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

NCT04483700 | Withdrawn Phase 3 DMC FDA Drug

• 2 other identifiers: GS-US-433-53072019-004279-38
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Ankylosing Spondylitis

Outcome Measures

Primary Outcomes (1)

• 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.

  Week 16

Secondary Outcomes (22)

• Proportion of Participants Who Achieve an ASAS40 Response

  Up to Week 12

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

  Up to Week 16

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

  Week 16

• Proportion of Participants Who Achieve an ASAS 5/6 Response

  Up to Week 16

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

  Baseline and up to Week 16

Study Arms (5)

Filgotinib 200 mg (Main Study - Blinded)

EXPERIMENTAL

Participants will receive filgotinib 200 mg + placebo to match (PTM) filgotinib 100 mg for up to 16 weeks.

Drug: Filgotinib; Drug: Placebo to Match Filgotinib

Filgotinib 100 mg (Main Study - Blinded)

EXPERIMENTAL

Participants will receive filgotinib 100 mg + PTM filgotinib 200 mg for up to 16 weeks.

Drug: Filgotinib; Drug: Placebo to Match Filgotinib

Placebo (Main Study - Blinded)

PLACEBO COMPARATOR

Participants will receive PTM filgotinib 200 mg + PTM filgotinib 100 mg for up to 16 weeks.

Drug: Placebo to Match Filgotinib

Filgotinib 200 mg (LTE)

EXPERIMENTAL

Before study-wide unblinding, participants will receive filgotinib 200 mg + PTM filgotinib 100 mg. After study-wide unblinding, participants will receive filgotinib 200 mg.

Drug: Filgotinib; Drug: Placebo to Match Filgotinib

Filgotinib 100 mg (LTE)

EXPERIMENTAL

Before study-wide unblinding, participants will receive filgotinib 100 mg + PTM filgotinib 200 mg. After study-wide unblinding, participants will receive filgotinib 100 mg.

Drug: Filgotinib; Drug: Placebo to Match Filgotinib

Interventions

Filgotinib DRUG

Tablets administered orally once daily

Also known as: GS-6034, GLPG0634

Filgotinib 100 mg (LTE); Filgotinib 100 mg (Main Study - Blinded); Filgotinib 200 mg (LTE); Filgotinib 200 mg (Main Study - Blinded)

Placebo to Match Filgotinib DRUG

Tablets administered orally once daily

Filgotinib 100 mg (LTE); Filgotinib 100 mg (Main Study - Blinded); Filgotinib 200 mg (LTE); Filgotinib 200 mg (Main Study - Blinded); Placebo (Main Study - Blinded)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Gilead Sciences: lead
• Galapagos NV: collaborator

MeSH Terms

Conditions

Spondylitis, Ankylosing

Interventions

GLPG0634

Condition Hierarchy (Ancestors)

Axial Spondyloarthritis; Spondylarthropathies; Spondylarthritis; Spondylitis; Spinal Diseases; Bone Diseases; Musculoskeletal Diseases; Ankylosis; Joint Diseases; Arthritis

Study Officials

• Gilead Study Director

  Gilead Sciences

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 20, 2020
• First Posted: July 23, 2020
• Study Start: December 1, 2020
• Primary Completion: October 1, 2022
• Study Completion: June 1, 2024
• Last Updated: January 11, 2021

Record last verified: 2021-01

Data Sharing

• IPD Sharing: Will not share