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

Phase 2

Completed

• Conditions: Rheumatoid Arthritis; Psoriatic Arthritis; Ankylosing Spondylitis; Non-Radiographical Axial Spondyloarthritis
• Interventions: Drug: Filgotinib; Drug: Placebo; Drug: Standard of Care

• Registration Number: NCT03926195
• Lead Sponsor: Galapagos NV

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2019-04-19
• Study First Submitted QC: 2019-04-19
• Study First Posted: 2019-04-24
• Study Start: 2019-05-28
• Primary Completion: 2020-08-14
• Disposition First Submitted: 2021-07-27
• Study Completion: 2023-05-10
• Results First Submitted: 2023-05-26
• Results First Submitted QC: 2023-07-13
• Results First Posted: 2023-08-01
• Disposition First Posted: 2023-08-01
• Status Verified: 2024-04
• Last Update Submitted: 2024-04-05
• Last Update Posted: 2024-04-30

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 109

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Filgotinib	Filgotinib	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.
Filgotinib	Standard of Care	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.
Placebo	Placebo	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.
Placebo	Standard of Care	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.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With a ≥ 50% Decrease From Baseline in Sperm Concentration at Week 13	Baseline to 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.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in Sperm Total Motility at Week 13	Baseline, Week 13	The normal range for sperm total motility is ≥40%.
Percentage of Participants With a ≥ 50% Decrease From Baseline in Sperm Concentration at Week 26	Baseline to 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.
Change From Baseline in Sperm Total Motility at Week 26	Baseline, 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%.
Change From Baseline in Total Sperm Count at Week 13	Baseline, Week 13	The normal range for total sperm count is ≥ 39 million sperms/ejaculate.
Change From Baseline in Total Sperm Count at Week 26	Baseline, 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.
Change From Baseline in Sperm Concentration at Week 13	Baseline, Week 13	The normal range for sperm concentration is ≥15 million sperms/mL.
Change From Baseline in Sperm Concentration at Week 26	Baseline, 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.
Change From Baseline in Ejaculate Volume at Week 13	Baseline, Week 13	The normal range for ejaculate volume is ≥1.5 mL.
Change From Baseline in Ejaculate Volume at Week 26	Baseline, 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.
Change From Baseline in Percent Normal Sperm Morphology at Week 13	Baseline, Week 13	The normal range for percent normal sperm morphology is ≥30% normal sperms.
Change From Baseline in Percent Normal Sperm Morphology at Week 26	Baseline, 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.

Trial Locations

Locations (70)

Medical center Medconsult Pleven OOD; 🇧🇬 Pleven, Bulgaria

UMHAT Pulmed OOD; 🇧🇬 Plovdiv, Bulgaria

UMHAT Sv. Georgi, EAD; 🇧🇬 Plovdiv, Bulgaria

MHAT "Eurohospital" - Plovdiv, OOD; 🇧🇬 Plovdiv, Bulgaria

Medical Center Teodora, EOOD; 🇧🇬 Ruse, Bulgaria

Medizinski Zentar-1-Sevlievo EOOD; 🇧🇬 Sevlievo, Bulgaria

Medical Center Excelsior, OOD; 🇧🇬 Sofia, Bulgaria

DCC Alexandrovska, EOOD; 🇧🇬 Sofia, Bulgaria

UMHAT Sv. Ivan Rilski, EAD; 🇧🇬 Sofia, Bulgaria

DCC 17 - Sofia EOOD; 🇧🇬 Sofia, Bulgaria

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