AzTrials
AzTrials

Ankylosing SpondylitisPhase 3SEALION1-IRNCT04483687

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

A Phase 3 study testing Filgotinib in people with Ankylosing Spondylitis, run by Gilead Sciences.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
Search all trials

Trial 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 have an inadequate… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Ankylosing Spondylitis
What is being tested?
Filgotinib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
0 participants
Where
No sites listed yet
Study dates
Dec 2020to Sep 2024
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 12Show fewer
  • ≥ 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

Who cannot join

  • 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.

About this study

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 Have an Inadequate Response to Biologic Disease-Modifying Antirheumatic Drug Therapy

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.

Read the 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.

Being tested
Filgotinib, Placebo to Match Filgotinib
Medical subject headings
Spondylitis, Ankylosing

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • FilgotinibDrug

    Also called GS-6034, GLPG0634

    Tablets administered orally once daily

  • Placebo to Match FilgotinibDrug

    Tablets administered orally once daily

Study groups in NCT04483687
Study groupRoleWhat they receive
Filgotinib 200 mg (Main Study - Blinded)ExperimentalParticipants will receive filgotinib 200 mg + placebo to match (PTM) filgotinib 100 mg for up to 16 weeks.
Receives: Drug: Filgotinib; Drug: Placebo to Match Filgotinib
Filgotinib 100 mg (Main Study - Blinded)ExperimentalParticipants will receive filgotinib 100 mg + PTM filgotinib 200 mg for up to 16 weeks.
Receives: Drug: Filgotinib; Drug: Placebo to Match Filgotinib
Placebo (Main Study - Blinded)Placebo comparatorParticipants will receive PTM filgotinib 200 mg + PTM filgotinib 100 mg for up to 16 weeks.
Receives: Drug: Placebo to Match Filgotinib
Filgotinib 200 mg (LTE)ExperimentalBefore study-wide unblinding, participants will receive filgotinib 200 mg + PTM filgotinib 100 mg. After study-wide unblinding, participants will receive filgotinib 200 mg.
Receives: Drug: Filgotinib; Drug: Placebo to Match Filgotinib
Filgotinib 100 mg (LTE)ExperimentalBefore study-wide unblinding, participants will receive filgotinib 100 mg + PTM filgotinib 200 mg. After study-wide unblinding, participants will receive filgotinib 100 mg.
Receives: Drug: Filgotinib; Drug: Placebo to Match Filgotinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Week 16

Secondary outcomes (20)

  1. 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.

    Measured: Up to Week 12

  2. 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.

    Measured: Up to Week 16

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

    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.

    Measured: Week 16

  4. 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.

    Measured: Up to Week 16

  5. 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).

    Measured: Baseline and up to Week 16

  6. Proportion of Participants Who Achieve a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 50% Improvement Response

    BASDAI consists of 6 items asking participants to report their fatigue, spinal pain, peripheral arthritis, enthesitis, intensity, and duration of morning stiffness during the past week on a 0 to 10 numeric rating scale. The total score ranges 0-10; scores of 4 or greater suggest suboptimal control of disease. BASDAI 50% improvement is achieved when a decrease in BASDAI versus baseline by at least 50%.

    Measured: Up to Week 16

  7. Change From Baseline in ASDAS

    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 hsCRP. The ASDAS has a continuous scale from 0 with no defined upper end. A lower score indicates lower disease activity.

    Measured: Baseline and up to Week 16

  8. Change From Baseline in BASDAI

    BASDAI consists of 6 items asking participants to report their fatigue, spinal pain, peripheral arthritis, enthesitis, intensity, and duration of morning stiffness during the past week on a 0 to 10 numeric rating scale. The total score ranges 0-10; scores of 4 or greater suggest suboptimal control of disease.

    Measured: Baseline and up to Week 16

  9. Change From Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI)

    The BASFI evaluates physical function in AS. The instrument consists of 10 items, rated on a 0 to 10 numeric rating scale (NRS), where 0 represents "easy" and 10 represents "impossible." Among the 10 items, 8 items evaluate basic activities of daily living (putting on socks, bending, reaching up, 2 items on getting up, standing, climbing steps, and looking over shoulder) and 2 items assess participants' ability to cope with everyday life (physically demanding activities and full day's activities). The total score ranges 0-10, and the higher the score, the higher the functional impairment.

    Measured: Baseline and up to Week 16

  10. Change From Baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI) (Linear Score)

    The BASMI combines 5 measures: lateral spinal flexion, tragus-to-wall distance, lumbar flexion (modified Schober index), maximal intermalleolar distance, and cervical rotation. The BASMI will be scored using a linear function that will quantify the mobility of the axial skeleton and allow for objective assessment of clinically significant changes in spinal movement. The total score ranges 0-10, and the higher the score, the more severe the participant's limitation on movement.

    Measured: Baseline and up to Week 16

  11. Change From Baseline in Chest Expansion

    Chest expansion will be measured during maximal inspiration and maximal forced expiration at the fourth intercostal space.

    Measured: Baseline and up to Week 16

  12. Change From Baseline in Occiput-to-wall Distance

    Occiput-to-wall distance is measured twice with the participant's heels and back rested against the wall. The chin should be at usual carrying level and the participant takes maximal effort to touch the head against the wall. The distance between the occiput and the wall is assessed and the better of the 2 assessments is to be reported.

