A Repeated Dose-finding Study of Sarilumab in Children and Adolescents With Systemic Juvenile Idiopathic Arthritis (SKYPS)

Juvenile Idiopathic Arthritis Clinical Trial

Official title:

An Open-label, Sequential, Ascending, Repeated Dose-finding Study of Sarilumab, Administered With Subcutaneous (SC) Injection, in Children and Adolescents, Aged 1 to 17 Years, With Systemic Juvenile Idiopathic Arthritis (sJIA), Followed by an Extension Phase

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02991469
• Other study ID #: DRI13926
• Secondary ID: U1111-1177-35842
• Status: Recruiting
• Phase: Phase 2
• Start date: August 9, 2018
• Est. completion date: February 19, 2029

Study information

• Verified date: January 2024
• Source: Sanofi
• Contact: For site information, send an email with site number to
• Email: Contact-Us[@]sanofi.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Primary 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.

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 72
• Est. completion date: February 19, 2029
• Est. primary completion date: April 1, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year to 17 Years

Eligibility

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 JIA subtype according to the International Associations against Rheumatism (ILAR) 2001 Juvenile Idiopathic Arthritis (JIA) Classification Criteria

with the following features:

• 5 active joints at screening or
• 2 active joints at screening with systemic JIA fever >37.5 0C 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.
• Patient with an inadequate response to current treatment and considered as a candidate for a biologic disease modifying anti rheumatic drug (DMARD) as per investigator's judgment.

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 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 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).
• Severe cardiac disease due to sJIA.
• 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 SAR153191 (REGN88)
Pharmaceutical form: Solution Route of administration: Subcutaneous

Locations

Country	Name	City	State
Argentina	Investigational Site Number : 0320004	San Miguel de Tucumán	Tucumán
Bulgaria	Investigational Site Number : 1000001	Plovdiv
Canada	Investigational Site Number : 1240110	Calgary	Alberta
Canada	Investigational Site Number : 1240112	Montreal	Quebec
Finland	Investigational Site Number : 2460040	Helsinki
France	Investigational Site Number : 2500041	Bron
France	Investigational Site Number : 2500042	Montpellier
France	Investigational Site Number : 2500040	Paris
Germany	Investigational Site Number : 2760064	Berlin
Germany	Investigational Site Number : 2760065	Berlin
Germany	Investigational Site Number : 2760061	Bremen
Germany	Investigational Site Number : 2760062	Hamburg
Germany	Investigational Site Number : 2760060	Sankt Augustin
Germany	Investigational Site Number : 2760063	Sendenhorst
Ireland	Investigational Site Number : 3720001	Dublin
Italy	Investigational Site Number : 3800051	Genova
Italy	Investigational Site Number : 3800054	Milano
Italy	Investigational Site Number : 3800052	Roma
Russian Federation	Investigational Site Number : 6430001	Moscow
Russian Federation	Investigational Site Number : 6430062	Moscow
Russian Federation	Investigational Site Number : 6430063	Moscow
Russian Federation	Investigational Site Number : 6430065	Ufa
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 : 8260034	Leeds
United Kingdom	Investigational Site Number : 8260033	Liverpool
United Kingdom	Investigational Site Number : 8260031	London	London, City Of

Sponsors (2)

Lead Sponsor	Collaborator
Sanofi	Regeneron Pharmaceuticals

Countries where clinical trial is conducted

Argentina,  Bulgaria,  Canada,  Finland,  France,  Germany,  Ireland,  Italy,  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 12. Extension phase: Up to Week 162
Secondary	Number of patients with local site reactions		Core treatment phase: Up to Week 12. Extension phase: Up to Week 156
Secondary	Juvenile Idiopathic Arthritis ACR30/50/70/90/100 (in the absence of fever) response rate		Core treatment phase: Up to Week 12. Extension phase: At weeks 24, 48, and every 24 weeks up to Week 156
Secondary	Change from baseline in JIA ACR component: Physician's global assessment of disease activity		Core treatment phase: Up to Week 12. Extension phase: At weeks 24, 48, and every 24 weeks up to Week 156
Secondary	Change from baseline in JIA ACR Component: Patient / parent assessment of overall well-being		Core treatment phase: Up to Week 12. Extension phase: At weeks 24, 48, and every 24 weeks up to Week 156
Secondary	Change from baseline in JIA ACR Component: Childhood Health Assessment Questionnaire (CHAQ) - Disability Index		Core treatment phase: Up to Week 12. Extension phase: At weeks 24, 48, and every 24 weeks up to Week 156
Secondary	Change from baseline in JIA ACR Component: Number of joints with active arthritis		Core treatment phase: Up to Week 12. Extension phase: At weeks 24, 48, and every 24 weeks up to Week 156
Secondary	Change from baseline in JIA ACR Component: Number of joints with limitation of motion		Core treatment phase: Up to Week 12. Extension phase: At weeks 24, 48, and every 24 weeks up to Week 156
Secondary	Change from baseline in JIA ACR Component: High sensitivity C-reactive protein (hs-CRP)		Core treatment phase: Up to Week 12. Extension phase: At weeks 24, 48, and every 24 weeks up to Week 156
Secondary	Change from baseline in JIA ACR Component: fever		Core treatment phase: Up to Week 12. Extension phase: At weeks 24, 48, and every 24 weeks up to Week 156
Secondary	Change from baseline in Juvenile Arthritis Disease Activity Score-27 (JADAS)		Core treatment phase: Up to Week 12. Extension phase: At weeks 24, 48, and every 24 weeks up to Week 156
Secondary	Changes in glucocorticoid use		Core treatment phase: Up to Week 12. Extension phase: Up to Week 156
Secondary	Changes in IL-6 associated biomarkers: IL6		Up to Week 12
Secondary	Changes in IL-6 associated biomarkers: sIL-6R		Up to Week 12
Secondary	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)		At weeks 24, 48, and every 24 weeks up to Week 156
Secondary	Proportion of patients free of glucocorticoids and without JIA flare		At weeks 24, 48, and every 24 weeks up to Week 156