Clinical trial NCT02776735: An Open-label, Ascending, Repeated Dose-finding Study of Sarilumab in Children and Adolescents With Polyarticular-course Juvenile Idiopathic Arthritis (pcJIA)
Official title: An Open-label, Sequential, Ascending, Repeated Dose-finding Study of Sarilumab, Administered With Subcutaneous (SC) Injection, in Children and Adolescents, Aged 2 to 17 Years, With Polyarticular-course Juvenile Idiopathic Arthritis (pcJIA) Followed by an Extension Phase
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Juvenile Idiopathic Arthritis
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
Collaborators: name: Regeneron Pharmaceuticals
First posted: 2016-05-18
Enrollment: 102
Sex: ALL
Minimum age (years): 2
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Primary Objective:

To describe the pharmacokinetic (PK) profile of sarilumab in participants aged 2-17 years with Polyarticular-course Juvenile Idiopathic Arthritis (pcJIA) in order to identify the dose and regimen for adequate treatment of this population

Secondary Objective:

To describe the pharmacodynamic (PD) profile, the efficacy and the long-term safety of sarilumab in participants with pcJIA.

Detailed description: For 73 participants enrolled in the dose-finding and second portions, the total study duration per participant was up to 166 weeks that consists of a 4- week screening, a 12-week core treatment phase, a 144-week extension phase, and a 6-week post-treatment follow-up. For 29 participants enrolled in the third portion, the total study duration per participant was up to 106 weeks that consists of a 4- week screening, a 12-week core treatment phase, a 84-week extension phase, and a 6-week post-treatment follow-up.

Eligibility criteria: Inclusion criteria :

* Male and female participants 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 Arthritis (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
* Participant 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

Exclusion criteria:

* Body weight \<10 kg or \>60 kg for participants enrolled in the 3 ascending dose cohorts, then body weight \<10 kg for participants subsequently enrolled at the selected dose-regimen.
* If nonsteroidal anti-inflammatory drugs (NSAIDs) \[including cyclo oxygenase-2 inhibitors (COX-2)\] taken, dose stable for \<2 weeks prior to the baseline visit and/or dosing prescribed outside of approved label.
* If non-biologic DMARD taken, dose stable for \<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 treatment for pcJIA 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 visit, 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 participants.