    Measured: Baseline and up to Week 16

  13. Change From Baseline in Maastricht Ankylosing Spondylitis Enthesitis Score (MASES), in Participants With Enthesitis at Baseline

    MASES is based on enthesitis grading of 13 body sites. The MASES is the sum of all site scores and ranges from 0-13. The higher the score, the higher the presence of enthesitis.

    Measured: Baseline and up to Week 16

  14. Change From Baseline in Ankylosing Spondylitis Quality of Life (ASQoL)

    The ASQoL assesses health-related quality of life in AS participants. The questionnaire consists of 18 yes/no questions. A single point will be assigned for each "yes" response, resulting in a total score between 0 and 18, with lower scores indicating a better quality of life.

    Measured: Baseline and up to Week 16

  15. Change From Baseline in Assessment of SpondyloArthritis international Society Health Index (ASAS HI)

    The ASAS HI is a 17-item patient-reported outcome measure to assess the impact of interventions for spondyloarthritis (SpA), including axial SpA. Each item consists of a question with a binary response of either "I agree" (scored as 1) or "I do not agree" (scored as 0). The scoring is performed by summing the number of "yes" answers. The total sum of the ASAS HI ranges 0-17, with a lower score indicating a better health status.

    Measured: Baseline and up to Week 16

  16. Change From Baseline in Physical Component Summary (PCS) Score of the 36-Item Short-Form Survey (SF-36) Version 2

    The SF-36 Version 2 is a health-related survey that assesses participant's quality of life and consists of 36 questions covering 8 health domains: physical functioning, bodily pain, role limitations due to physical problems and emotional problems, general health perceptions, mental health, social functioning, vitality, and 2 component scores (Mental Component Summary (MCS) score and PCS). MCS consists of social functioning, vitality, mental health, and role-emotional. PCS consists of physical functioning, bodily pain, role-physical, and general health perceptions. Each domain will be scored by summing the individual items and transforming the scores into a 0 to 100 scale with higher scores indicating better health status or functioning.

    Measured: Baseline and up to Week 16

  17. Change From Baseline in Mental Component Summary (MCS) Score of the SF-36 Version 2

    The SF-36 Version 2 is a health-related survey that assesses participant's quality of life and consists of 36 questions covering 8 health domains: physical functioning, bodily pain, role limitations due to physical problems and emotional problems, general health perceptions, mental health, social functioning, vitality, and 2 component scores (MCS and PCS). MCS consists of social functioning, vitality, mental health, and role-emotional. PCS consists of physical functioning, bodily pain, role-physical, and general health perceptions. Each domain will be scored by summing the individual items and transforming the scores into a 0 to 100 scale with higher scores indicating better health status or functioning.

    Measured: Baseline and up to Week 16

  18. Change from Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue Scale (FACIT-Fatigue)

    The FACIT-Fatigue measures an individual's level of fatigue during their usual daily activities during the past week. It consists of 13 questions on a 5-point Likert scale, with 0 indicating "not at all" and 4 indicating "very much". Negatively stated items are reversed and the total score ranges 0-52. Low scores indicate more severe fatigue than high scores.

    Measured: Baseline and up to Week 16

  19. Change From Baseline in Work Productivity and Activity Impairment for Ankylosing Spondylitis (WPAI-AS)

    The WPAI-AS is a questionnaire developed to measure impairments in work activities in participants with AS. The questionnaire consists of 6 questions (currently employed, work time missed due to AS, work time missed due to other reasons, hours actually worked, degree AS affected productivity while working [0-10 NRS; with 0 indicating no effect and 10 indicating AS completely prevented the participant from working], and degree AS affected productivity in regular unpaid activities [0-10 NRS; with 0 indicating no effect and 10 indicating AS completely prevented the participant's daily activities]). The recall period for questions 2 through 6 is 7 days.

    Four main outcomes (expressed in percentages) can be obtained from the WPAI-AS: percentage of work time missed due to AS, percentage of impairment due to AS, percentage of overall work impairment due to AS, and percentage of activity impairment due to AS. Higher numbers indicate greater impairment and less productivity.

    Measured: Baseline and up to Week 16

  20. Change From Baseline in EuroQol 5 Dimensions 5 Levels (EQ-5D-5L)

    The EQ-5D-5L is a standard measure of health-related quality of life. The tool consists of the EQ-5D-5L descriptive system and the EQ visual analogue scale (VAS). The descriptive part comprises 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). Each of these 5 dimensions has 5 levels (no problem, slight problems, moderate problems, severe problems, and extreme problems). Results for each of the 5 dimensions are combined into a 5-digit number to describe the participant's health state. The VAS records the participant's health on a 0-100 mm VAS scale, with 0 indicating "the worst health you can imagine" and 100 indicating "the best health you can imagine." Higher scores of EQ VAS indicate better health.

    Measured: Baseline and up to Week 16

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Jul 2020
  2. Study startDec 2020 (estimated)
  3. Primary completionJan 2023 (estimated)
  4. Study completionSep 2024 (estimated)

Why it stopped: Development program terminated

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04483687
Sponsor's protocol ID
GS-US-433-5305
Other IDs
2019-004298-24, 2019
Acronym
SEALION1-IR
Status last verified
Jan 2021
First submitted
20 Jul 2020
Last updated
11 Jan 2021
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Filgotinib in people with Ankylosing Spondylitis, run by Gilead Sciences.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 11 Jan 2021. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Proportion of Participants Who Achieve an Assessment of SpondyloArthritis international Society 40% Improvement (ASAS40) Response at Week 16 (time frame: Week 16). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04483687.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jan 2021.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in