Study to Evaluate the Efficacy and Safety of Filgotinib in Participants With Active Ankylosing Spondylitis Who Have an Inadequate Response to Biologic Disease-Modifying Antirheumatic Drug Therapy

Gilead Sciences

Overview

The primary objective of this study is to evaluate the effect of filgotinib versus placebo on signs and symptoms of active ankylosing spondylitis (AS), evaluated by Assessment of SpondyloArthritis international Society 40% improvement (ASAS40) response at Week 16 in participants with active AS who have an inadequate response to biologic disease-modifying antirheumatic drug therapy.

The study consists of 2 parts: Main Study (screening through Week 16) and Long-Term Extension (LTE) (up to 1.5 years after Week 16). Participants who permanently discontinue treatment in the Main Study will not be eligible for the Long-Term extension.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Conditions

Ankylosing Spondylitis

Interventions

FilgotinibDRUG

Tablets administered orally once daily

Placebo to Match FilgotinibDRUG

Tablets administered orally once daily

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Key Inclusion Criteria: * Ambulatory male or female individuals who are ≥ 18 years of age (≥ 20 years of age in Japan) on the day of signing informed consent * Have had inadequate response or intolerance to at least 1 and not more than 3 biologic disease-modifying antirheumatic drugs (bioDMARDs) administered for the treatment of ankylosing spondylitis (AS) or inflammatory arthritis * Have an established diagnosis of radiographic axial spondyloarthritis (SpA)/ AS by a rheumatologist (or other specialist with expertise in diagnosing AS) * Meet Assessment of SpondyloArthritis international Society (ASAS) classification criteria for axial SpA with radiographic sacroiliitis on imaging at screening as follows: * History of back pain ≥ 3 months and age at onset of back pain \< 45 years, AND * Radiographic sacroiliitis Grade ≥ 2 bilaterally or Grade 3-4 unilaterally, AND * ≥ 1 SpA feature (refer to protocol; inflammatory back pain, arthritis, heel enthesitis, uveitis anterior, dactylitis, psoriasis, inflammatory bowel disease (IBD), good response to nonsteroidal anti-inflammatory drugs (NSAIDs), family history of SpA, historically positive human leukocyte antigen B27 (HLA-B27), elevated C-reactive protein (CRP)) * Have active AS at screening and Day 1 as defined by: * Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) ≥ 4, AND * Spinal pain ≥ 4 (based on BASDAI question 2) * Have a history of inadequate response or intolerance to NSAIDs for the treatment of AS * If using allowed conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), NSAID, or corticosteroid therapy, must have been on stable doses (as outlined in protocol) prior to Day 1 Key Exclusion Criteria: * Prior exposure to a Janus kinase (JAK) inhibitor \> 2 doses * Total ankylosis of the spine * Any active/recent infection, as specified in the protocol * Diagnosis of fibromyalgia * Any musculoskeletal disorder other than AS that would interfere with assessment of study parameters, as per judgement of investigator * Note: Prior history of reactive or other types of inflammatory arthritis is permitted if there is documentation of change in diagnosis to AS or additional diagnosis of AS * Any history of an inflammatory arthritis with onset age before 16 years old Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Outcomes

Primary Outcomes

Proportion of Participants Who Achieve an Assessment of SpondyloArthritis international Society 40% Improvement (ASAS40) Response at Week 16

The ASAS40 calculation involves the analysis of 4 domains: participant's global assessment of disease activity, spinal pain (derived from the spinal pain questionnaire), function (derived from Bath Ankylosing Spondylitis Functional Index (BASFI) score), and inflammation (derived from morning stiffness questions from Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)). The ASAS40 is achieved if there is an improvement of ≥ 40% and ≥ 2 units in at least 3 domains on a scale of 10 with no worsening in the remaining domain.

Time frame: Week 16

Secondary Outcomes

Proportion of Participants Who Achieve an ASAS40 Response

The ASAS40 calculation involves the analysis of 4 domains: participant's global assessment of disease activity, spinal pain (derived from the spinal pain questionnaire), function (derived from BASFI score), and inflammation (derived from morning stiffness questions from BASDAI). The ASAS40 is achieved if there is an improvement of ≥ 40% and ≥ 2 units in at least 3 domains on a scale of 10 with no worsening in the remaining domain.

Time frame: Up to Week 12

Proportion of Participants Who Achieve an Assessment of SpondyloArthritis international Society 20% Improvement (ASAS20) Response

The ASAS20 calculation involves the analysis of 4 domains: participant's global assessment of disease activity, spinal pain (derived from the spinal pain questionnaire), function (derived from BASFI score), and inflammation (derived from morning stiffness questions from BASDAI).The ASAS20 is achieved if there is an improvement of ≥ 20% and ≥ 1 units in at least 3 domains on a scale of 10 with no worsening of ≥ 20% and ≥ 1 unit in the remaining domain.

Time frame: Up to Week 16

Proportion of Participants who achieve Ankylosing Spondylitis Disease Activity Score (ASDAS) Low Disease Activity (LDA) (ie, ASDAS < 2.1) at Week 16

Data from ClinicalTrials.gov

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ASDAS is a composite score of 5 domains: total back pain, peripheral pain and/or swelling, duration of morning stiffness (derived from BASDAI questionnaire), participant's global assessment of disease activity, and serum high-sensitivity C-reactive protein (hsCRP). The ASDAS has a continuous scale from 0 with no defined upper end. A lower score indicate lower disease activity. ASDAS LDA is achieved when ASDAS \< 2.1.

Proportion of Participants Who Achieve an ASAS 5/6 Response

The ASAS 5/6 is achieved when at least 20% improvement in at least 5 out of 6 domains. The 6 domains to use are: participant's global assessment of disease activity, spinal pain (derived from the spinal pain questionnaire), function (derived from BASFI score), inflammation (derived from morning stiffness questions from BASDAI), lateral spinal flexion (Bath Ankylosing Spondylitis Metrology Index (BASMI) question 1), and hsCRP.

Time frame: Up to Week 16

Change from Baseline in the Individual Components of the ASAS Core Set

ASAS core set consists of 6 assessment domains: (1) participant's global assessment of disease activity, (2) spinal pain (derived from the spinal pain questionnaire), (3) function (derived from BASFI score), (4) inflammation (derived from morning stiffness questions from BASDAI), (5) hsCRP, (for these 5 domains, a lower score indicate lower disease activity) and (6) lateral spinal flexion (BASMI question 1) (for this 6th domain; a higher score indicate lower disease activity).