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 | 20.0 |
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 |
To describe the pharmacokinetic (PK) profile of sarilumab in patients aged 1-17 years with Systemic Juvenile Idiopathic Arthritis (sJIA) in order to identify the dose and regimen for adequate treatment of this population. |
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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 sJIA. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
-Male and female patients aged ≥1 and ≤17 years at the time of the screening visit.
-Diagnosis of systemic Juvenile Idiopathic Arthritis (JIA) subtype according to the International Associations against Rheumatism (ILAR) 2001 Juvenile Idiopathic Arthritis Classification Criteria with the following features:
-≥5 active joints at screening or;
-≥2 active joints at screening with systemic JIA fever >37.5 °C in the 3 days preceding baseline or for at least 3 out of any 7 consecutive days during screening despite glucocorticoids at a dose stable for at least 3 days.
-Patients with an inadequate response to current treatment and considered as a candidate for a biologic disease modifying antirheumaticdrug (DMARD) as per Investigator's judgment.
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E.4 | Principal exclusion criteria |
-Body weight <10 kg or >60 kg for patients enrolled in the ascending dose cohorts, then body weight < 10 kg for patients subsequently enrolled at the selected dose.
-Uncontrolled severe systemic symptoms and/or Macrophage Activation Syndrome (MAS) within 6 months prior to screening.
-History of or ongoing interstitial lung disease, pulmonary hypertension, pulmonary alveolar proteinosis.
-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 dose1 mg/kg/day (or 60 mg/day) within 3 days 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 treatment for sJIA within 5 half-lives prior to the first dose of sarilumab (the required off treatment periods and procedures may vary according to local requirements).
-Treatment with a Janus kinase inhibitor within 4 weeks prior to the firstdose 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.
-Exclusion related to tuberculosis.
-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 centrallaboratory).
-Severe cardiac disease due to sJIA.
-Pregnant or breast-feeding female adolescent patients. |
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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 adverse events
2- Acceptability assessments (local tolerability)
3- Juvenile Idiopathic Arthritis ACR30/50/70/90/100 (in the absence of fever) 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 C-reactive protein (hs-CRP)
10- Change from baseline in JIA ACR Component: fever
11- Juvenile Arthritis Disease Activity Score-27 (JADAS) change from baseline
12- Changes in glucocorticoid use
13- Changes in IL-6 associated biomarkers : IL6
14- Changes in IL-6 associated biomarkers : sIL-6 R
15- Proportion of patients receiving glucocorticoids by dose category (glucocorticoid equivalent prednisone dose ≥0.5 mg/kg, ≥0.2 mg/kg and <0.5 mg/kg, <0.2 mg/kg)
16- Proportion of patients free of glucocorticoids and without JIA flare |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1: Core treatment phase: Up to week 12; Extension phase: Up to week 162
2: Core treatment phase: Up to week 12; Extension phase: Up to week 156
3-11:Core treatment phase: Up to week 12; Extension phase: At weeks 24, 48, and every 24 weeks up to Week 156
12- Core treatment phase: Up to Week 12; Extension phase: Up to Week 156
13-14: Up to week 12
15-16: At weeks 24, 48, and every 24 weeks up to Week 156 |
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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 | 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.8.2.4 | Number of treatment arms in the trial | 1 |
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 | 33 |
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 |
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.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 3 |