Study to Evaluate the Testicular Safety of Filgotinib in Adult Males With Moderately to Severely Active Inflammatory Bowel Disease

Study Overview
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Brief Summary
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The primary objective of this study is to evaluate the testicular safety of filgotinib in adult males with moderately to severely active inflammatory bowel disease (IBD). Results of this study may be pooled with the results of a separate study being conducted in participants with rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, or non-radiographic axial spondyloarthritis (Protocol GLPG0634-CL-227; NCT03926195) with the same objective. The total planned number of participants in both studies combined will be up to approximately 250 participants.

Detailed Description
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There are 5 parts to the study: 1) Part A: Double-Blind Phase (DB Phase; Day 1 through Week 13); 2) Part B: DB Phase (after Week 13 through Week 26); 3) Open-label (OL) Filgotinib Phase (after Week 13 study visit for up to 13 weeks); Monitoring Phase (MP; up to 52 weeks); and Long-term Extension (LTE) Phase (after Week 26 or end of OL Filgotinib Phase for up to 195 weeks).

Official Title
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A Randomized, Double-blind, Placebo-controlled Phase 2 Study to Evaluate the Testicular Safety of Filgotinib in Adult Males With Moderately to Severely Active Inflammatory Bowel Disease

Conditions
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Inflammatory Bowel Disease

Intervention / Treatment
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* Drug: Filgotinib
* Drug: Placebo
* Drug: Standard of Care


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Documented diagnosis of ulcerative colitis (UC) or Crohn's Disease (CD) of at least 4 months. Endoscopic and histopathologic documentation of UC or CD. Have moderately to severely active UC or CD Key Exclusion Criteria: Previously or currently documented problems with male reproductive health Current use of sulfasalazine or its use within the 26 weeks leading up to Screening; sulfasalazine is not permitted at any point during the study Current use of corticosteroids at a dosage of > 20 mg/day of prednisone or equivalent at randomization Indeterminate colitis, ischemic colitis, fulminant colitis, isolated ulcerative proctitis, or toxic mega colon Active tuberculosis (TB) or untreated latent tuberculosis Use of concomitant prohibited medications as outlined by protocol Note: Other protocol defined Inclusion/Exclusion criteria may apply

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Male

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Filgotinib<br>Participants received filgotinib up to Week 13 in the DB phase (Part A). At Week 13, participants who were IBD responders, without meeting pre-specified sperm decrease thresholds, continued DB treatment up to Week 26 (Part B). Participants who were IBD non-responders at Week 13 or had disease worsening after Week 13 and prior to Week 26, and whose sperm parameters did not meet a prespecified decrease threshold, entered the OL Phase and received OL filgotinib for up to Week 13. At Week 26/OL Week 13, participants who were IBD responders and who had not experienced disease worsening, and whose sperm parameters did not meet a prespecified decrease threshold, continued receiving the same study drug they were responding to as part of the LTE for up to 195 weeks. Participants who met pre-specified sperm decrease threshold(s) at any postbaseline visit discontinued study drug and switched to a standard of care (SOC) regimen selected by the investigator and entered the MP for up to 52 weeks. | Drug: Filgotinib<br>* 200 mg tablet administered orally once daily<br>Drug: Standard of Care<br>* Locally approved treatment, accepted by medical experts as a proper treatment for IBD conditions, prescribed according to best clinical practice, with no known testicular toxicity.<br>|
| Placebo Comparator: Placebo<br>Participants received placebo (matched to filgotinib) up to Week 13 in the DB phase (Part A). At Week 13, participants who were IBD responders, without meeting pre-specified sperm decrease thresholds, continued DB treatment up to Week 26 (Part B). Participants who were IBD non-responders at Week 13 or had disease worsening after Week 13 and prior to Week 26, and whose sperm parameters did not meet a prespecified decrease threshold, entered the OL Phase and received OL filgotinib for up to Week 13. At Week 26/OL Week 13, participants who were IBD responders and who had not experienced disease worsening, and whose sperm parameters did not meet a prespecified decrease threshold, continued receiving the same study drug they were responding to as part of the LTE for up to 195 weeks. Participants who met pre-specified sperm decrease threshold(s) at any postbaseline visit discontinued study drug and switched to SOC regimen selected by the investigator and entered the MP for up to 52 weeks. | Drug: Placebo<br>* Placebo to match filgotinib tablet administered orally once daily<br>Drug: Standard of Care<br>* Locally approved treatment, accepted by medical experts as a proper treatment for IBD conditions, prescribed according to best clinical practice, with no known testicular toxicity.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With a ≥ 50% Decrease From Baseline in Sperm Concentration at Week 13 | Baseline for sperm/semen parameters was the mean of 2 evaluable semen samples at screening. The normal range for sperm concentration is ≥15 million sperm cells/mL. Percentage change = ([mean at Week 13 - baseline] / baseline) × 100; value at Week 13 was the mean of 2 evaluable samples collected at Week 13. | Baseline to Week 13 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With a ≥ 50% Decrease From Baseline in Sperm Concentration at Week 26 | IBD responder: For ulcerative colitis (UC), a participant who had a reduction of ≥2 in partial Mayo Clinic Score (pMCS) compared with baseline at specified time. For Crohn's disease (CD), a participant who had a reduction of ≥100 points in total Crohn's Disease Activity Index (CDAI) score compared with baseline at specified time. A participant with a baseline total CDAI score of ≥220 to ≤250 was considered an IBD responder if a CDAI score of <150 was attained at specified time. IBD nonresponder: For UC or CD, a participant who did not fulfil the definition of IBD responder at specified time. pMCS score: Sum of 3 subscores (rectal bleeding, stool frequency, and physician's global assessment) excluding endoscopic subscore; ranging from 0 (none) to 9 (severe disease). CDAI score: A weighted sum of 8 disease activity variables with scores ranging from 0 to over 600, where higher score = higher disease activity. The normal range for sperm concentration is ≥15 million sperm cells/mL. | Baseline to Week 26 | 
| Change From Baseline in Sperm Total Motility at Week 13 | The normal range for sperm total motility is ≥40%. | Baseline, Week 13 | 
| Change From Baseline in Sperm Total Motility at Week 26 | IBD responder: For UC, a participant who had a reduction of ≥ 2 in pMCS compared with baseline at specified time. For CD, a participant who had a reduction of ≥ 100 points in total CDAI score compared with baseline at specified time. A participant with a baseline total CDAI score of ≥ 220 to ≤ 250 was considered an IBD responder if a CDAI score of <150 was attained at specified time. IBD nonresponder: For UC or CD, a participant who did not fulfil the definition of IBD responder at specified time. pMCS score: Sum of 3 subscores (rectal bleeding, stool frequency, and physician's global assessment) excluding endoscopic subscore; ranging from 0 (none) to 9 (severe disease). CDAI score: A weighted sum of 8 disease activity variables with scores ranging from 0 to over 600, where higher score = higher disease activity. The normal range for sperm total motility is ≥40%. | Baseline, Week 26 | 
| Change From Baseline in Total Sperm Count at Week 13 | The normal range for total sperm count is ≥ 39 million sperm cells/ejaculate. | Baseline, Week 13 | 
| Change From Baseline in Total Sperm Count at Week 26 | IBD responder: For UC, a participant who had a reduction of ≥ 2 in pMCS compared with baseline at specified time. For CD, a participant who had a reduction of ≥ 100 points in total CDAI score compared with baseline at specified time. A participant with a baseline total CDAI score of ≥ 220 to ≤ 250 was considered an IBD responder if a CDAI score of <150 was attained at specified time. IBD nonresponder: For UC or CD, a participant who did not fulfil the definition of IBD responder at specified time. pMCS score: Sum of 3 subscores (rectal bleeding, stool frequency, and physician's global assessment) excluding endoscopic subscore; ranging from 0 (none) to 9 (severe disease). CDAI score: A weighted sum of 8 disease activity variables with scores ranging from 0 to over 600, where higher score = higher disease activity. The normal range for total sperm count is ≥ 39 million sperm cells/ejaculate. | Baseline, Week 26 | 
| Change From Baseline in Sperm Concentration at Week 13 | The normal range for sperm concentration is ≥15 million sperm cells/mL. | Baseline, Week 13 | 
| Change From Baseline in Sperm Concentration at Week 26 | IBD responder: For UC, a participant who had a reduction of ≥ 2 in pMCS compared with baseline at specified time. For CD, a participant who had a reduction of ≥ 100 points in total CDAI score compared with baseline at specified time. A participant with a baseline total CDAI score of ≥ 220 to ≤ 250 was considered an IBD responder if a CDAI score of <150 was attained at specified time. IBD nonresponder: For UC or CD, a participant who did not fulfil the definition of IBD responder at specified time. pMCS score: Sum of 3 subscores (rectal bleeding, stool frequency, and physician's global assessment) excluding endoscopic subscore; ranging from 0 (none) to 9 (severe disease). CDAI score: A weighted sum of 8 disease activity variables with scores ranging from 0 to over 600, where higher score = higher disease activity. The normal range for sperm concentration is ≥15 million sperm cells/mL. | Baseline, Week 26 | 
| Change From Baseline in Ejaculate Volume at Week 13 | The normal range for ejaculate volume is ≥1.5 mL. | Baseline, Week 13 | 
| Change From Baseline in Ejaculate Volume at Week 26 | IBD responder: For UC, a participant who had a reduction of ≥ 2 in pMCS compared with baseline at specified time. For CD, a participant who had a reduction of ≥ 100 points in total CDAI score compared with baseline at specified time. A participant with a baseline total CDAI score of ≥ 220 to ≤ 250 was considered an IBD responder if a CDAI score of <150 was attained at specified time. IBD nonresponder: For UC or CD, a participant who did not fulfil the definition of IBD responder at specified time. pMCS score: Sum of 3 subscores (rectal bleeding, stool frequency, and physician's global assessment) excluding endoscopic subscore; ranging from 0 (none) to 9 (severe disease). CDAI score: A weighted sum of 8 disease activity variables with scores ranging from 0 to over 600, where higher score = higher disease activity. The normal range for ejaculate volume is ≥1.5 mL. | Baseline, Week 26 | 
| Change From Baseline in Percent Normal Sperm Morphology at Week 13 | The normal range for percent normal sperm morphology is ≥30% normal sperms. | Baseline, Week 13 | 
| Change From Baseline in Percent Normal Sperm Morphology at Week 26 | IBD responder: For UC, a participant who had a reduction of ≥ 2 in pMCS compared with baseline at specified time. For CD, a participant who had a reduction of ≥ 100 points in total CDAI score compared with baseline at specified time. A participant with a baseline total CDAI score of ≥ 220 to ≤ 250 was considered an IBD responder if a CDAI score of <150 was attained at specified time. IBD nonresponder: For UC or CD, a participant who did not fulfil the definition of IBD responder at specified time. pMCS score: Sum of 3 subscores (rectal bleeding, stool frequency, and physician's global assessment) excluding endoscopic subscore; ranging from 0 (none) to 9 (severe disease). CDAI score: A weighted sum of 8 disease activity variables with scores ranging from 0 to over 600, where higher score = higher disease activity. The normal range for percent normal sperm morphology is ≥30% normal sperms. | Baseline, Week 26 |