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Primary outcomes:
measure: Maximum Serum Concentration (Cmax) of Sarilumab at Week 12
timeFrame: Pre-dose on Days 1, 3, 5, 8, 12 and Weeks 2, 4, 8 and 12
measure: Area Under the Serum Concentration Versus Time Curve Using the Trapezoidal Method During a Dose Interval (AUC0-t) of Sarilumab at Week 12
timeFrame: Pre-dose on Days 1, 3, 5, 8, 12 and Weeks 2, 4, 8 and 12
measure: Concentration Before Treatment Administration During Repeated Dosing (Ctrough) of Sarilumab at Week 12
timeFrame: Pre-dose on Days 1, 3, 5, 8, 12 and Weeks 2, 4, 8 and 12
Secondary outcomes:
measure: Cohorts 1 and 3: Change From Baseline in High-Sensitivity C-reactive Protein (Hs-CRP) at Week 12
timeFrame: Baseline (Day 1) and Week 12
measure: Cohort 2: Change From Baseline in High-Sensitivity C-reactive Protein at Weeks 12, 24, 48, 96, and 156
timeFrame: Baseline (Day 1) and Weeks 12, 24, 48, 96, and 156
measure: Change From Baseline in Interleukin-6 (IL-6) at Week 12
timeFrame: Baseline (Day 1) and Week 12
measure: Change From Baseline in Total Soluble Interleukin-6 Receptor (sIL-6R) at Week 12
timeFrame: Baseline (Day 1) and Week 12
measure: Cohorts 1 and 3: Percentage of Participants With Juvenile Idiopatic Arthritis American College of Rheumatology (JIA ACR) 30 Response at Week 12
timeFrame: Week 12
measure: Cohort 2: Percentage of Participants With Juvenile Idiopatic Arthritis American College of Rheumatology 30 Response at Weeks 12, 24, 48, 96, and 156
timeFrame: Weeks 12, 24, 48, 96, and 156
measure: Cohorts 1 and 3: Percentage of Participants With Juvenile Idiopatic Arthritis American College of Rheumatology 50 Response at Week 12
timeFrame: Week 12
measure: Cohort 2: Percentage of Participants With Juvenile Idiopatic Arthritis American College of Rheumatology 50 Response at Weeks 12, 24, 48, 96, and 156
timeFrame: Weeks 12, 24, 48, 96, and 156
measure: Cohorts 1 and 3: Percentage of Participants With Juvenile Idiopatic Arthritis American College of Rheumatology 70 Response at Week 12
timeFrame: Week 12
measure: Cohort 2: Percentage of Participants With Juvenile Idiopatic Arthritis American College of Rheumatology 70 Response at Weeks 12, 24, 48, 96, and 156
timeFrame: Weeks 12, 24, 48, 96, and 156
measure: Cohorts 1 and 3: Percentage of Participants With Juvenile Idiopatic Arthritis American College of Rheumatology 90 Response at Week 12
timeFrame: Week 12
measure: Cohort 2: Percentage of Participants With Juvenile Idiopatic Arthritis American College of Rheumatology 90 Response at Weeks 12, 24, 48, 96, and 156
timeFrame: Weeks 12, 24, 48, 96, and 156
measure: Cohorts 1 and 3: Percentage of Participants With Juvenile Idiopatic Arthritis American College of Rheumatology 100 Response at Week 12
timeFrame: Week 12
measure: Cohort 2: Percentage of Participants With Juvenile Idiopatic Arthritis American College of Rheumatology 100 Response at Weeks 12, 24, 48, 96, and 156
timeFrame: Weeks 12, 24, 48, 96, and 156
measure: Cohorts 1 and 3: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, Activity Joint Count-71, at Week 12
timeFrame: Baseline (Day 1) and Week 12
measure: Cohort 2: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, Activity Joint Count-71, at Weeks 12, 24, 48, 96, and 156
timeFrame: Baseline (Day 1) and Weeks 12, 24, 48, 96, and 156
measure: Cohorts 1 and 3: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, Limited Motion Joint Count, at Week 12
timeFrame: Baseline (Day 1) and Week 12
measure: Cohort 2: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, Limited Motion Joint Count, at Weeks 12, 24, 48, 96, and 156
timeFrame: Baseline (Day 1) and Weeks 12, 24, 48, 96, and 156
measure: Cohorts 1 and 3: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, Childhood Health Assessment Questionnaire Disability Index, at Week 12
timeFrame: Baseline (Day 1) and Week 12
measure: Cohort 2: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, Childhood Health Assessment Questionnaire Disability Index, at Weeks 12, 24, 48, 96, and 156
timeFrame: Baseline (Day 1) and Weeks 12, 24, 48, 96, and 156
measure: Cohorts 1 and 3: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, C-Reactive Protein, at Week 12
timeFrame: Baseline (Day 1) and Week 12
measure: Cohort 2: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, C-Reactive Protein, at Weeks 12, 24, 48, 96, and 156
timeFrame: Baseline (Day 1) and Weeks 12, 24, 48, 96, and 156
measure: Cohorts 1 and 3: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, Physician Global Assessment of Disease Activity, at Week 12
timeFrame: Baseline (Day 1) and Week 12
measure: Cohort 2: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, Physician Global Assessment of Disease Activity, at Weeks 12, 24, 48, 96, and 156
timeFrame: Baseline (Day 1) and Weeks 12, 24, 48, 96, and 156
measure: Cohorts 1 and 3: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, Participant/Parent Assessment of Overall Well-Being, at Week 12
timeFrame: Baseline (Day 1) and Week 12
measure: Cohort 2: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, Participant/Parent Assessment of Overall Well-Being, at Weeks 12, 24, 48, 96, and 156
timeFrame: Baseline (Day 1) and Weeks 12, 24, 48, 96, and 156
measure: Cohorts 1 and 3: Mean Change From Baseline in Juvenile Arthritis Disease Activity Score (JADAS-27) at Week 12
timeFrame: Baseline (Day 1) and Week 12
measure: Cohort 2: Mean Change From Baseline in Juvenile Arthritis Disease Activity Score at Weeks 12, 24, 48, 96, and 156
timeFrame: Baseline (Day 1) and Weeks 12, 24, 48, 96, and 156
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (SAEs)
timeFrame: From the first administration of study treatment (Day 1) up to end of treatment period, maximum of 156 weeks for portions 1 and 2 and 96 weeks for portion 3
measure: Number of Participants With Local Site Reactions
timeFrame: From the first administration of study treatment (Day 1) up to end of treatment period, maximum of 156 weeks for portions 1 and 2 and 96 weeks for portion 3
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Children's Hospital Los Angeles Site Number : 8400416
state: California
city: Caba
country: Argentina
facility: Investigational Site Number : 0320060
state: Buenos Aires
city: Tucumán
country: Argentina
facility: Investigational Site Number : 0320004
city: Montréal
country: Canada
facility: Investigational Site Number : 1240112
state: Quebec
city: Concepcion
country: Chile
facility: Investigational Site Number : 1520016
state: Biobío
city: Brno
country: Czechia
facility: Investigational Site Number : 2030041
city: Helsinki
country: Finland
facility: Investigational Site Number : 2460040
city: Paris
country: France
facility: Investigational Site Number : 2500040
city: Berlin
country: Germany
facility: Investigational Site Number : 2760064
city: Bremen
country: Germany
facility: Investigational Site Number : 2760061
city: Hamburg
country: Germany
facility: Investigational Site Number : 2760062
city: Sankt Augustin
country: Germany
facility: Investigational Site Number : 2760060
city: Roma
country: Italy
facility: Investigational Site Number : 3800052
city: Guadalajara
country: Mexico
facility: Investigational Site Number : 4840061
state: Jalisco
city: Monterrey
country: Mexico
facility: Investigational Site Number : 4840060
state: Nuevo León
city: Utrecht
country: Netherlands
facility: Investigational Site Number : 5280020
city: Bydgoszcz
country: Poland
facility: Investigational Site Number : 6160074
state: Kujawsko-pomorskie
city: Lublin
country: Poland
facility: Investigational Site Number : 6160070
state: Lubuskie
city: Lodz
country: Poland
facility: Investigational Site Number : 6160071
state: Lódzkie
city: Krakow
country: Poland
facility: Investigational Site Number : 6160073
state: Malopolskie
city: Sosnowiec
country: Poland
facility: Investigational Site Number : 6160072
state: Slaskie
city: Moscow
country: Russian Federation
facility: Investigational Site Number : 6430001
city: Moscow
country: Russian Federation
facility: Investigational Site Number : 6430062
city: Moscow
country: Russian Federation
facility: Investigational Site Number : 6430063
city: Esplugues de Llobregat
country: Spain
facility: Investigational Site Number : 7240050
state: Catalunya [Cataluña]
city: Madrid
country: Spain
facility: Investigational Site Number : 7240052
state: Madrid, Comunidad De
city: Madrid
country: Spain
facility: Investigational Site Number : 7240053
city: Valencia
country: Spain
facility: Investigational Site Number : 7240051
city: London
country: United Kingdom
facility: Investigational Site Number : 8260031
state: London, City Of
city: Liverpool
country: United Kingdom
facility: Investigational Site Number : 8260033
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: