E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Juvenile idiopathic arthritis |
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E.1.1.1 | Medical condition in easily understood language |
Juvenile idiopathic arthritis |
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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 | 18.1 |
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 describe the pharmacokinetic (PK) profile of sarilumab in patients with pcJIA in order to identify the dose and regimen for continued development in this population. |
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E.2.2 | Secondary objectives of the trial |
To describe:
-The pharmacodynamic (PD) profile, the efficacy and the safety of sarilumab in patients with pcJIA.
-The long-term safety of sarilumab in patients with pcJIA. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
-Male and female patients aged ≥2 and ≤17 years at the time of the screening visit.
-Diagnosis of rheumatoid factor-negative or rheumatoid factor positive polyarticular Juvenile Idiopathic Arhtritis (JIA) subtype or oligoarticular extended JIA subtype according to the International League of Associations for Rheumatology (ILAR) 2001 Juvenile Idiopathic Arthritis Classification Criteria with at least 5 active joints as per American College of Rheumatology (ACR) definition for “active arthritis” at screening.
-Patient with an inadequate response to current treatment and considered as a candidate for a biologic disease-modifying antirheumatic drug (DMARD) as per Investigator’s judgment.
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E.4 | Principal exclusion criteria |
-Body weight <10 kg or >60 kg.
-If nonsteroidal anti-inflammatory drugs (NSAIDs, including cyclo-oxygenase-2 inhibitors [COX-2]) taken, dose stable for less than 2 weeks prior to the baseline visit and/or dosing prescribed outside of approved label.
-If non-biologic DMARD taken, dose stable for less than 6 weeks prior to the baseline visit or at a dose exceeding the recommended dose as per local labeling.
-If oral glucocorticoid taken, dose exceeding equivalent prednisone dose 0.5 mg/kg/day (or 30 mg/day) within 2 weeks prior to baseline.
-Prior treatment with anti-interleukin 6 (IL-6) or IL-6 receptor (IL-6R) antagonist therapies, including but not limited to tocilizumab or sarilumab.
-Treatment with any biologic DMARD within 5 half-lives prior to the first dose of sarilumab
-Treatment with a Janus kinase inhibitor within 4 weeks prior to the first dose of sarilumab
-Treatment with any investigational biologic or non-biologic product within 8 weeks or 5 half-lives prior to baseline, whichever is longer.
-Active tuberculosis patients or latent tuberculosis patients without adequate treatment.
-Exclusion criteria related to past or current infection other than tuberculosis.
-Any live, attenuated vaccine within 4 weeks prior to the baseline, such as varicella-zoster, oral polio, rubella vaccines.
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E.5 End points |
E.5.1 | Primary end point(s) |
Assessment of PK parameter: maximum serum concentration observed (Cmax)
Assessment of PK parameter: Area under the serum concentration versus time curve calculated using the trapezoidal method during a dose interval (AUC0-t)
Assessment of PK parameter: Concentration observed before treatment administration during repeated dosing (Ctrough) |
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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) |
1- Number of patients with adverse events
2- Number of patients with local site reactions
3- Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology 30 (ACR30) response rate
4- Change from baseline in individual JIA ACR components
5- Changes in IL-6 associated biomarkers
6- Number of patients with adverse events
7- Number of patients with local site reactions
8- Change from baseline in individual JIA ACR components |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1-5: Up to week 12
6-8: Up to week 104 |
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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 | Yes |
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) | Yes |
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 |
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 |
Canada |
Chile |
Czech Republic |
Estonia |
Finland |
France |
Germany |
Italy |
Mexico |
Netherlands |
Poland |
Russian Federation |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.2 | In all countries concerned by the trial years | 3 |