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

Sanofi

Status and phase: Enrolling; Phase 2

Conditions: Juvenile Idiopathic Arthritis

Treatments: Drug: Sarilumab SAR153191 (REGN88)

Study type: Interventional

Funder types: Industry

Identifiers

NCT02991469

DRI13926

2024-512701-11 (Registry Identifier)

U1111-1177-3584 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 72 estimated patients

Sex: All

Ages: 1 to 17 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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72 participants in 1 patient group

Sarilumab

Experimental group

Description:

Participants will receive one of two ascending doses (or an additional intermediate dose based on available data) of sarilumab by subcutaneous (SC) injection based on body weight. All the participants will receive the selected dose once the selected dose is identified. Sarilumab will be given during 12-week core treatment phase followed by a 144- week extension treatment phase.

Treatment:

Drug: Sarilumab SAR153191 (REGN88)