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

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

Overview

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.

Detailed 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.

Interventions

• Drug Sarilumab SAR153191 (REGN88)
  Pharmaceutical form: Solution Route of administration: Subcutaneous

Primary outcome measures

• Assessment of PK parameter: maximum serum concentration observed (Cmax) [Time frame: Up to Week 12]
• Assessment of PK parameter: Area under the serum concentration versus time curve calculated using the trapezoidal method during a dose interval (AUC0-t) [Time frame: Up to Week 12]
• Assessment of PK parameter: Concentration observed before treatment administration during repeated dosing (Ctrough) [Time frame: Up to Week 12]

Secondary outcome measures (11)

• Number of patients with adverse events [Time frame: Core treatment phase: Up to Week 12. Extension phase: Up to Week 162]
• Proportion of participants with local reactions after injection [Time frame: Core treatment phase: Up to Week 12. Extension phase: Up to Week 156]
• Proportion of participants with Investigator Global Assessment (IGA) of disease activity below a defined value on 1-100 VAS scale [Time frame: Core treatment phase: Up to Week 12. Extension phase: At weeks 24, 48, and every 24 weeks up to Week 156]
• Proportion of participants with Parent / patient Global Assessment (PGA) of well-being below a defined value on 1-100 VAS scale [Time frame: Core treatment phase: Up to Week 12. Extension phase: At weeks 24, 48, and every 24 weeks up to Week 156]
• Proportion of participants with clinically inactive disease (CID) [Time frame: Core treatment phase: Up to Week 12. Extension phase: At weeks 24, 48, and every 24 weeks up to Week 156]
• Changes in glucocorticoid use [Time frame: Core treatment phase: Up to Week 12. Extension phase: At weeks 24, 48, and every 24 weeks up to Week 156]
• Juvenile Idiopathic Arthritis ACR30/50/70/90/100 (in the absence of fever) response rate [Time frame: Core treatment phase: Up to Week 12. Extension phase: At weeks 24, 48, and every 24 weeks up to Week 156]
• Change from baseline in individual JIA ACR components [Time frame: Core treatment phase: Up to Week 12. Extension phase: At weeks 24, 48, and every 24 weeks up to Week 156]
• Change from baseline in Systemic Juvenile Arthritis Disease Activity Score-10 (sJADAS-10) [Time frame: Core treatment phase: Up to Week 12. Extension phase: At weeks 24, 48, and every 24 weeks up to Week 156]
• Assessment of participants with disease-related symptoms [Time frame: At Week 4]
• Changes in IL-6 associated biomarkers [Time frame: Up to Week 12]

Eligibility criteria

Inclusion criteria

• Male and female patients aged ≥1 and ≤17 years (or country specified age requirement, ≥6 to ≤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 OR According to 2024 EULAR/PReS recommendation at Screening.
• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Spain · 6 centers

• Investigational Site Number : 7240055 — Barcelona
• Investigational Site Number : 7240050 — Esplugues de Llobregat
• Investigational Site Number : 7240053 — Madrid
• Investigational Site Number : 7240056 — Madrid
• Investigational Site Number : 7240054 — Málaga
• Investigational Site Number : 7240051 — Valencia

Germany · 5 centers

• Investigational Site Number : 2760064 — Berlin
• Investigational Site Number : 2760065 — Berlin
• Investigational Site Number : 2760062 — Hamburg
• Investigational Site Number : 2760060 — Sankt Augustin
• Investigational Site Number : 2760063 — Sendenhorst

Russia · 4 centers

• Investigational Site Number : 6430001 — Moscow
• Investigational Site Number : 6430062 — Moscow
• Investigational Site Number : 6430063 — Moscow
• Investigational Site Number : 6430065 — Ufa

France · 3 centers

• Investigational Site Number : 2500041 — Bron
• Investigational Site Number : 2500042 — Montpellier
• Investigational Site Number : 2500040 — Paris

Italy · 3 centers

• Investigational Site Number : 3800051 — Genoa
• Investigational Site Number : 3800054 — Milan
• Investigational Site Number : 3800052 — Rome

United Kingdom · 3 centers

• Investigational Site Number : 8260031 — London
• Investigational Site Number : 8260034 — Leeds
• Investigational Site Number : 8260033 — Liverpool

Argentina · 2 centers

• Investigational Site Number : 0320004 — San Miguel de Tucumán
• Investigational Site Number : 0320005 — Buenos Aires

Greece · 2 centers

• Investigational Site Number : 3000001 — Athens
• Investigational Site Number : 3000002 — Thessaloniki

Canada · 1 center

• Investigational Site Number : 1240110 — Calgary

Finland · 1 center

• Investigational Site Number : 2460040 — Helsinki

Ireland · 1 center

• Investigational Site Number : 3720001 — Crumlin

Portugal · 1 center

• Investigational Site Number : 6200003 — Lisbon

Identifiers

NCT: NCT02991469 · DRI13926 · U1111-1177-3584 · 2024-512701-11

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