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

A Randomized, Double-blind, Placebo-controlled Phase 2 Study to Evaluate the Testicular Safety of Filgotinib in Adult Males With Moderately to Severely Active Inflammatory Bowel Disease

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.

Study Overview

• Status: Terminated
• Conditions: Inflammatory Bowel Disease
• Intervention / Treatment: Drug: Filgotinib; Drug: Placebo; Drug: Standard of Care

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).

• Study Type: Interventional
• Enrollment (Actual): 139
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Monash Medical Centre
• Austria
  • Vienna, Austria, 1090
    • AKH Wien - Universitatsklinik fur Innere Medizin III
• Germany
  • Hannover, Germany, 30625
    • Medizinische Hochschule Hannover
• India
  • Ahmedabad, India, 380052
    • Kaizen Hospital
  • Bīkaner, India, 334001
    • SP Medical college & AG Hospitals
  • Dehli, India, 110026
    • Maharaja Agrasen Hospital
  • Hyderabad, India, 500082
    • Nizam's Institute of Medical Sciences
  • Jaipur, India, 302001
    • SR Kalla Memorial Gastro and General Hospital
  • Jaipur, India, 302004
    • SMS Medical College and Hospital
  • Kolhapur, India, 416006
    • Om Sai Onco Surgery Center
  • Kolkata, India, 700020
    • Institute of Post Graduate Medical Education and Research (IPGMER)
  • Kota, India, 324005
    • Radha Krishna Critical Care & General Hospital
  • Ludhiana, India, 141001
    • Dayanand Medical College & Hospital
  • Nagpur, India, 440008
    • Rahate Surgical Hospital
  • Nagpur, India, 440012
    • Crescent Hospital And Heart Centre
  • New Delhi, India, 110029
    • All India Institute of Medical Sciences
  • New Delhi, India, 110060
    • Sir Ganga Ram Hospital
  • New Delhi, India, 110062
    • Batra Hospital and Medical Research Center
  • Rajkot, India, 360005
    • Shri Griraj Multispeciality Hospital
  • Secunderabad, India, 500003
    • Gandhi Hospital
  • Secunderabad, India, 50003
    • Institute of Gastroenterology & Liver Disease, Sunshine Hospitals
  • Surat, India, 395009
    • BAPS Pramukh Swami Hospital
  • Vadodara, India, 390007
    • Sterling Hospital
  • Varanasi, India, 221005
    • Samvedna Hospital
  • Gujarat
    • Surat, Gujarat, India, 395002
      • Surat Institute of Digestive Sciences
  • Mumbai
    • Parel, Mumbai, India, 400012
      • Seth GS medical college and KEM Hospital
• New Zealand
  • Newtown, New Zealand, 6021
    • Wellington Hospital
• Poland
  • Bydgoszcz, Poland, 85-079
    • Osrodek Badan Klinicznych Cinsante S.C Ewa Galczak-Nowak
  • Kraków, Poland, 31-501
    • Krakowskie Centrum Medyczne
  • Sopot, Poland, 81-756
    • Endoskopia Sp.z o.o
  • Warsaw, Poland, 00-332
    • Bodyclinic Alicja Pasnik
  • Łódź, Poland, 90-302
    • Santa Familia, Centrum Badan Profilaktyki i Leczenia
• Romania
  • Timisoara, Romania, 300594
    • S.C. Policlinica Dr. Citu S.R.L - Gastroenterologie
• Russian Federation
  • Moscow, Russian Federation, 105554
    • Olla-Med, Llc
  • Penza, Russian Federation, 440026
    • State Budgetary Healthcare Institution, Pensa Regional Clinical Hospital n.a N.N Burdenko
  • Rostov-on-Don, Russian Federation, 344022
    • State Budgetary Educational Institution of Higher Professional Education "Rostov State Medical University" of the Ministry of Health of Russian Fedn.
  • Saint Petersburg, Russian Federation, 196247
    • Saint Petersburg State Budgetary Healthcare Institution "City Hospital # 26"
• Ukraine
  • Kharkiv, Ukraine, 61137
    • Municipal Health Care Institution "Regional Hospital of War Veterans", Therapeutic Department No. 1
  • Kiev, Ukraine, 01030
    • Kyiv City Clinical Hospital #18, Proctology Department
  • Vinnitsa, Ukraine, 21018
    • Vinnytsia Regional Clinical Hospital of War Veterans, Therapeutics Department No. 2
  • Vinnitsya, Ukraine, 21018
    • Vinnytsia Regional Clinical Hospital named after M.I. Pirogov, Gastroenterology Department
  • Vinnitsya, Ukraine, 21029
    • Medical Center LLC "Health Clinic", Medical Clinical Investigational Center
  • Vinnytsya, Ukraine, 21018
    • Vinnytsia Regional Clinical Hospital of War Veterans, Therapeutics Department No.1
  • Zaporizhzhya, Ukraine, 69096
    • Municupal Institution "Zaporizhzhia City Multidisciplinary Clinic #9" Gastrointestinal Surgery Department,
  • Zaporizhzhya, Ukraine, 69600
    • Municipal Non-profit Enterprise "Zaporizhzhia Regional Clinical Hospital" of Zaporizhzhia Regional Council,
• United Kingdom
  • Cambridge, United Kingdom, CB2 0QQ
    • Cambridge University Hospitals NHS Foundation Trust
• United States
  • California
    • San Diego, California, United States, 92134
      • Naval Medical Center San Diego
  • Florida
    • Lakewood Ranch, Florida, United States, 34211
      • Florida Research Institute
    • Miami, Florida, United States, 33136
      • University of Miami Crohn's and Colitis Center
  • Georgia
    • Norcross, Georgia, United States, 30093
      • One Health Research Clinic, Inc
  • Louisiana
    • Monroe, Louisiana, United States, 71201
      • Delta Research Partners
  • Michigan
    • Chesterfield, Michigan, United States, 48047
      • Clinical Research Institute of Michigan, LLC
  • Ohio
    • Mentor, Ohio, United States, 44060
      • Great Lakes Gastroenterology Research, LLC
  • Tennessee
    • Germantown, Tennessee, United States, 38138
      • Gastro One
  • Texas
    • Arlington, Texas, United States, 76012
      • Texas Clinical Research Institute
    • Southlake, Texas, United States, 76092
      • Texas Digestive Disease Consultants

