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

NCT03201445 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: GS-US-418-42792017-000402-38
• Study Type: interventional
• Target: 139
• Locations: 10 countries
• Sites: 55

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.

Conditions

Inflammatory Bowel Disease

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (11)

• Percentage of Participants With a ≥ 50% Decrease From Baseline in Sperm Concentration at Week 26

  Baseline to Week 26

• Change From Baseline in Sperm Total Motility at Week 13

  Baseline, Week 13

• Change From Baseline in Sperm Total Motility at Week 26

  Baseline, Week 26

• Change From Baseline in Total Sperm Count at Week 13

  Baseline, Week 13

• Change From Baseline in Total Sperm Count at Week 26

  Baseline, Week 26

Study Arms (2)

Filgotinib

EXPERIMENTAL

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; Drug: Standard of Care

Placebo

PLACEBO COMPARATOR

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; Drug: Standard of Care

Interventions

Filgotinib DRUG

200 mg tablet administered orally once daily

Filgotinib

Placebo DRUG

Placebo to match filgotinib tablet administered orally once daily

Placebo

Standard of Care DRUG

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.

Filgotinib; Placebo

Eligibility Criteria

• Age: 21 Years - 65 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Galapagos NV: lead
• Gilead Sciences: collaborator

Study Sites (56)

Naval Medical Center San Diego

San Diego, California, 92134, United States

Location

Florida Research Institute

Lakewood Rch, Florida, 34211, United States

Location

University of Miami Crohn's and Colitis Center

Miami, Florida, 33136, United States

Location

One Health Research Clinic, Inc

Norcross, Georgia, 30093, United States

Location

Delta Research Partners

Monroe, Louisiana, 71201, United States

Location

Clinical Research Institute of Michigan, LLC

Chesterfield, Michigan, 48047, United States

Location

Great Lakes Gastroenterology Research, LLC

Mentor, Ohio, 44060, United States

Location

Gastro One

Germantown, Tennessee, 38138, United States

Location

Texas Clinical Research Institute

Arlington, Texas, 76012, United States

Location

Texas Digestive Disease Consultants

Southlake, Texas, 76092, United States

Location

Monash Medical Centre

Clayton, Victoria, 3168, Australia

Location

AKH Wien - Universitatsklinik fur Innere Medizin III

Vienna, 1090, Austria

Location

Medizinische Hochschule Hannover

Hanover, 30625, Germany

Location

Surat Institute of Digestive Sciences

Surat, Gujarat, 395002, India

Location

Seth GS medical college and KEM hospital

Pārel, Mumbai, 400012, India

Location

Kaizen Hospital

Ahmedabad, 380052, India

Location

SP Medical college & AG Hospitals

Bīkaner, 334001, India

Location

Maharaja Agrasen Hospital

Dehli, 110026, India

Location

Nizam's Institute of Medical Sciences

Hyderabad, 500082, India

Location

SR Kalla Memorial Gastro and General Hospital

Jaipur, 302001, India

Location

SMS Medical College and Hospital

Jaipur, 302004, India

Location

Om Sai Onco Surgery Center

Kolhāpur, 416006, India

Location

Institute of Post Graduate Medical Education and Research (IPGMER)

Kolkata, 700020, India

Location

Radha Krishna Critical Care & General Hospital

Kota, 324005, India

Location

Dayanand Medical College & Hospital

Ludhiana, 141001, India

Location

Rahate Surgical Hospital

Nagpur, 440008, India

Location

Crescent Hospital and Heart Centre

Nagpur, 440012, India

Location

All India Institute of Medical Sciences

New Delhi, 110029, India

Location

Sir Ganga Ram Hospital

New Delhi, 110060, India

Location

Batra Hospital and Medical Research Center

New Delhi, 110062, India

Location

Shri Griraj Multispeciality Hospital

Rajkot, 360005, India

Location

Gandhi Hospital

Secunderabad, 500003, India

Location

Institute of Gastroenterology & Liver Disease, Sunshine Hospitals

Secunderabad, 50003, India

Location

BAPS Pramukh Swami Hospital

Surat, 395009, India

Location

Sterling Hospital

Vadodara, 390007, India

Location

Samvedna Hospital

Varanasi, 221005, India

Location

Wellington Hospital

Newtown, 6021, New Zealand

Location

Osrodek Badan Klinicznych Cinsante S.C Ewa Galczak-Nowak

Bydgoszcz, 85-079, Poland

Location

Krakowskie Centrum Medyczne

Krakow, 31-501, Poland

Location

Santa Familia, Centrum Badan Profilaktyki i Leczenia

Lodz, 90-302, Poland

Location

Endoskopia Sp.z o.o

Sopot, 81-756, Poland

Location

Bodyclinic Alicja Pasnik

Warsaw, 00-332, Poland

Location

S.C. Policlinica Dr. Citu S.R.L - Gastroenterologie

Timișoara, 300594, Romania

Location

Olla-Med, Llc

Moscow, 105554, Russia

Location

State Budgetary Healthcare Institution, Pensa Regional Clinical Hospital n.a N.N Burdenko

