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

Phase 2

Terminated

Conditions: Inflammatory Bowel Disease

Interventions: Drug: Placebo
Drug: Filgotinib
Drug: Standard of Care

Registration Number: NCT03201445

Lead Sponsor: Galapagos NV

Brief Summary: 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: 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); 4) Monitoring Phase (MP; up to 52 weeks); and 5) Long-term Extension (LTE) Phase (after Week 26 or end of OL Filgotinib Phase for up to 195 weeks).

Recruitment & Eligibility

Status: TERMINATED

Sex: Male

Target Recruitment: 139

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

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

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 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.

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants With a ≥ 50% Decrease From Baseline in Sperm Concentration at Week 26	Baseline to 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.
Change From Baseline in Sperm Total Motility at Week 13	Baseline, Week 13	The normal range for sperm total motility is ≥40%.
Change From Baseline in Sperm Total Motility at Week 26	Baseline, 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%.
Change From Baseline in Total Sperm Count at Week 13	Baseline, Week 13	The normal range for total sperm count is ≥ 39 million sperm cells/ejaculate.
Change From Baseline in Total Sperm Count at Week 26	Baseline, 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.
Change From Baseline in Sperm Concentration at Week 13	Baseline, Week 13	The normal range for sperm concentration is ≥15 million sperm cells/mL.
Change From Baseline in Sperm Concentration at Week 26	Baseline, 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.
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	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.
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	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.

Trial Locations

Locations (56): University of Miami Crohn's and Colitis Center
🇺🇸
Miami, Florida, United States
One Health Research Clinic, Inc
🇺🇸
Norcross, Georgia, United States
Texas Clinical Research Institute
🇺🇸
Arlington, Texas, United States
Naval Medical Center San Diego
🇺🇸
San Diego, California, United States
Texas Digestive Disease Consultants
🇺🇸
Southlake, Texas, United States
Rahate Surgical Hospital
🇮🇳
Nagpur, India
SR Kalla Memorial Gastro and General Hospital
🇮🇳
Jaipur, India
Sir Ganga Ram Hospital
🇮🇳
New Delhi, India
Gastro One
🇺🇸
Germantown, Tennessee, United States
Seth GS medical college and KEM hospital
🇮🇳
Parel, Mumbai, India
SMS Medical College and Hospital
🇮🇳
Jaipur, India
Om Sai Onco Surgery Center
🇮🇳
Kolhapur, India
Medizinische Hochschule Hannover
🇩🇪
Hannover, Germany
Municipal Health Care Institution "Regional Hospital of War Veterans", Therapeutic Department No. 1
🇺🇦
Kharkiv, Ukraine
Olla-Med, Llc
🇷🇺
Moscow, Russian Federation
Surat Institute of Digestive Sciences
🇮🇳
Surat, Gujarat, India
State Budgetary Educational Institution of Higher Professional Education "Rostov State Medical University" of the Ministry of Health of Russian Fedn.
🇷🇺
Rostov-on-Don, Russian Federation
Saint Petersburg State Budgetary Healthcare Institution "City Hospital # 26"
🇷🇺
Saint Petersburg, Russian Federation
Kyiv City Clinical Hospital #18, Proctology Department
🇺🇦
Kiev, Ukraine
Vinnytsia Regional Clinical Hospital of War Veterans, Therapeutics Department No. 2
🇺🇦
Vinnitsa, Ukraine
Municupal Institution "Zaporizhzhia City Multidisciplinary Clinic #9" Gastrointestinal Surgery Department,
🇺🇦
Zaporizhzhya, Ukraine
Municipal Non-profit Enterprise "Zaporizhzhia Regional Clinical Hospital" of Zaporizhzhia Regional Council,
🇺🇦
Zaporizhzhya, Ukraine
Dayanand Medical College & Hospital
🇮🇳
Ludhiana, India
Samvedna Hospital
🇮🇳
Varanasi, India
Florida Research Institute
🇺🇸
Lakewood Ranch, Florida, United States
Clinical Research Institute of Michigan, LLC
🇺🇸
Chesterfield, Michigan, United States
Delta Research Partners
🇺🇸
Monroe, Louisiana, United States
Great Lakes Gastroenterology Research, LLC
🇺🇸
Mentor, Ohio, United States
Monash Medical Centre
🇦🇺
Clayton, Victoria, Australia
AKH Wien - Universitatsklinik fur Innere Medizin III
🇦🇹
Vienna, Austria
Kaizen Hospital
🇮🇳
Ahmedabad, India
SP Medical college & AG Hospitals
🇮🇳
Bīkaner, India
Maharaja Agrasen Hospital
🇮🇳
Dehli, India
Nizam's Institute of Medical Sciences
🇮🇳
Hyderabad, India
Institute of Post Graduate Medical Education and Research (IPGMER)
🇮🇳
Kolkata, India
Radha Krishna Critical Care & General Hospital
🇮🇳
Kota, India
Crescent Hospital and Heart Centre
🇮🇳
Nagpur, India
Batra Hospital and Medical Research Center
🇮🇳
New Delhi, India
Gandhi Hospital
🇮🇳
Secunderabad, India
All India Institute of Medical Sciences
🇮🇳
New Delhi, India
Shri Griraj Multispeciality Hospital
🇮🇳
Rajkot, India
Institute of Gastroenterology & Liver Disease, Sunshine Hospitals
🇮🇳
Secunderabad, India
Sterling Hospital
🇮🇳
Vadodara, India
BAPS Pramukh Swami Hospital
🇮🇳
Surat, India
Wellington Hospital
🇳🇿
Newtown, New Zealand
Osrodek Badan Klinicznych Cinsante S.C Ewa Galczak-Nowak
🇵🇱
Bydgoszcz, Poland
Krakowskie Centrum Medyczne
🇵🇱
Kraków, Poland
Bodyclinic Alicja Pasnik
🇵🇱
Warsaw, Poland
Endoskopia Sp.z o.o
🇵🇱
Sopot, Poland
Santa Familia, Centrum Badan Profilaktyki i Leczenia
🇵🇱
Łódź, Poland
S.C. Policlinica Dr. Citu S.R.L - Gastroenterologie
🇷🇴
Timisoara, Romania
State Budgetary Healthcare Institution, Pensa Regional Clinical Hospital n.a N.N Burdenko
🇷🇺
Penza, Russian Federation
Vinnytsia Regional Clinical Hospital named after M.I. Pirogov, Gastroenterology Department
🇺🇦
Vinnitsya, Ukraine
Medical Center LLC "Health Clinic", Medical Clinical Investigational Center
🇺🇦
Vinnitsya, Ukraine
Cambridge University Hospitals NHS Foundation Trust
🇬🇧
Cambridge, United Kingdom
Vinnytsia Regional Clinical Hospital of War Veterans, Therapeutics Department No.1
🇺🇦
Vinnytsya, Ukraine