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

• Filgotinib (Drug): 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 outcomes

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

Secondary outcomes

• Percentage of subjects with juvenile idiopathic arthritis (JIA) American College of Rheumatology (ACR) 30 response [Week 12 and Week 18]
• Percentage of subjects with JIA ACR inactive disease [Week 12 and Week 18]
• Change from baseline in Juvenile Arthritis Disease Activity Score (JADAS)-27 erythrocyte sedimentation rate (ESR) [Week 12 and Week 18]
• Change from baseline in Juvenile Arthritis Disease Activity Score JADAS-27 C-reactive protein (CRP) [Week 12 and Week 18]
• Incidence of uveitis at various timepoints (including occurrence, type, and severity) [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] [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] [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] [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) [Week 4 and Week 18]

Sex: All, ages: 8 Years to 18 Years

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).

• Catherine Vincent, Study director, Alfasigma S.p.A.