Juvenile Idiopathic Arthritis MedDRA version: 23.1 Level: PT Classification code 10059176 Term: Juvenile idiopathic arthritis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders
Conditions
Sponsors
sanofi-aventis recherche & développement
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: -Male and female patients aged =1 and =17 years (or country specified age requirement, 12-17 years for Russia) 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 antirheumatic drug (DMARD) as per Investigator's judgment. Are the trial subjects under 18? yes Number of subjects for this age range: 72 F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: -Body weight 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 dose 1 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 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. -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 central laboratory). -Severe cardiac disease due to sJIA. -Pregnant or breast-feeding female adolescent patients.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 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.;Secondary Objective: To describe the pharmacodynamics (PD) profile, the efficacy and the long term safety of sarilumab in patients with sJIA.;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);Timepoint(s) of evaluation of this end point: Up to week 12 | — |
Secondary
| Measure | Time frame |
|---|---|
| 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;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 Creactive 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 | — |
Countries
Argentina, Bulgaria, Canada, Chile, Czech Republic, Estonia, Finland, France, Germany, Ireland, Italy, Mexico, Netherlands, Poland, Russian Federation, Spain, United Kingdom, United States
Outcome results
None listed