A Study to Assess Efficacy and Safety of Filgotinib in Ankylosing Spondylitis

Study Overview
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Brief Summary
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This is a multicenter, Phase 2, double-blind, placebo-controlled study in subjects with active Ankylosing Spondylitis (AS). A total of approximately 100 subjects will be randomized to one of 2 treatment arms in a 1:1 ratio: oral filgotinib tablets q.d. or matching placebo q.d. Treatment duration will be 12 weeks. Each subject will stay in the study for a maximum of 20 weeks (from Screening visit to Follow-up visit).

Official Title
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A Randomized, Double-blind, Placebo-controlled, Multicenter, Phase II Study to Assess the Efficacy and Safety of Filgotinib Administered for 12 Weeks to Subjects With Active Ankylosing Spondylitis

Conditions
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Ankylosing Spondylitis

Intervention / Treatment
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* Drug: filgotinib
* Drug: Placebo Oral Tablet


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Male or female subjects who are ≥18 years of age on the day of signing informed consent. Diagnosis of moderate to severe ankylosing spondylitis with documented evidence of fulfilling the Modified New York (NY) criteria Have active ankylosing spondylitis with a BASDAI ≥4 (numeric rating scale [NRS] 0-10) and spinal pain ≥4 (0-10 NRS) (based on BASDAI question 2, see protocol) at screening and baseline. Have had a documented inadequate response to NSAIDs including cyclooxygenase-2 (COX-2) inhibitors. If using cDMARD therapy, stable dose for at lead 4 weeks prior to Baseline. If using non-drug therapies (including physical therapies), these should be kept stable during screening. Male and female subjects of childbearing potential who engage in heterosexual intercourse must agree to use highly effective methods of contraception as described in the protocol. Key Exclusion Criteria: Use of JAK inhibitors, investigational or approved, at any time, including filgotinib; Prior use of more than one TNF inhibitor, at any time. Use of oral steroids at a dose >10 mg/day of prednisone or prednisone equivalent or at a dose that hasn't been stable for at least 4 weeks prior to baseline; Any therapy by intra-articular injections (e.g. corticosteroid, hyaluronate) within 4 weeks prior to screening; Use of more than 1 NSAID or COX-2 inhibitor. Contraindication to MRI. History of known or suspected complete ankylosis of the spine. Presence of very poor functional status or unable to perform self-care. Have undergone surgical treatment for ankylosing spondylitis within the last 12 weeks prior to screening. Administration of a live or attenuated vaccine within 12 weeks prior to baseline.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: oral filgotinib tablets<br> | Drug: filgotinib<br>* one filgotinib oral tablet q.d.<br>|
| Placebo Comparator: placebo tablets<br> | Drug: Placebo Oral Tablet<br>* one placebo oral tablet q.d.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ankylosing Spondylitis disease activity score (ASDAS) in filgotinib treated subjects as compared to placebo | To evaluate the effect of filgotinib on the AS disease activity score | week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of SpondyloArthritis international Society (ASAS) in filgotinib treated subjects as compared to placebo | To evaluation the effect of filgotinib on the ASAS score in AS patients | week 12 | 
| Assessment by a trained joint assessor of 44 joints for tenderness (counting the number or tender joints - TJC) and swelling (counting the number of swollen joints - SJC) in filgotinib treated subjects as compared to placebo | To evaluate the effect of filgotinib on joint tenderness and swelling in AS patient | week 12 | 
| Assessement of the Bath Ankylosing Spondylitis Disease Activity Index in filgotinib treated subjects as compared to placebo | To assess the effect of filgotinib on BAS disease activity index in AS patients | week 12 | 
| Assessment of the Bath Ankylosing Spondylitis Functional Index in filgotinib treated subjects as compared to placebo | To assess the effect of filgotinib on BAS functional index in AS patients | week 12 | 
| Assessment of the Bath Ankylosing Spondylitis Metrology Index in filgotinib treated subjects as compared to placebo | To assess the effect of filgotinib on BAS metrology index in AS patients | week 12 | 
| Assessment Spondyloarthritis Research Consortium of Canada MRI in filgotinib treated subjects as compared to placebo | To assess the effect of filogtinib on Spondyloarthritis Research Consortium of Canada MRI in AS patients | week 12 | 
| Assessment of the Maastricht Ankylosing Spondylitis Enthesitis Score in filgotinib treated subjects as compared to placebo | To assess the effect of filgotinibe on Maastricht Ankylosing Spondylitis Enthesitis Score in AS patients | week 12 | 
| Assessment of FACIT fatigue scale in filgotinib treated subjects as compared to placebo | To assess the effect of filgotinib on FACIT fatigue scale in AS patients | week 12 | 
| Assessment of SF-36 health survey in filgotinib treated subjects as compared to placebo | To assess the effect of filgotinib on SF-36 health survey in AS patients | week 12 | 
| Assessment of Ankylosing Spondylitis Quality of Life questionnaire (ASQoL) in filgotinib treated subjects as compared to placebo | To assess the effect of filgotinib on ASQoL in AS patients | week 12 | 
| Difference between filgotinib treated subjects and placebo subjects in the number of Adverse events | To assess safety and tolerability of filgotinib in AS patients | from baseline until the final follow up visit (week 16) | 
| Difference in the number of filgotinib subjects and placebo subjects with abnormal Clinical laboratory evaluations | To assess safety and tolerability of filgotinib in AS patients | from baseline until the final follow up visit (week 16) | 
| Difference in the number of filgotinib treated subjects and placebo subjects with abnormal vital signs | To assess safety and tolerability of filgotinib in AS patients | from baseline until the final follow up visit (week 16) | 
| Difference between the number of filgotinib treated subjects and placebo subjects with abnormal physical examination | To assess safety and tolerability of filgotinib in AS patients | from baseline until the final follow up visit (week 16) | 
| Difference between the number of filgotinib treated subjects and placebo with abnormal ECG | To assess safety and tolerability of filgotinib in AS patients | At baseline, end of study visit (week 12) and final follow up visit (week 16) | 
| Difference between the number of filgotinib treated subjects and placebo with abnormal radiographic assessment | To assess safety and tolerability of filgotinib in AS patients | At baseline and end of study visit (week 12) |