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

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

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

Первичные конечные точки

• Assessment of PK parameter: maximum serum concentration observed (Cmax) [Срок оценки: 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) [Срок оценки: Up to Week 12]
• Assessment of PK parameter: Concentration observed before treatment administration during repeated dosing (Ctrough) [Срок оценки: Up to Week 12]

Вторичные конечные точки (11)

• Number of patients with adverse events [Срок оценки: Core treatment phase: Up to Week 12. Extension phase: Up to Week 162]
• Proportion of participants with local reactions after injection [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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) [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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) [Срок оценки: 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 [Срок оценки: At Week 4]
• Changes in IL-6 associated biomarkers [Срок оценки: Up to Week 12]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Испания · 6 центров

• 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

Германия · 5 центров

• 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

Россия · 4 центра

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

Франция · 3 центра

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

Италия · 3 центра

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

Великобритания · 3 центра

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

Аргентина · 2 центра

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

Греция · 2 центра

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

Канада · 1 центр

• Investigational Site Number : 1240110 — Calgary

Финляндия · 1 центр

• Investigational Site Number : 2460040 — Helsinki

Ирландия · 1 центр

• Investigational Site Number : 3720001 — Crumlin

Португалия · 1 центр

• Investigational Site Number : 6200003 — Lisbon

Идентификаторы

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

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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