Penza, 440026, Russia

Location

State Budgetary Educational Institution of Higher Professional Education "Rostov State Medical University" of the Ministry of Health of Russian Fedn.

Rostov-on-Don, 344022, Russia

Location

Saint Petersburg State Budgetary Healthcare Institution "City Hospital # 26"

Saint Petersburg, 196247, Russia

Location

Municipal Health Care Institution "Regional Hospital of War Veterans", Therapeutic Department No. 1

Kharkiv, 61137, Ukraine

Location

Kyiv City Clinical Hospital #18, Proctology Department

Kiev, 01030, Ukraine

Location

Vinnytsia Regional Clinical Hospital of War Veterans, Therapeutics Department No. 2

Vinnitsa, 21018, Ukraine

Location

Vinnytsia Regional Clinical Hospital named after M.I. Pirogov, Gastroenterology Department

Vinnitsya, 21018, Ukraine

Location

Medical Center LLC "Health Clinic", Medical Clinical Investigational Center

Vinnitsya, 21029, Ukraine

Location

Vinnytsia Regional Clinical Hospital of War Veterans, Therapeutics Department No.1

Vinnytsia, 21018, Ukraine

Location

Municupal Institution "Zaporizhzhia City Multidisciplinary Clinic #9" Gastrointestinal Surgery Department,

Zaporizhzhya, 69096, Ukraine

Location

Municipal Non-profit Enterprise "Zaporizhzhia Regional Clinical Hospital" of Zaporizhzhia Regional Council,

Zaporizhzhya, 69600, Ukraine

Location

Cambridge University Hospitals NHS Foundation Trust

Cambridge, CB2 0QQ, United Kingdom

Location

Related Publications (2)

• Reinisch W, Hellstrom W, Dolhain RJEM, Sikka S, Westhovens R, Mehta R, Ritter T, Seidler U, Golovchenko O, Simanenkov V, Garmish O, Jeka S, Moravcova R, Rajendran V, Le Brun FO, Arterburn S, Watkins TR, Besuyen R, Vanderschueren D. Effects of filgotinib on semen parameters and sex hormones in male patients with inflammatory diseases: results from the phase 2, randomised, double-blind, placebo-controlled MANTA and MANTA-RAy studies. Ann Rheum Dis. 2023 Aug;82(8):1049-1058. doi: 10.1136/ard-2023-224017. Epub 2023 May 3.

  PMID: 37137672 DERIVED

• Hellstrom WJG, Dolhain RJEM, Ritter TE, Watkins TR, Arterburn SJ, Dekkers G, Gillen A, Tonussi C, Gilles L, Oortwijn A, Van Beneden K, de Vries DE, Sikka SC, Vanderschueren D, Reinisch W. MANTA and MANTA-RAy: Rationale and Design of Trials Evaluating Effects of Filgotinib on Semen Parameters in Patients with Inflammatory Diseases. Adv Ther. 2022 Jul;39(7):3403-3422. doi: 10.1007/s12325-022-02168-4. Epub 2022 May 25.

  PMID: 35614292 DERIVED

MeSH Terms

Conditions

Inflammatory Bowel Diseases

Interventions

GLPG0634; Standard of Care

Condition Hierarchy (Ancestors)

Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Limitations and Caveats

The study was terminated based on the sponsor's decision for reasons other than safety.

Results Point of Contact

• Title: Galapagos Medical Information
• Organization: Galapagos NV

medicalinfo@glpg.com

+32 15 342 900

Study Officials

• Galapagos Study Director

  Galapagos NV

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 26, 2017
• First Posted: June 28, 2017
• Study Start: July 11, 2017
• Primary Completion: November 20, 2020
• Study Completion: October 24, 2023
• Last Updated: October 9, 2024
• Results First Posted: December 6, 2023

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1); NZ (1); AU (1); RO (1); PL (5); UA (8); GB (1); US (10); RU (4); IN (23)