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

Juvenile Idiopathic Arthritis Clinical Trial

— SKYPP  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02776735
• Other study ID #: DRI13925
• Secondary ID: U1111-1177-34872
• Status: Completed
• Phase: Phase 2
• Start date: September 6, 2016
• Est. completion date: December 27, 2023

Study information

• Verified date: February 2024
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Primary Objective: 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 adequate treatment of this population Secondary Objective: To describe the pharmacodynamic (PD) profile, the efficacy and the long-term safety of sarilumab in patients with pcJIA.

Description:

For approximately 72 patients enrolled in the dose-finding and second portions, the total study duration per patient will be 166 weeks that will consist 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 approximately 28 patients enrolled in the third portion, the total study duration per patient will be 106 weeks that will consist of a 4- week screening, a 12-week core treatment phase, a 84-week extension phase, and a 6-week post-treatment follow-up.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 102
• Est. completion date: December 27, 2023
• Est. primary completion date: April 8, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years to 17 Years

Eligibility

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 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
• 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

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

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Juvenile
• Juvenile Idiopathic Arthritis

Intervention

Drug:
• Sarilumab
Pharmaceutical form:Solution Route of administration: Subcutaneous

Locations

Country	Name	City	State
Argentina	Investigational Site Number : 0320060	Caba	Buenos Aires
Argentina	Investigational Site Number : 0320004	Tucumán
Canada	Investigational Site Number : 1240112	Montréal	Quebec
Chile	Investigational Site Number : 1520016	Concepcion	Biobío
Czechia	Investigational Site Number : 2030041	Brno
Finland	Investigational Site Number : 2460040	Helsinki
France	Investigational Site Number : 2500040	Paris
Germany	Investigational Site Number : 2760064	Berlin
Germany	Investigational Site Number : 2760061	Bremen
Germany	Investigational Site Number : 2760062	Hamburg
Germany	Investigational Site Number : 2760060	Sankt Augustin
Italy	Investigational Site Number : 3800052	Roma
Mexico	Investigational Site Number : 4840061	Guadalajara	Jalisco
Mexico	Investigational Site Number : 4840060	Monterrey	Nuevo León
Netherlands	Investigational Site Number : 5280020	Utrecht
Poland	Investigational Site Number : 6160074	Bydgoszcz	Kujawsko-pomorskie
Poland	Investigational Site Number : 6160073	Krakow	Malopolskie
Poland	Investigational Site Number : 6160071	Lodz	Lódzkie
Poland	Investigational Site Number : 6160070	Lublin	Lubuskie
Poland	Investigational Site Number : 6160072	Sosnowiec	Slaskie
Russian Federation	Investigational Site Number : 6430001	Moscow
Russian Federation	Investigational Site Number : 6430062	Moscow
Russian Federation	Investigational Site Number : 6430063	Moscow
Spain	Investigational Site Number : 7240050	Esplugues de Llobregat	Catalunya [Cataluña]
Spain	Investigational Site Number : 7240052	Madrid	Madrid, Comunidad De
Spain	Investigational Site Number : 7240053	Madrid
Spain	Investigational Site Number : 7240051	Valencia
United Kingdom	Investigational Site Number : 8260033	Liverpool
United Kingdom	Investigational Site Number : 8260031	London	London, City Of
United States	Children's Hospital Los Angeles Site Number : 8400416	Los Angeles	California

Sponsors (2)

Lead Sponsor	Collaborator
Sanofi	Regeneron Pharmaceuticals

Countries where clinical trial is conducted

United States,  Argentina,  Canada,  Chile,  Czechia,  Finland,  France,  Germany,  Italy,  Mexico,  Netherlands,  Poland,  Russian Federation,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Assessment of PK parameter: maximum serum concentration observed (Cmax)		Up to Week 12
Primary	Assessment of PK parameter: Area under the serum concentration versus time curve calculated using the trapezoidal method during a dose interval (AUC0-t)		Up to Week 12
Primary	Assessment of PK parameter: Concentration observed before treatment administration during repeated dosing (Ctrough)		Up to Week 12
Secondary	Number of patients with adverse events		Core treatment phase: Up to Week(W) 12. Extension phase: Up to end of study (W162 for dose-finding and second portions or W102 for third portion)
Secondary	Number of patients with local site reactions		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)
Secondary	Juvenile Idiopathic Arthritis (JIA ACR) 30/50/70/90/100 response rate		Core treatment phase: Up to Week 12. Extension phase: up to W156 for dose-finding and second portions or W96 for third portion
Secondary	Change from baseline in JIA ACR Component: Physician's global assessment of disease activity		Core treatment phase: Up to Week 12. Extension phase: up to W156 for dose-finding and second portions or W96 for third portion
Secondary	Change from baseline in JIA ACR Component: Patient / parent assessment of overall well-being		Core treatment phase: Up to Week 12. Extension phase: up to W156 for dose-finding and second portions or W96 for third portion
Secondary	Change from baseline in JIA ACR Component: Childhood Health Assessment Questionnaire (CHAQ) - Disability Index		Core treatment phase: Up to Week 12. Extension phase: up to W156 for dose-finding and second portions or W96 for third portion
Secondary	Change from baseline in JIA ACR Component: Number of joints with active arthritis		Core treatment phase: Up to Week 12. Extension phase: up to W156 for dose-finding and second portions or W96 for third portion
Secondary	Change from baseline in JIA ACR Component: Number of joints with limitation of motion		Core treatment phase: Up to Week 12. Extension phase: up to W156 for dose-finding and second portions or W96 for third portion
Secondary	Change from baseline in JIA ACR Component: High sensitivity C-reactive protein (hs-CRP)		Core treatment phase: Up to Week 12. Extension phase: up to W156 for dose-finding and second portions or W96 for third portion
Secondary	Change from baseline in Juvenile Arthritis Disease Activity Score-27 (JADAS)		Core treatment phase: Up to Week 12. Extension phase: up to W156 for dose-finding and second portions or W96 for third portion
Secondary	Change in IL-6 associated biomarkers: IL6		Up to Week 12
Secondary	Change in IL-6 associated biomarkers: sIL-6R		Up to Week 12