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 17 years to 61 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: Filgotinib; 200 mg tablet administered orally once daily; 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.
Placebo Comparator: 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.	Drug: Placebo; Placebo to match filgotinib tablet administered orally once daily; 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.

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 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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Ejaculate Volume at Week 13	The normal range for ejaculate volume is ≥1.5 mL.	Baseline, Week 13
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
Percentage of Participants With a ≥ 50% Decrease From Baseline in Sperm Concentration at 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.	Baseline to Week 26
Change From Baseline in Sperm Total Motility at 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%.	Baseline, Week 26
Change From Baseline in Total Sperm Count at Week 13	The normal range for total sperm count is ≥ 39 million sperm cells/ejaculate.	Baseline, Week 13
Change From Baseline in Total Sperm Count at 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.	Baseline, Week 26
Change From Baseline in Sperm Concentration at Week 13	The normal range for sperm concentration is ≥15 million sperm cells/mL.	Baseline, Week 13
Change From Baseline in Sperm Concentration at 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.	Baseline, Week 26
Change From Baseline in Ejaculate Volume at 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.	Baseline, Week 26
Change From Baseline in Percent Normal Sperm Morphology at 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.	Baseline, Week 26

Collaborators and Investigators

• Sponsor: Galapagos NV
• Collaborators: Gilead Sciences
• Investigators: Study Director: Galapagos Study Director, Galapagos NV

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): July 11, 2017
• Primary Completion (Actual): November 20, 2020
• Study Completion (Actual): October 24, 2023

Study Registration Dates

• First Submitted: June 26, 2017
• First Submitted That Met QC Criteria: June 26, 2017
• First Posted (Actual): June 28, 2017

Study Record Updates

• Last Update Posted (Actual): October 9, 2024
• Last Update Submitted That Met QC Criteria: October 8, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Inflammatory Bowel Diseases; Intestinal Diseases
• Other Study ID Numbers: GS-US-418-4279; 2017-000402-38 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No