point(s) |
- Serum TCZ concentration and population PK model-predicted PK exposures area under the concentration−time curve (AUC) , maximum plasma concentration (Cmax ) and Cmin) for the initial QW and Q10D dosing regimens at steady state, and the Q2W dosing regimen at steady state in the <30 kg patients - Serum IL-6 and soluble IL-6R (sIL-6R) levels, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) - The incidence and severity of adverse events (including local injection-site reactions) and serious adverse events - The incidence and severity of adverse events of special interest - The incidence and severity of clinical laboratory abnormalities - The incidence of anti-TCZ antibodies |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
- Pharmacokinetic endpoints will be evaluated at fixed timepoints during the first 14 weeks of the study [Weeks 0-14] - Pharmacodynamic endpoints will be evaluated at fixed timepoints during the first 14 weeks of the study [Weeks 0-14] - Adverse events, adverse events of special interest and clinical laboratory abnormalities will be recorded for the entire duration of the study [Weeks 0-52] - The presence of anti-TCZ antibodies will be evaluated at baseline and at regular intervals with event-driven testing in cases of anaphylaxis, serious hypersensitivity events, or any hypersensitivity event (including non-serious events) leading to treatment withdrawal (at the time of the event and at least 8 weeks after the event) |
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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 | No |
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) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
dose evaluation in paediatric patients (adaptive design) |
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E.7.2 | Therapeutic exploratory (Phase II) | No |
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 | No |
E.8.1.1 | Randomised | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
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.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 13 |
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 |
Brazil |
Canada |
France |
Germany |
Italy |
Mexico |
Russian Federation |
Spain |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
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 patient completes the last scheduled visit of the study or if the sponsor decides, for whatever reason, to discontinue the study |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 15 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 8 |
E.8.9.2 | In all countries concerned by the trial days | 3 |