E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Juvenile idiopathic arthritis |
|
E.1.1.1 | Medical condition in easily understood language |
Juvenile idiopathic arthritis |
|
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 | 21.0 |
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 |
|
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
aged 2-17 years with Polyarticular-course Juvenile idiopathic Arthritis
(pcJIA) in order to identify the dose and regimen for continued
development in this population. |
|
E.2.2 | Secondary objectives of the trial |
To describe the pharmacodynamics (PD) profile, the efficacy and the
long term safety of sarilumab in patients with pcJIA. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
-Male and female patients aged ≥2 and ≤17 years (or country specified
age requirement) 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. |
|
E.4 | Principal exclusion criteria |
-Body weight <10 kg or >60 kg for patients enrolled in the 3 ascending
dose cohorts, then body weight <10 kg for patients subsequently enrolled at the selected dose-regimen.
-If nonsteroidal anti-inflammatory drugs (NSAIDs, including cyclooxygenase-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.
-Use of parenteral or intra-articular glucocorticoid injection within 4
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; and treatment with growth hormone within 4 weeks prior to the first dose of sarilumab (the required off treatment periods and procedures may vary according to local requirements).
-Treatment with any investigational biologic or non-biologic product
within 8 weeks or 5 half-lives prior to baseline, whichever is longer.
-Lipid lowering drug stable for less than 6 weeks prior to screening.
-Exclusion related to tuberculosis (TB).
-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. Killed or inactive vaccine may be permitted based on the Investigator's judgment.
-Exclusion related to history of a systemic hypersensitivity reaction to
any biologic drug and known hypersensitivity to any constituent of the
product.
-Laboratory abnormalities at the screening visit (identified by the central laboratory).
-Pregnant or breast-feeding female adolescent patients. |
|
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) |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
1- Number of adverse events
2- Acceptability assessments (local tolerability)
3- Juvenile Idiopathic Arthritis (JIA ACR) 30/50/70/90/100 response
rate
4- Change from baseline in JIA ACR Component: Physician's global
assessment of disease activity
5- Change from baseline in JIA ACR Component: Patient / parent
assessment of overall well-being
6- Change from baseline in JIA ACR Component: Childhood Health
Assessment Questionnaire (CHAQ) – Disability Index
7- Change from baseline in JIA ACR Component: Number of joints with
active arthritis
8- Change from baseline in JIA ACR Component: Number of joints with
limitation of motion
9- Change from baseline in JIA ACR Component: High sensitivity Creactive protein (hs-CRP)
10- Juvenile Arthritis Disease Activity Score-27 (JADAS) change from
baseline
11- Changes in IL-6 associated biomarkers
12- Changes in IL-6 associated biomarkers : sIL-6 R |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Core treatment phase: Up to Week 12 - Extension phase: Up to end of study (W162 for dose-finding and second portions or W102 for third portion)
2. Core treatment phase: Up to Week 12 - Extension phase: Up to end of treatment (W156 for dose-finding and second portions or W96 for third portion)
3 - 10. Core treatment phase: Core treatment phase: Up to Week 12 -Extension phase: up to W156 for dose-finding and second portions or W96 for third portion
11 – 12. Up to Week 12 |
|
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 | Yes |
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 |
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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 29 |
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 |
Canada |
Chile |
Czech Republic |
Estonia |
Finland |
France |
Germany |
Italy |
Mexico |
Netherlands |
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
|
|
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 | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |