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TerminatedNCT03201445MANTAUpdated Oct 9, 2024Results posted

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

A Phase 2 interventional study of Filgotinib and Placebo in Inflammatory Bowel Disease, sponsored by Lakefront Biotherapeutics NV. Terminated at 56 sites in 11 countries. Open to male participants aged 21 Years to 65 Years. Per ClinicalTrials.gov, last updated 2024-10-09.

Sponsored by Lakefront Biotherapeutics NV · Phase 2, Interventional, and Treatment

Why this study was terminated
Early Termination for Reasons other than Safety
Phase
Phase 2
Study type
Interventional
Enrollment
139
Allocation
Randomized
Ages
21 Years to 65 Years
Sex
Male
01

Study 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.

Read the 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).

02

Conditions studied

  • Inflammatory Bowel Disease
03

In context

Inflammatory Bowel Diseases

1,487 studies on the registry are indexed under Inflammatory Bowel Diseases; 434 are open to participants now.

This study's enrollment of 139 is above the median of 70 across 783 interventional studies indexed under Inflammatory Bowel Diseases.

Browse Inflammatory Bowel Diseases studies →

Lead sponsor

Lakefront Biotherapeutics NV is the lead sponsor of 10 studies on the registry; 1 is open to participants now.

Of its 5 completed or terminated interventional studies of FDA-regulated products, 2 (40%) have results posted.

Browse Lakefront Biotherapeutics NV studies →

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
21 Years to 65 Years
Sexes eligible
Male
Accepts healthy volunteers
No

Eligibility criteria

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

05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Double (Participant, Investigator)
Enrollment
139 participants (actual)

Study arms

  • 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 · Drug: Standard of Care

  • 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 · Drug: Standard of Care

Interventions

  • DrugFilgotinib

    200 mg tablet administered orally once daily

  • DrugPlacebo

    Placebo to match filgotinib tablet administered orally once daily

  • DrugStandard 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.

06

What researchers measure

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.

    Time frame: Baseline to Week 13

Secondary outcomes

  1. 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.

    Time frame: Baseline to Week 26

  2. Change From Baseline in Sperm Total Motility at Week 13

    The normal range for sperm total motility is ≥40%.

    Time frame: Baseline, Week 13

  3. 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%.

    Time frame: Baseline, Week 26

  4. Change From Baseline in Total Sperm Count at Week 13

    The normal range for total sperm count is ≥ 39 million sperm cells/ejaculate.

    Time frame: Baseline, Week 13

  5. 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.

    Time frame: Baseline, Week 26

  6. Change From Baseline in Sperm Concentration at Week 13

    The normal range for sperm concentration is ≥15 million sperm cells/mL.

    Time frame: Baseline, Week 13

  7. 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.

    Time frame: Baseline, Week 26

  8. Change From Baseline in Ejaculate Volume at Week 13

    The normal range for ejaculate volume is ≥1.5 mL.

    Time frame: Baseline, Week 13

  9. 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.

    Time frame: Baseline, Week 26

  10. Change From Baseline in Percent Normal Sperm Morphology at Week 13

    The normal range for percent normal sperm morphology is ≥30% normal sperms.

    Time frame: Baseline, Week 13

  11. 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.

    Time frame: Baseline, Week 26

07

Results

Posted Dec 6, 2023
Limitations and caveats
The study was terminated based on the sponsor's decision for reasons other than safety.

Participant flow

Participants were enrolled at study sites in Australia, Austria, Germany, India, New Zealand, Poland, Romania, Russian Federation, Ukraine, United Kingdom, and United States. The first participant was screened on 11 July 2017. A total of 323 participants were screened of which 139 participants were randomized into the study.

Part A DB Phase (Through Week 13)
Participant flow — Part A DB Phase (Through Week 13)
MilestoneFilgotinibPlacebo
Started6970
Completed6867
Not completed13
Withdrew: Lost to follow-up10
Withdrew: Protocol violation01
Withdrew: Withdrawal by subject02
Part B DB Phase (Week 13 to 26)
Participant flow — Part B DB Phase (Week 13 to 26)
MilestoneFilgotinibPlacebo
Started4538
Completed4238
Not completed30
Withdrew: Adverse event10
Withdrew: Progressive disease20
OL Phase (13 Weeks)
Participant flow — OL Phase (13 Weeks)
MilestoneFilgotinibPlacebo
Started2423
Completed2220
Not completed23
Withdrew: Adverse event02
Withdrew: Withdrawal by subject21
LTE: DB Study Drug (up to Week 195)
Participant flow — LTE: DB Study Drug (up to Week 195)
MilestoneFilgotinibPlacebo
Started3834
Completed85
Not completed3029
Withdrew: Adverse event910
Withdrew: Lost to follow-up01
Withdrew: Physician decision02
Withdrew: Withdrawal by subject44
Withdrew: Pre-specified decrease in sperm parameters (switched to mp)67
Withdrew: Study terminated by sponsor115
LTE: OL Study Drug (Up to Week 195)
Participant flow — LTE: OL Study Drug (Up to Week 195)
MilestoneFilgotinibPlacebo
Started1816
Completed02
Not completed1814
Withdrew: Adverse event32
Withdrew: Physician decision12
Withdrew: Withdrawal by subject11
Withdrew: Pre-specified decrease in sperm parameters (switched to mp)53
Withdrew: Progressive disease20
Withdrew: Study terminated by sponsor66
Monitoring Phase (Up to Week 52)
Participant flow — Monitoring Phase (Up to Week 52)
MilestoneFilgotinibPlacebo
Started1521
Completed1419
Not completed12
Withdrew: Withdrawal by subject11
Withdrew: Study terminated by sponsor01

Outcome measures

PrimaryPercentage 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.

Time frame:
Baseline to Week 13
Reported as:
Number · percentage of participants
Percentage of Participants With a ≥ 50% Decrease From Baseline in Sperm Concentration at Week 13
percentage of participantsFilgotinibPlacebo
Percentage of Participants With a ≥ 50% Decrease From Baseline in Sperm Concentration at Week 131.59.0
Statistical analysis
  • Filgotinib vs Placebo · Difference in percentage: -7.8 · 95% CI -16.3 to 0.7Difference in percentage and 95% confidence interval (CI) was based on a stratified Mantel-Haenszel test.
SecondaryPercentage 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.

Time frame:
Baseline to Week 26
Reported as:
Number · percentage of participants
Percentage of Participants With a ≥ 50% Decrease From Baseline in Sperm Concentration at Week 26
percentage of participantsFilgotinib/DB Filgotinib (Responder)Filgotinib/OL Filgotinib (Nonresponder)Placebo/DB Placebo (Responder)Placebo/OL Filgotinib (Nonresponder)
Percentage of Participants With a ≥ 50% Decrease From Baseline in Sperm Concentration at Week 265.007.911.8
SecondaryChange From Baseline in Sperm Total Motility at Week 13

The normal range for sperm total motility is ≥40%.

Time frame:
Baseline, Week 13
Reported as:
Median · percentage of motile sperms
Change From Baseline in Sperm Total Motility at Week 13
percentage of motile spermsFilgotinibPlacebo
Change From Baseline in Sperm Total Motility at Week 13-0.3 (-1.6 to 1.7)0.4 (-1.3 to 1.5)
Statistical analysis
  • Filgotinib vs Placebo · Median difference (final values): -0.2 · 95% CI -2.1 to 1.8Difference in Medians and 95% CI for change from baseline at Week 13 was based on quantile regression.
SecondaryChange 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%.

Time frame:
Baseline, Week 26
Reported as:
Median · percentage of motile sperms
Change From Baseline in Sperm Total Motility at Week 26
percentage of motile spermsFilgotinib/DB Filgotinib (Responder)Filgotinib/OL Filgotinib (Nonresponder)Placebo/DB Placebo (Responder)Placebo/OL Filgotinib (Nonresponder)
Change From Baseline in Sperm Total Motility at Week 26-2.3 (-4.7 to -0.3)-1.5 (-5.8 to 2.6)0.0 (-3.4 to 2.4)0.8 (-7.3 to 5.8)
SecondaryChange From Baseline in Total Sperm Count at Week 13

The normal range for total sperm count is ≥ 39 million sperm cells/ejaculate.

Time frame:
Baseline, Week 13
Reported as:
Median · million sperm cells/ejaculate
Change From Baseline in Total Sperm Count at Week 13
million sperm cells/ejaculateFilgotinibPlacebo
Change From Baseline in Total Sperm Count at Week 13-11.6 (-19.8 to 9.7)-9.5 (-23.8 to 0.6)
Statistical analysis
  • Filgotinib vs Placebo · Median difference (final values): 5.7 · 95% CI -13.4 to 24.7Difference in medians and 95% CI for change from baseline at Week 13 was based on quantile regression.
SecondaryChange 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.

Time frame:
Baseline, Week 26
Reported as:
Median · million sperm cells/ejaculate
Change From Baseline in Total Sperm Count at Week 26
million sperm cells/ejaculateFilgotinib/DB Filgotinib (Responder)Filgotinib/OL Filgotinib (Nonresponder)Placebo/DB Placebo (Responder)Placebo/OL Filgotinib (Nonresponder)
Change From Baseline in Total Sperm Count at Week 262.0 (-19.6 to 17.2)-4.6 (-42.3 to 18.3)-4.1 (-39.8 to 15.9)12.7 (-61.4 to 40.8)
SecondaryChange From Baseline in Sperm Concentration at Week 13

The normal range for sperm concentration is ≥15 million sperm cells/mL.

Time frame:
Baseline, Week 13
Reported as:
Median · million sperm cells/mL
Change From Baseline in Sperm Concentration at Week 13
million sperm cells/mLFilgotinibPlacebo
Change From Baseline in Sperm Concentration at Week 131.0 (-2.2 to 3.9)0.7 (-2.7 to 1.7)
Statistical analysis
  • Filgotinib vs Placebo · Median difference (final values): 1.0 · 95% CI -2.8 to 4.9Difference in Medians and 95% CI for change from baseline at Week 13 was based on quantile regression.
SecondaryChange 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.

Time frame:
Baseline, Week 26
Reported as:
Median · million sperm cells/mL
Change From Baseline in Sperm Concentration at Week 26
million sperm cells/mLFilgotinib/DB Filgotinib (Responder)Filgotinib/OL Filgotinib (Nonresponder)Placebo/DB Placebo (Responder)Placebo/OL Filgotinib (Nonresponder)
Change From Baseline in Sperm Concentration at Week 261.2 (-3.2 to 10.8)-0.6 (-8.5 to 23.0)0.8 (-2.4 to 5.3)-3.7 (-11.1 to 15.7)
SecondaryChange From Baseline in Ejaculate Volume at Week 13

The normal range for ejaculate volume is ≥1.5 mL.

Time frame:
Baseline, Week 13
Reported as:
Median · mL
Change From Baseline in Ejaculate Volume at Week 13
mLFilgotinibPlacebo
Change From Baseline in Ejaculate Volume at Week 13-0.2 (-0.3 to 0.1)-0.1 (-0.3 to 0.0)
Statistical analysis
  • Filgotinib vs Placebo · Median difference (final values): 0.1 · 95% CI -0.1 to 0.3Difference in Medians and 95% CI for change from baseline at Week 13 was based on quantile regression.
SecondaryChange 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.

Time frame:
Baseline, Week 26
Reported as:
Median · mL
Change From Baseline in Ejaculate Volume at Week 26
mLFilgotinib/DB Filgotinib (Responder)Filgotinib/OL Filgotinib (Nonresponder)Placebo/DB Placebo (Responder)Placebo/OL Filgotinib (Nonresponder)
Change From Baseline in Ejaculate Volume at Week 260.0 (-0.5 to 0.2)-0.3 (-0.8 to 0.2)-0.2 (-0.5 to 0.1)-0.1 (-0.7 to 0.4)
SecondaryChange From Baseline in Percent Normal Sperm Morphology at Week 13

The normal range for percent normal sperm morphology is ≥30% normal sperms.

Time frame:
Baseline, Week 13
Reported as:
Median · percentage of normal sperms
Change From Baseline in Percent Normal Sperm Morphology at Week 13
percentage of normal spermsFilgotinibPlacebo
Change From Baseline in Percent Normal Sperm Morphology at Week 132 (-1 to 4)1 (-1 to 2)
Statistical analysis
  • Filgotinib vs Placebo · Median difference (final values): 2 · 95% CI 0 to 4Difference in Medians and 95% CI for change from baseline at Week 13 was based on quantile regression.
SecondaryChange 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.

Time frame:
Baseline, Week 26
Reported as:
Median · percentage of normal sperms
Change From Baseline in Percent Normal Sperm Morphology at Week 26
percentage of normal spermsFilgotinib/DB Filgotinib (Responder)Filgotinib/OL Filgotinib (Nonresponder)Placebo/DB Placebo (Responder)Placebo/OL Filgotinib (Nonresponder)
Change From Baseline in Percent Normal Sperm Morphology at Week 263 (1 to 5)1 (-2 to 3)2 (-4 to 5)2 (-2 to 3)

Adverse events

Collected over From first dose up to Week 226. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Filgotinib0/92 (0%)3/92 (3.3%)47/92 (51.1%)
Placebo0/70 (0%)2/70 (2.9%)24/70 (34.3%)
Most frequent serious events
Most frequent serious events
EventFilgotinibPlacebo
Colitis ulcerativeGastrointestinal disorders1/921/70
COVID-19Infections and infestations0/921/70
Crohn's diseaseGastrointestinal disorders1/920/70
PneumoniaInfections and infestations1/920/70
Most frequent other events
Most frequent other events
EventFilgotinibPlacebo
NasopharyngitisInfections and infestations17/923/70
Colitis ulcerativeGastrointestinal disorders14/923/70
COVID-19Infections and infestations9/923/70
HeadacheNervous system disorders7/920/70
GastritisGastrointestinal disorders7/921/70
Latent tuberculosisInfections and infestations5/925/70
Abdominal painGastrointestinal disorders3/925/70
FuruncleInfections and infestations1/924/70
PyrexiaGeneral disorders5/924/70

Baseline characteristics

The Safety Analysis Set included all randomized participants who took ≥ 1 dose of double-blind study drug.

Age, Continuous
Age, Continuous(years)FilgotinibPlaceboTotal
Mean36 ± 8.534 ± 8.435 ± 8.5
Sex: Female, Male
Sex: Female, Male(Participants)FilgotinibPlaceboTotal
Female000
Male6970139
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)FilgotinibPlaceboTotal
Ethnicity — Not Hispanic or Latino6868136
Ethnicity — Hispanic or Latino112
Ethnicity — Not Permitted011
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)FilgotinibPlaceboTotal
Race — American Indian or Alaska Native202
Race — Asian373875
Race — Black or African American101
Race — White293160
Race — Not Permitted011
Sperm Concentration
Sperm Concentration(million sperm cells/milliliter (mL))FilgotinibPlaceboTotal
Mean63.4 ± 34.3461.8 ± 34.9662.6 ± 34.53
Total Sperm Count
Total Sperm Count(million sperm cells/ejaculate)FilgotinibPlaceboTotal
Mean190.6 ± 107.08171.1 ± 100.74180.8 ± 104.02
Sperm Total Motility
Sperm Total Motility(percentage of motile sperm)FilgotinibPlaceboTotal
Mean59.6 ± 11.3358.6 ± 10.9459.1 ± 11.11
Ejaculate Volume
Ejaculate Volume(mL)FilgotinibPlaceboTotal
Mean3.2 ± 1.203.0 ± 1.483.1 ± 1.35

1 further baseline measures are reported on the registry.

08

Study locations

56 sites
  • Naval Medical Center San Diego
    San Diego, California 92134, United States
  • Florida Research Institute
    Lakewood Rch, Florida 34211, United States
  • University of Miami Crohn's and Colitis Center
    Miami, Florida 33136, United States
  • One Health Research Clinic, Inc
    Norcross, Georgia 30093, United States
  • Delta Research Partners
    Monroe, Louisiana 71201, United States
  • Clinical Research Institute of Michigan, LLC
    Chesterfield, Michigan 48047, United States
  • Great Lakes Gastroenterology Research, LLC
    Mentor, Ohio 44060, United States
  • Gastro One
    Germantown, Tennessee 38138, United States
  • Texas Clinical Research Institute
    Arlington, Texas 76012, United States
  • Texas Digestive Disease Consultants
    Southlake, Texas 76092, United States
  • Monash Medical Centre
    Clayton, Victoria 3168, Australia
  • AKH Wien - Universitatsklinik fur Innere Medizin III
    Vienna, 1090, Austria
  • Medizinische Hochschule Hannover
    Hanover, 30625, Germany
  • Surat Institute of Digestive Sciences
    Surat, Gujarat 395002, India
  • Seth GS medical college and KEM hospital
    Pārel, Mumbai 400012, India
  • Kaizen Hospital
    Ahmedabad, 380052, India
  • SP Medical college & AG Hospitals
    Bīkaner, 334001, India
  • Maharaja Agrasen Hospital
    Dehli, 110026, India
  • Nizam's Institute of Medical Sciences
    Hyderabad, 500082, India
  • SR Kalla Memorial Gastro and General Hospital
    Jaipur, 302001, India
  • SMS Medical College and Hospital
    Jaipur, 302004, India
  • Om Sai Onco Surgery Center
    Kolhāpur, 416006, India
  • Institute of Post Graduate Medical Education and Research (IPGMER)
    Kolkata, 700020, India
  • Radha Krishna Critical Care & General Hospital
    Kota, 324005, India
  • Dayanand Medical College & Hospital
    Ludhiana, 141001, India
  • Rahate Surgical Hospital
    Nagpur, 440008, India
  • Crescent Hospital and Heart Centre
    Nagpur, 440012, India
  • All India Institute of Medical Sciences
    New Delhi, 110029, India
  • Sir Ganga Ram Hospital
    New Delhi, 110060, India
  • Batra Hospital and Medical Research Center
    New Delhi, 110062, India
  • Shri Griraj Multispeciality Hospital
    Rajkot, 360005, India
  • Gandhi Hospital
    Secunderabad, 500003, India
  • Institute of Gastroenterology & Liver Disease, Sunshine Hospitals
    Secunderabad, 50003, India
  • BAPS Pramukh Swami Hospital
    Surat, 395009, India
  • Sterling Hospital
    Vadodara, 390007, India
  • Samvedna Hospital
    Varanasi, 221005, India
  • Wellington Hospital
    Newtown, 6021, New Zealand
  • Osrodek Badan Klinicznych Cinsante S.C Ewa Galczak-Nowak
    Bydgoszcz, 85-079, Poland
  • Krakowskie Centrum Medyczne
    Krakow, 31-501, Poland
  • Santa Familia, Centrum Badan Profilaktyki i Leczenia
    Lodz, 90-302, Poland
  • Endoskopia Sp.z o.o
    Sopot, 81-756, Poland
  • Bodyclinic Alicja Pasnik
    Warsaw, 00-332, Poland
  • S.C. Policlinica Dr. Citu S.R.L - Gastroenterologie
    Timișoara, 300594, Romania
  • Olla-Med, Llc
    Moscow, 105554, Russia
  • State Budgetary Healthcare Institution, Pensa Regional Clinical Hospital n.a N.N Burdenko
    Penza, 440026, Russia
  • 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
  • Saint Petersburg State Budgetary Healthcare Institution "City Hospital # 26"
    Saint Petersburg, 196247, Russia
  • Municipal Health Care Institution "Regional Hospital of War Veterans", Therapeutic Department No. 1
    Kharkiv, 61137, Ukraine
  • Kyiv City Clinical Hospital #18, Proctology Department
    Kiev, 01030, Ukraine
  • Vinnytsia Regional Clinical Hospital of War Veterans, Therapeutics Department No. 2
    Vinnitsa, 21018, Ukraine
  • Vinnytsia Regional Clinical Hospital named after M.I. Pirogov, Gastroenterology Department
    Vinnitsya, 21018, Ukraine
  • Medical Center LLC "Health Clinic", Medical Clinical Investigational Center
    Vinnitsya, 21029, Ukraine
  • Vinnytsia Regional Clinical Hospital of War Veterans, Therapeutics Department No.1
    Vinnytsia, 21018, Ukraine
  • Municupal Institution "Zaporizhzhia City Multidisciplinary Clinic #9" Gastrointestinal Surgery Department,
    Zaporizhzhya, 69096, Ukraine
  • Municipal Non-profit Enterprise "Zaporizhzhia Regional Clinical Hospital" of Zaporizhzhia Regional Council,
    Zaporizhzhya, 69600, Ukraine
  • Cambridge University Hospitals NHS Foundation Trust
    Cambridge, CB2 0QQ, United Kingdom
09

References and documents

Publications

  • 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. PubMed 37137672 ↗
  • 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. PubMed 35614292 ↗

Study documents

  • Study protocol · Sep 9, 2022
  • Statistical analysis plan · Jan 13, 2021

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Oct 9, 2024, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT03201445
Lead sponsor
Lakefront Biotherapeutics NV
Collaborators
Gilead Sciences
Responsible party
Sponsor
First posted
Jun 28, 2017
Start date
Jul 11, 2017
Primary completion
Nov 20, 2020
Completion
Oct 24, 2023
Results posted
Dec 6, 2023
Last update
Oct 9, 2024

Study contacts

Galapagos Study Director
study director · Lakefront Biotherapeutics NV

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is terminated, as verified in Oct 2024. You cannot join it, but the record below documents what was studied.

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Studies of the drug tested here: GLPG0634

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