Safety, Tolerability, Pharmacokinetics, and Efficacy of Filgotinib for the Treatment of Polyarticular-course Juvenile Idiopathic Arthritis in Children and Adolescents

Official title

Multicenter, Open-label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of Filgotinib in Children and Adolescents From 8 Years to Less Than 18 Years of Age With Polyarticular-course Juvenile Idiopathic Arthritis

Overview

This is a multicenter Phase 3, open-label, single-arm study to evaluate the safety, tolerability, PK, and efficacy of orally administered filgotinib for up to 18 weeks.

Interventions

• Drug Filgotinib
  IP will be provided as commercially developed film-coated tablets or age-appropriate film- coated tablets for use in paediatric subjects aged at least 8 years and needs to be taken orally q.d. at approximately the same time every morning (with or without food)

Primary outcome measures

• Frequency and severity of treatment-emergent adverse events (TEAEs), treatment-emergent serious adverse events (SAEs), and TEAEs leading to treatment discontinuation [Time frame: From baseline (Day 1) the study up to Week 22]

Secondary outcome measures (9)

• Percentage of subjects with juvenile idiopathic arthritis (JIA) American College of Rheumatology (ACR) 30 response [Time frame: Week 12 and Week 18]
• Percentage of subjects with JIA ACR inactive disease [Time frame: Week 12 and Week 18]
• Change from baseline in Juvenile Arthritis Disease Activity Score (JADAS)-27 erythrocyte sedimentation rate (ESR) [Time frame: Week 12 and Week 18]
• Change from baseline in Juvenile Arthritis Disease Activity Score JADAS-27 C-reactive protein (CRP) [Time frame: Week 12 and Week 18]
• Incidence of uveitis at various timepoints (including occurrence, type, and severity) [Time frame: Week 1, Week 4, Week 8, Week 12, Week 18]
• PK parameters of filgotinib and its primary metabolite GS-829845 including maximum observed plasma concentration at steady-state [Cmax,ss] [Time frame: Week 4, Week 12 and Week 18]
• PK parameters of filgotinib and its primary metabolite GS-829845 including area under the plasma concentration-time curve over the dosing interval at steady-state [AUC0-24,ss] [Time frame: Week 4, Week 12 and Week 18]
• PK parameters of filgotinib and its primary metabolite GS-829845 including area under the plasma concentration-time curve over the dosing interval at steady-state for the effective exposure [AUCeff,ss] [Time frame: Week 4, Week 12 and Week 18]
• Acceptability of the age-appropriate pediatric formulation and the adult commercially developed film-coated tablet formulation assessed by Pediatric Oral Medicine Acceptability Questionnaire for Patients (POMAQ-P) [Time frame: Week 4 and Week 18]

Eligibility criteria

Inclusion criteria

• Subject and/or parent/legal guardian must be able and willing to comply with the clinical study protocol requirements and must sign and date the ICF and assent (if required per local regulation) as approved by the Independent Ethics Committee / Institutional Review Board, prior to any screening evaluations.
• Female or male subject 8 to <18 years of age, on the date of signing the informed consent and assent (per local regulation) form.
• Subject must meet the ILAR classification and have moderately to severely active disease for one of the following categories that is not adequately controlled with his/her current therapy (see Protocol Appendix 1 for disease activity assessment criteria):

• Extended oligoarthritis (i.e. affecting a total of more than 4 joints after the first 6 months of disease)
• RF-positive polyarthritis
• RF-negative polyarthritis
• PsA
• ERA
• Subject with intolerance or a history of inadequate response to at least one of the following medications for the treatment of pJIA, administered for at least 3 months, based on current treatment guidelines: conventional synthetic disease modifying anti rheumatic drugs (csDMARDs; including methotrexate) and/or biologic disease modifying anti-rheumatic drugs (bDMARDs) administered per local label, and/or non steroidal anti-inflammatory drugs for ERA and PsA subtypes.
• Female subject of childbearing potential who is sexually active and at risk for pregnancy must agree to use contraception/preventive exposure measures as described in the protocol.

Exclusion criteria

• Subject with a body weight <15 kg.
• Subject with persistent oligoarthritis (i.e. affecting not more than 4 joints throughout the disease course).
• Subject with undifferentiated arthritis.
• Subject with anterior uveitis (active or uncontrolled) ≤12 weeks prior to baseline.
• Subject with systemic JIA.
• Subject with any other rheumatic disease, inflammatory, or immunologic disease (e.g. inflammatory bowel disease, hypogammaglobulinemia, or systemic lupus erythematosus).
• Subject has any condition or circumstances (including abnormalities in laboratory parameters) that, in the opinion of the investigator, may make a subject unlikely or unable to complete the study or comply with study procedures and requirements.
• Subject has an active infection. • Subject with a history of complicated herpes zoster infection (with multi dermatomal, disseminated, ophthalmic, or central nervous system involvement).

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

Poland · 3 centers

• Centrum Medyczne Hipokrates S C Elzbieta I Grzegorz Grzesk — Bydgoszcz
• MICS Centrum Medyczne Torun — Torun
• ETG JustMed — Warsaw

United Kingdom · 3 centers

• Bristol Royal Hospital for Children — Bristol
• Leicester Royal Infirmary — Leicester
• Nottingham University Hospitals Queen's Medical Centre — Nottingham

Germany · 2 centers

• Charité - Campus Virchow-Klinikum — Berlin
• Hamburger Zentrum fuer Kinder und Jugendrheumatologie — Hamburg

Belgium · 1 center

• UZ Leuven — Leuven

Czechia · 1 center

• Vseobecna fakultni nemocnice v Praze — Prague

France · 1 center

• Hôpital Bicêtre — Le Kremlin-Bicêtre

Hungary · 1 center

• Pecsi Tudomanyegyetem Klinikai Kozpont — Pécs

Italy · 1 center

• Istituto Giannina Gaslini-Ospedale Pediatrico IRCCS — Genova

Spain · 1 center

• Hospital Sant Joan de Deu — Barcelona

Identifiers

NCT: NCT07554495 · GLPG0634-CL-329 · 2024-511593-70-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