E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Active systemic manifestations of Systemic Juvenile Idiopathic Arthritis (SJIA) |
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E.1.1.1 | Medical condition in easily understood language |
SJIA is a disease that causes swelling in the joints and inflammation in other parts of the body in children. Symptoms include fevers, rash and joint pain. |
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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 | 14.1 |
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 |
This two-part study will assess the sustained efficacy of canakinumab in the double-blind Part II and the ability to taper steroids in the open label Part I. |
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E.2.2 | Secondary objectives of the trial | |
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
•Confirmed diagnosis of systemic juvenile idiopathic arthritis as per ILAR definition that must have occurred at least 2 months prior to enrollment with onset of disease < 16 years of age.
-Arthritis in one or more joints with or preceded by fever of at least 2 weeks duration that is documented to be daily for at least 3 days with accompanying symptoms
• Active disease at the time of enrollment defined as follows:
◦ At least 2 joints with active arthritis (using ACR definition of active joint)
◦ Documented spiking, intermittent fever (body temperature > 38oC) for at least 1 day during the screening period within 1 week before first study drug dose
◦ C-reactive protein > 30 mg/L (normal range < 10 mg/L)
• No concomitant use of second line agents such as disease-modifying and/ or immunosuppressive drugs will be allowed with the exception of:
◦ Stable dose of methotrexate for at least 8 weeks prior to the screening visit, and/or folic/folinic acid per standard medical practice
◦ Stable dose of no more than one non-steroidal anti-inflammatory drug for at least 2 weeks prior to the screening visit
◦ Stable dose of steroid treatment < or = to 1.0 mg/kg/day in 1-2 doses per day of oral prednisone or equivalent
Other protocol-defined inclusion criteria may apply. |
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E.4 | Principal exclusion criteria |
• Diagnosis of active macrophage-activation syndrome (MAS) within the last 6 months
• Risk factors for tuberculosis
• Patients with active or recurrent bacterial, fungal or viral infection at the time of enrollment, including patients with evidence of HIV infection, Hepatitis B and Hepatitis C infection
Other protocol-defined exclusion criteria may apply. |
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Time to flare in Part II
2. Proportion of patients who were on steroids at entry into Part I and who were able to taper steroid as per protocol. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. During part II, which is event driven (total duration - TBD)
2. Maximum duration of Part I 32 weeks |
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E.5.2 | Secondary end point(s) |
1. Maintenance of adapted ACR Pediatric 30/50/70/90/100 criteria during Part II
2. Change in disability over time by CHAQ
3. Change in health related quality of life over time by CHQ-PF50
4. Proportion of patients who reached a steroid dose < or = 0.2 mg/kg at end of Part Ic
5. Steroid level at end of Part Ic and change from baseline to end of Part Ic |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. During part II, which is event driven (total duration - TBD)
2. Over the length of the event driven study (total duration - TBD)
3. During part II, which is event driven (total duration - TBD)
4. Maximum duration of Part I 32 weeks
5. Maximum duration of Part I 32 weeks |
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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 | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | Yes |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
tolerability and immunogenicity |
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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 | 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 II: event-driven withdrawal design |
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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 |
Argentina |
Brazil |
Canada |
Israel |
Peru |
Switzerland |
Turkey |
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 | 2 |
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 |