Clinical trial NCT04483700: Study to Evaluate the Efficacy and Safety of Filgotinib in Participants With Active Ankylosing Spondylitis Who Are Naive to Biologic Disease-Modifying Antirheumatic Drug Therapy
Official title: A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Filgotinib in Subjects With Active Ankylosing Spondylitis Who Are Naive to Biologic Disease-Modifying Antirheumatic Drug Therapy
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE3
Conditions: Ankylosing Spondylitis
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
Collaborators: name: Galapagos NV
First posted: 2020-07-23
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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 are naive to biologic disease-modifying antirheumatic drug therapy.

Detailed description: 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.

Eligibility criteria: Key Inclusion Criteria:

* Ambulatory male or female, ≥ 18 years of age (≥ 20 years of age in Japan) on the day of signing initial informed consent
* Have an established diagnosis of radiographic axial spondyloarthritis (SpA)/ ankylosing spondylitis (AS) by a rheumatologist (or other specialist with expertise 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, 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 defined by:

  * Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) ≥ 4, AND
  * Spinal pain score ≥ 4 (based on BASDAI question 2)
* Have had an inadequate response to ≥ 2 NSAIDs at a therapeutic dose range for ≥ 2 weeks each (a total duration of NSAID trial ≥ 4 weeks) or intolerance to ≥ 2 NSAIDs for the treatment of AS
* If using allowed conventional synthetic disease-modifying antirheumatic drug (csDMARD), NSAID, or corticosteroid therapy, must have been on stable doses (as outlined in protocol) prior to Day 1

Key Exclusion Criteria:

* Contraindication to magnetic resonance imaging (MRI)
* Prior exposure to a biologic disease-modifying antirheumatic drug (bioDMARD) (including investigational agents)
* 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.

Primary outcomes:
measure: Proportion of Participants Who Achieve an Assessment of SpondyloArthritis international Society 40% Improvement (ASAS40) Response at Week 16
timeFrame: Week 16
Secondary outcomes:
measure: Proportion of Participants Who Achieve an ASAS40 Response
timeFrame: Up to Week 12
measure: Proportion of Participants Who Achieve an Assessment of SpondyloArthritis international Society 20% Improvement (ASAS20) Response
timeFrame: Up to Week 16
measure: Proportion of Participants who achieve Ankylosing Spondylitis Disease Activity Score (ASDAS) Low Disease Activity (LDA) (ie, ASDAS < 2.1)
timeFrame: Week 16
measure: Proportion of Participants Who Achieve an ASAS 5/6 Response
timeFrame: Up to Week 16
measure: Change from Baseline in the Individual Components of the ASAS Core Set
timeFrame: Baseline and up to Week 16
measure: Proportion of Participants Who Achieve a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 50% Improvement Response
timeFrame: Up to Week 16
measure: Change From Baseline in ASDAS
timeFrame: Baseline and up to Week 16
measure: Change From Baseline in BASDAI
timeFrame: Baseline and up to Week 16
measure: Change From Baseline in Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI)
timeFrame: Baseline and up to Week 16
measure: Change From Baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI) (Linear Score)
timeFrame: Baseline and up to Week 16
measure: Change From Baseline in Chest Expansion
timeFrame: Baseline and up to Week 16
measure: Change From Baseline in Occiput-to-wall Distance
timeFrame: Baseline and up to Week 16
measure: Change From Baseline in Maastricht Ankylosing Spondylitis Enthesitis Score (MASES), in Participants With Enthesitis at Baseline
timeFrame: Baseline and up to Week 16
measure: Change From Baseline in Ankylosing Spondylitis Quality of Life (ASQoL)
timeFrame: Baseline and up to Week 16
measure: Change From Baseline in Assessment of SpondyloArthritis international Society Health Index (ASAS HI)
timeFrame: Baseline and up to Week 16
measure: Change From Baseline in Physical Component Summary Score (PCS) of the 36-Item Short-Form Survey (SF-36) Version 2
timeFrame: Baseline and up to Week 16
measure: Change From Baseline in Mental Component Summary Score (MCS) of the SF-36 Version 2
timeFrame: Baseline and up to Week 16
measure: Change from Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue Scale (FACIT-Fatigue)
timeFrame: Baseline and up to Week 16
measure: Change From Baseline in Work Productivity and Activity Impairment for Ankylosing Spondylitis (WPAI-AS)
timeFrame: Baseline and up to Week 16
measure: Change From Baseline in EuroQol 5 Dimensions 5 Levels (EQ-5D-5L)
timeFrame: Baseline and up to Week 16
measure: Change From Baseline in Spinal Spondyloarthritis Research Consortium of Canada (SPARCC) Score at Week 16
timeFrame: Baseline; Week 16
measure: Change From Baseline in Sacroiliac Joint (SIJ) SPARCC Score at Week 16
timeFrame: Baseline; Week 16
Other outcomes:
Locations:
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References: