NCT03201445: MANTA

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

Terminated Phase 2 Results posted Last updated 9 October 2024

What this trial tests

Phase 2 trial testing Filgotinib in Inflammatory Bowel Disease in 139 participants. Terminated before completion.

Timeline

11 July 2017

Primary endpoint
20 November 2020

24 October 2023

Quick facts

Lead sponsor	Galapagos NV
Phase	Phase 2
Status	Terminated
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	double
Primary purpose	treatment
Enrollment	139
Start date	11 July 2017
Primary completion	20 November 2020
Estimated completion	24 October 2023
Sites	56 locations across New Zealand, Russia, Ukraine, Austria, United Kingdom, Germany, Poland, Romania

Drugs / interventions tested

• Filgotinib (FILGOTINIB) — full drug profile →
• Placebo
• Standard of Care

Conditions studied

• Inflammatory Bowel Disease — all drugs for Inflammatory Bowel Disease →

Sponsor

Galapagos NV — full company profile →

Who can join

Adults 21 to 65, male only, with Inflammatory Bowel Disease. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Percentage of Participants With a ≥ 50% Decrease From Baseline in Sperm Concentration at Week 13 Primary · 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.

Group	Value	95% CI
Filgotinib	1.5
Placebo	9.0

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

Group	Value	95% CI
Filgotinib/DB Filgotinib (Responder)	5.0
Filgotinib/OL Filgotinib (Nonresponder)	0
Placebo/DB Placebo (Responder)	7.9
Placebo/OL Filgotinib (Nonresponder)	11.8

Change From Baseline in Sperm Total Motility at Week 13 Secondary · Baseline, Week 13

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

Group	Value	95% CI
Filgotinib	-0.3	-1.6 – 1.7
Placebo	0.4	-1.3 – 1.5

Change From Baseline in Sperm Total Motility at Week 26 Secondary · 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 asses

Group	Value	95% CI
Filgotinib/DB Filgotinib (Responder)	-2.3	-4.7 – -0.3
Filgotinib/OL Filgotinib (Nonresponder)	-1.5	-5.8 – 2.6
Placebo/DB Placebo (Responder)	0.0	-3.4 – 2.4
Placebo/OL Filgotinib (Nonresponder)	0.8	-7.3 – 5.8

Change From Baseline in Total Sperm Count at Week 13 Secondary · Baseline, Week 13

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

Group	Value	95% CI
Filgotinib	-11.6	-19.8 – 9.7
Placebo	-9.5	-23.8 – 0.6

Change From Baseline in Total Sperm Count at Week 26 Secondary · 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 asses

Group	Value	95% CI
Filgotinib/DB Filgotinib (Responder)	2.0	-19.6 – 17.2
Filgotinib/OL Filgotinib (Nonresponder)	-4.6	-42.3 – 18.3
Placebo/DB Placebo (Responder)	-4.1	-39.8 – 15.9
Placebo/OL Filgotinib (Nonresponder)	12.7	-61.4 – 40.8

Change From Baseline in Sperm Concentration at Week 13 Secondary · Baseline, Week 13

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

Group	Value	95% CI
Filgotinib	1.0	-2.2 – 3.9
Placebo	0.7	-2.7 – 1.7

Change From Baseline in Sperm Concentration at Week 26 Secondary · 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 asses

Group	Value	95% CI
Filgotinib/DB Filgotinib (Responder)	1.2	-3.2 – 10.8
Filgotinib/OL Filgotinib (Nonresponder)	-0.6	-8.5 – 23.0
Placebo/DB Placebo (Responder)	0.8	-2.4 – 5.3
Placebo/OL Filgotinib (Nonresponder)	-3.7	-11.1 – 15.7

Change From Baseline in Ejaculate Volume at Week 13 Secondary · Baseline, Week 13

The normal range for ejaculate volume is ≥1.5 mL.

Group	Value	95% CI
Filgotinib	-0.2	-0.3 – 0.1
Placebo	-0.1	-0.3 – 0.0

Change From Baseline in Ejaculate Volume at Week 26 Secondary · 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 asses

Group	Value	95% CI
Filgotinib/DB Filgotinib (Responder)	0.0	-0.5 – 0.2
Filgotinib/OL Filgotinib (Nonresponder)	-0.3	-0.8 – 0.2
Placebo/DB Placebo (Responder)	-0.2	-0.5 – 0.1
Placebo/OL Filgotinib (Nonresponder)	-0.1	-0.7 – 0.4

Change From Baseline in Percent Normal Sperm Morphology at Week 13 Secondary · Baseline, Week 13

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

Group	Value	95% CI
Filgotinib	2	-1 – 4
Placebo	1	-1 – 2

Change From Baseline in Percent Normal Sperm Morphology at Week 26 Secondary · 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 asses

Group	Value	95% CI
Filgotinib/DB Filgotinib (Responder)	3	1 – 5
Filgotinib/OL Filgotinib (Nonresponder)	1	-2 – 3
Placebo/DB Placebo (Responder)	2	-4 – 5
Placebo/OL Filgotinib (Nonresponder)	2	-2 – 3

Adverse events — posted to ClinicalTrials.gov

Time frame: From first dose up to Week 226. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Filgotinib

Serious: 3/92 (3%)

Deaths: 0/92

Placebo

Serious: 2/70 (3%)

Deaths: 0/70

Serious adverse events (4 terms)

Reaction	System	Filgotinib	Placebo
Colitis ulcerative	Gastrointestinal disorders	—	—
Crohn's disease	Gastrointestinal disorders	—	—
COVID-19	Infections and infestations	—	—
Pneumonia	Infections and infestations	—	—

Other adverse events (9 terms — click to expand)

Reaction	System	Filgotinib	Placebo
Nasopharyngitis	Infections and infestations	—	—
Colitis ulcerative	Gastrointestinal disorders	—	—
COVID-19	Infections and infestations	—	—
Headache	Nervous system disorders	—	—
Gastritis	Gastrointestinal disorders	—	—
Latent tuberculosis	Infections and infestations	—	—
Abdominal pain	Gastrointestinal disorders	—	—
Pyrexia	General disorders	—	—
Furuncle	Infections and infestations	—	—

Most-reported serious reactions: Colitis ulcerative, Crohn's disease, COVID-19, Pneumonia.

Data from ClinicalTrials.gov NCT03201445 adverse events section.

Sponsor's own description

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.

Publications & conference data

No peer-reviewed publications indexed yet for this trial.