An Open-label, Ascending, Repeated Dose-finding Study of Sarilumab in Children and Adolescents With Polyarticular-course Juvenile Idiopathic Arthritis (pcJIA)

NCT02776735 | Completed Phase 2 Results DMC FDA Drug

• 3 other identifiers: DRI13925U1111-1177-34872015-003999-79
• Study Type: interventional
• Target: 102
• Locations: 15 countries
• Sites: 30

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.

Conditions

Juvenile Idiopathic Arthritis

Outcome Measures

Primary Outcomes (3)

• Maximum Serum Concentration (Cmax) of Sarilumab at Week 12

  The Cmax was defined as maximum serum concentration. The values reported are mean and standard deviation.

  Pre-dose on Days 1, 3, 5, 8, 12 and Weeks 2, 4, 8 and 12

• Area Under the Serum Concentration Versus Time Curve Using the Trapezoidal Method During a Dose Interval (AUC0-t) of Sarilumab at Week 12

  The AUC0-t was defined as area under the concentration in serum versus time curve calculated using the trapezoidal method during a dose interval (tau). The values reported are mean and standard deviation.

  Pre-dose on Days 1, 3, 5, 8, 12 and Weeks 2, 4, 8 and 12

• Concentration Before Treatment Administration During Repeated Dosing (Ctrough) of Sarilumab at Week 12

  The Ctrough was defined as concentration observed before treatment administration during repeated dosing from baseline to Week 12. The values reported are mean and standard deviation.

  Pre-dose on Days 1, 3, 5, 8, 12 and Weeks 2, 4, 8 and 12

Secondary Outcomes (30)

• Cohorts 1 and 3: Change From Baseline in High-Sensitivity C-reactive Protein (Hs-CRP) at Week 12

  Baseline (Day 1) and Week 12

• Cohort 2: Change From Baseline in High-Sensitivity C-reactive Protein at Weeks 12, 24, 48, 96, and 156

  Baseline (Day 1) and Weeks 12, 24, 48, 96, and 156

• Change From Baseline in Interleukin-6 (IL-6) at Week 12

  Baseline (Day 1) and Week 12

• Change From Baseline in Total Soluble Interleukin-6 Receptor (sIL-6R) at Week 12

  Baseline (Day 1) and Week 12

• Cohorts 1 and 3: Percentage of Participants With Juvenile Idiopatic Arthritis American College of Rheumatology (JIA ACR) 30 Response at Week 12

  Week 12

Study Arms (1)

Sarilumab

EXPERIMENTAL

Participants received one of three ascending dose regimens of sarilumab by subcutaneous (SC) injection based on body weight. All the participants received the selected dose regimen once this was identified. Sarilumab was given during 12-week core treatment phase followed by an extension treatment phase (144 weeks for 73 participants enrolled in dose-finding and second portions and 84 weeks for approximately 29 participants enrolled in third portion)

Drug: Sarilumab

Interventions

Sarilumab DRUG

Pharmaceutical form:Solution Route of administration: Subcutaneous

Also known as: SAR153191 (REGN88)

Sarilumab

Eligibility Criteria

• Age: 2 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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.
• 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.
• 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.

Sponsors & Collaborators

• Sanofi: lead
• Regeneron Pharmaceuticals: collaborator

Study Sites (30)

Children's Hospital Los Angeles Site Number : 8400416

Los Angeles, California, 90027, United States

Location

Investigational Site Number : 0320060

CABA, Buenos Aires, C1270AAN, Argentina

Location

Investigational Site Number : 0320004

San Miguel de Tucumán, T4000AXL, Argentina

Location

Investigational Site Number : 1240112

Montreal, Quebec, H3T1C5, Canada

Location

Investigational Site Number : 1520016

Concepción, Región del Biobío, Chile

Location

Investigational Site Number : 2030041

Brno, 62500, Czechia

Location

Investigational Site Number : 2460040

Helsinki, 00029 HUS, Finland

Location

Investigational Site Number : 2500040

Paris, 75015, France

Location

Investigational Site Number : 2760064

Berlin, 13125, Germany

Location

Investigational Site Number : 2760061

Bremen, 28205, Germany

Location

Investigational Site Number : 2760062

Hamburg, 22081, Germany

Location

Investigational Site Number : 2760060

Sankt Augustin, 53757, Germany

Location

Investigational Site Number : 3800052

Roma, Italy

Location

Investigational Site Number : 4840061

Guadalajara, Jalisco, 44620, Mexico

Location

Investigational Site Number : 4840060

Monterrey, Nuevo León, 64460, Mexico

Location

Investigational Site Number : 5280020

Utrecht, 3584 EA, Netherlands

Location

Investigational Site Number : 6160074

Bydgoszcz, Kuyavian-Pomeranian Voivodeship, 85-667, Poland

Location

Investigational Site Number : 6160073

Krakow, Lesser Poland Voivodeship, 31-503, Poland

Location

Investigational Site Number : 6160070

Lublin, Lubusz Voivodeship, 20-093, Poland

Location

Investigational Site Number : 6160071

Lodz, Lódzkie, 91-738, Poland

Location

Investigational Site Number : 6160072

Sosnowiec, Silesian Voivodeship, 41-218, Poland

Location

Investigational Site Number : 6430001

Moscow, 115522, Russia

Location

Investigational Site Number : 6430062

Moscow, 117198, Russia

Location

Investigational Site Number : 6430063

Moscow, 119991, Russia

Location

Investigational Site Number : 7240050

Esplugues de Llobregat, Catalunya [Cataluña], 08950, Spain

Location

Investigational Site Number : 7240052

Madrid, Madrid, Comunidad de, 28046, Spain

Location

Investigational Site Number : 7240053

Madrid, 28009, Spain

Location

Investigational Site Number : 7240051

Valencia, 46026, Spain

Location

Investigational Site Number : 8260031

London, London, City of, WC1N 3JH, United Kingdom

Location

Investigational Site Number : 8260033

Liverpool, L12 2AP, United Kingdom

Location

MeSH Terms

Conditions

Arthritis, Juvenile

Interventions

sarilumab

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Results Point of Contact

• Title: Trial Transparency Team
• Organization: Sanofi aventis recherche & développement

Contact-US@sanofi.com

800-633-1610

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 16, 2016
• First Posted: May 18, 2016
• Study Start: September 6, 2016
• Primary Completion: April 8, 2022
• Study Completion: December 27, 2023
• Last Updated: October 15, 2024
• Results First Posted: October 15, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will share

Locations

AR (2); CA (1); FR (1); CL (1); ES (4); ME (2); RU (3); PL (5); CZ (1); DE (4); FI (1); NL (1); GB (2); US (1); IT (1)