Study to Evaluate the Effect of Filgotinib on Semen Parameters in Adult Males With Active Rheumatoid Arthritis, Psoriatic Arthritis, Ankylosing Spondylitis, or Non-radiographic Axial Spondyloarthritis

Study Overview
=================
Brief Summary
-----------------
The primary objective of this study is to evaluate the effect of filgotinib on semen parameters in adult males with active rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, or non-radiographic axial spondyloarthritis. Results of this study may be pooled with the results of a separate study being conducted in participants with inflammatory bowel disease (Protocol GS-US-418-4279; NCT03201445) with the same objective.

Official Title
-----------------
A Randomized, Double-blind, Placebo-controlled Phase 2 Study to Evaluate the Effect of Filgotinib on Semen Parameters in Adult Males With Active Rheumatoid Arthritis, Psoriatic Arthritis, Ankylosing Spondylitis or Non-radiographic Axial Spondyloarthritis

Conditions
-----------------
Psoriatic Arthritis, Rheumatoid Arthritis, Ankylosing Spondylitis, Non-Radiographical Axial Spondyloarthritis

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


Participation Criteria
=================
Eligibility Criteria
-----------------
Key Inclusion Criteria: Diagnosis of active rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis or, non-radiographic axial spondyloarthritis for at least 12 weeks prior to screening, meeting the corresponding specific disease classification criteria as specified in the protocol Key Exclusion Criteria: Previously documented problems with male reproductive health Prior diagnosis of male infertility Use of any prohibited concomitant medication as outlined by protocol Note: Other protocol-defined Inclusion/Exclusion criteria may apply.

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

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

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 200 milligrams (mg) tablet, orally, once daily up to Week 13 in the double-blind (DB) phase. At Week 13, participants who were arthritis responders, were unblinded and received open-label (OL) treatment filgotinib 200 mg, tablet, orally, once daily up to approximately 143 weeks (until Week 156) in the extension (EXT) phase and participants who were arthritis nonresponders discontinued blinded study drug and started standard of care (SOC) treatment in the EXT phase. Participants on DB treatment or OL filgotinib who entered the monitoring phase (if their sperm parameters met ≥50% decrease threshold in pre-specified semen parameters) discontinued the study drug and started SOC for up to 52 weeks. | Drug: Filgotinib<br>* 200-mg tablet administered orally once daily<br>* Other names: Jyseleca®;Drug: Standard of Care<br>* Locally approved treatment, accepted by medical experts as a proper treatment for rheumatic conditions, prescribed according to best clinical practice, with no known testicular toxicity.<br>|
| Placebo Comparator: Placebo<br>Participants received placebo (matched to filgotinib) tablet, orally, once daily up to Week 13 in the DB phase. At Week 13, participants were unblinded and started SOC treatment in the EXT phase for up to approximately 143 weeks (until Week 156). Participants who entered the monitoring phase (if their sperm parameters met ≥50% decrease threshold in pre-specified semen parameters) continued on SOC treatment. | 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 rheumatic conditions, prescribed according to best clinical practice, with no known testicular toxicity.<br>|

What is the study measuring?
-----------------
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 sperms/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 | Arthritis responder: For rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), and non-radiographic axial spondyloarthritis (nrAxSpA), a participant with an improvement in the Physician's Global Assessment of Disease Activity (PhGADA) of at least 20% compared with baseline (Day 1) at the specified assessment time. Arthritis nonresponder: For RA, PsA, AS, or nrAxSpA, a participant who did not fulfill the definition of arthritis responder at the specified assessment timepoint. PhGADA: Physician measured the participant's disease severity on a visual analogue scale (VAS) ranged from 0 (no disease)-100 (worst disease) millimeters (mm). Baseline value for sperm/semen parameters was the mean of 2 evaluable semen collections at the screening visit. The normal range for sperm concentration is ≥15 million sperms/mL. Percentage change = ([mean at Week 26 - baseline] / baseline) × 100; value at Week 26 was the mean of 2 evaluable samples collected at Week 26. | 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 | Arthritis responder: For RA, PsA, AS, and nrAxSpA, a participant with an improvement in the PhGADA of at least 20% compared with baseline (Day 1) at the specified assessment time. Arthritis nonresponder: For RA, PsA, AS, or nrAxSpA, a participant who did not fulfill the definition of arthritis responder at the specified assessment timepoint. PhGADA: Physician measured the participant's disease severity on a VAS ranged from 0 (no disease)-100 (worst disease) mm. 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 sperms/ejaculate. | Baseline, Week 13 | 
| Change From Baseline in Total Sperm Count at Week 26 | Arthritis responder: For RA, PsA, AS, and nrAxSpA, a participant with an improvement in the PhGADA of at least 20% compared with baseline (Day 1) at the specified assessment time. Arthritis nonresponder: For RA, PsA, AS, or nrAxSpA, a participant who did not fulfill the definition of arthritis responder at the specified assessment timepoint. PhGADA: Physician measured the participant's disease severity on a VAS ranged from 0 (no disease)-100 (worst disease) mm. The normal range for total sperm count is ≥ 39 million sperms/ejaculate. | Baseline, Week 26 | 
| Change From Baseline in Sperm Concentration at Week 13 | The normal range for sperm concentration is ≥15 million sperms/mL. | Baseline, Week 13 | 
| Change From Baseline in Sperm Concentration at Week 26 | Arthritis responder: For RA, PsA, AS, and nrAxSpA, a participant with an improvement in the PhGADA of at least 20% compared with baseline (Day 1) at the specified assessment time. Arthritis nonresponder: For RA, PsA, AS, or nrAxSpA, a participant who did not fulfill the definition of arthritis responder at the specified assessment timepoint. PhGADA: Physician measured the participant's disease severity on a VAS ranged from 0 (no disease)-100 (worst disease) mm. The normal range for sperm concentration is ≥15 million sperms/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 | Arthritis responder: For RA, PsA, AS, and nrAxSpA, a participant with an improvement in the PhGADA of at least 20% compared with baseline (Day 1) at the specified assessment time. Arthritis nonresponder: For RA, PsA, AS, or nrAxSpA, a participant who did not fulfill the definition of arthritis responder at the specified assessment timepoint. PhGADA: Physician measured the participant's disease severity on a VAS ranged from 0 (no disease)-100 (worst disease) mm. 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 | Arthritis responder: For RA, PsA, AS, and nrAxSpA, a participant with an improvement in the PhGADA of at least 20% compared with baseline (Day 1) at the specified assessment time. Arthritis nonresponder: For RA, PsA, AS, or nrAxSpA, a participant who did not fulfill the definition of arthritis responder at the specified assessment timepoint. PhGADA: Physician measured the participant's disease severity on a VAS ranged from 0 (no disease)-100 (worst disease) mm. The normal range for percent normal sperm morphology is ≥30% normal sperms. | Baseline, Week 26 |