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

NCT ID: NCT03201445

Last Updated: 2024-10-09

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE2

Total Enrollment

139 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-07-11

Study Completion Date

2023-10-24

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); 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).

Conditions

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Inflammatory Bowel Disease

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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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.

Group Type EXPERIMENTAL

Filgotinib

Intervention Type DRUG

200 mg tablet administered orally once daily

Standard of Care

Intervention Type 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.

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.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Placebo to match filgotinib tablet administered orally once daily

Standard of Care

Intervention Type 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.

Interventions

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Filgotinib

200 mg tablet administered orally once daily

Intervention Type DRUG

Placebo

Placebo to match filgotinib tablet administered orally once daily

Intervention Type DRUG

Standard of Care

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.

Intervention Type DRUG

Eligibility Criteria

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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

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
Minimum Eligible Age

21 Years

Maximum Eligible Age

65 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

No

Sponsors

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Gilead Sciences

INDUSTRY

Sponsor Role collaborator

Galapagos NV

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Galapagos Study Director

Role: STUDY_DIRECTOR

Galapagos NV

Locations

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Naval Medical Center San Diego

San Diego, California, United States

Site Status

Florida Research Institute

Lakewood Rch, Florida, United States

Site Status

University of Miami Crohn's and Colitis Center

Miami, Florida, United States

Site Status

One Health Research Clinic, Inc

Norcross, Georgia, United States

Site Status

Delta Research Partners

Monroe, Louisiana, United States

Site Status

Clinical Research Institute of Michigan, LLC

Chesterfield, Michigan, United States

Site Status

Great Lakes Gastroenterology Research, LLC

Mentor, Ohio, United States

Site Status

Gastro One

Germantown, Tennessee, United States

Site Status

Texas Clinical Research Institute

Arlington, Texas, United States

Site Status

Texas Digestive Disease Consultants

Southlake, Texas, United States

Site Status

Monash Medical Centre

Clayton, Victoria, Australia

Site Status

AKH Wien - Universitatsklinik fur Innere Medizin III

Vienna, , Austria

Site Status

Medizinische Hochschule Hannover

Hanover, , Germany

Site Status

Surat Institute of Digestive Sciences

Surat, Gujarat, India

Site Status

Seth GS medical college and KEM hospital

Pārel, Mumbai, India

Site Status

Kaizen Hospital

Ahmedabad, , India

Site Status

SP Medical college & AG Hospitals

Bīkaner, , India

Site Status

Maharaja Agrasen Hospital

Dehli, , India

Site Status

Nizam's Institute of Medical Sciences

Hyderabad, , India

Site Status

SR Kalla Memorial Gastro and General Hospital

Jaipur, , India

Site Status

SMS Medical College and Hospital

Jaipur, , India

Site Status

Om Sai Onco Surgery Center

Kolhāpur, , India

Site Status

Institute of Post Graduate Medical Education and Research (IPGMER)

Kolkata, , India

Site Status

Radha Krishna Critical Care & General Hospital

Kota, , India

Site Status

Dayanand Medical College & Hospital

Ludhiana, , India

Site Status

Rahate Surgical Hospital

Nagpur, , India

Site Status

Crescent Hospital and Heart Centre

Nagpur, , India

Site Status

All India Institute of Medical Sciences

New Delhi, , India

Site Status

Sir Ganga Ram Hospital

New Delhi, , India

Site Status

Batra Hospital and Medical Research Center

New Delhi, , India

Site Status

Shri Griraj Multispeciality Hospital

Rajkot, , India

Site Status

Gandhi Hospital

Secunderabad, , India

Site Status

Institute of Gastroenterology & Liver Disease, Sunshine Hospitals

Secunderabad, , India

Site Status

BAPS Pramukh Swami Hospital

Surat, , India

Site Status

Sterling Hospital

Vadodara, , India

Site Status

Samvedna Hospital

Varanasi, , India

Site Status

Wellington Hospital

Newtown, , New Zealand

Site Status

Osrodek Badan Klinicznych Cinsante S.C Ewa Galczak-Nowak

Bydgoszcz, , Poland

Site Status

Krakowskie Centrum Medyczne

Krakow, , Poland

Site Status

Santa Familia, Centrum Badan Profilaktyki i Leczenia

Lodz, , Poland

Site Status

Endoskopia Sp.z o.o

Sopot, , Poland

Site Status

Bodyclinic Alicja Pasnik

Warsaw, , Poland

Site Status

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

Timișoara, , Romania

Site Status

Olla-Med, Llc

Moscow, , Russia

Site Status

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

Penza, , Russia

Site Status

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

Rostov-on-Don, , Russia

Site Status

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

Saint Petersburg, , Russia

Site Status

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

Kharkiv, , Ukraine

Site Status

Kyiv City Clinical Hospital #18, Proctology Department

Kiev, , Ukraine

Site Status

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

Vinnitsa, , Ukraine

Site Status

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

Vinnitsya, , Ukraine

Site Status

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

Vinnitsya, , Ukraine

Site Status

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

Vinnytsia, , Ukraine

Site Status

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

Zaporizhzhya, , Ukraine

Site Status

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

Zaporizhzhya, , Ukraine

Site Status

Cambridge University Hospitals NHS Foundation Trust

Cambridge, , United Kingdom

Site Status

Countries

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United States Australia Austria Germany India New Zealand Poland Romania Russia Ukraine United Kingdom

References

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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.

Reference Type DERIVED
PMID: 37137672 (View on PubMed)

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.

Reference Type DERIVED
PMID: 35614292 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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2017-000402-38

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GS-US-418-4279

Identifier Type: -

Identifier Source: org_study_id

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