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

Inflammatory Bowel Disease Clinical Trial

— MANTA  

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03201445
• Other study ID #: GS-US-418-4279
• Secondary ID: 2017-000402-38
• Status: Terminated
• Phase: Phase 2
• Start date: July 11, 2017
• Est. completion date: October 24, 2023

Study information

• Verified date: November 2023
• Source: Galapagos NV
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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); Monitoring Phase (MP; up to 52 weeks); and Long-term Extension (LTE) Phase (after Week 26 or end of OL Filgotinib Phase for up to 195 weeks).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 139
• Est. completion date: October 24, 2023
• Est. primary completion date: November 20, 2020
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 21 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Inflammatory Bowel Disease
• Inflammatory Bowel Diseases
• Intestinal Diseases

Intervention

Drug:
• Filgotinib
200 mg tablet administered orally once daily
• Placebo
Placebo to match filgotinib tablet administered orally once daily
• 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.

Locations

Country	Name	City	State
Australia	Monash Medical Centre	Clayton	Victoria
Austria	AKH Wien - Universitatsklinik fur Innere Medizin III	Vienna
Germany	Medizinische Hochschule Hannover	Hannover
India	Kaizen Hospital	Ahmedabad
India	SP Medical college & AG Hospitals	Bikaner
India	Maharaja Agrasen Hospital	Dehli
India	Nizam's Institute of Medical Sciences	Hyderabad
India	SMS Medical College and Hospital	Jaipur
India	SR Kalla Memorial Gastro and General Hospital	Jaipur
India	Om Sai Onco Surgery Center	Kolhapur
India	Institute of Post Graduate Medical Education and Research (IPGMER)	Kolkata
India	Radha Krishna Critical Care & General Hospital	Kota
India	Dayanand Medical College & Hospital	Ludhiana
India	Crescent Hospital and Heart Centre	Nagpur
India	Rahate Surgical Hospital	Nagpur
India	All India Institute of Medical Sciences	New Delhi
India	Batra Hospital and Medical Research Center	New Delhi
India	Sir Ganga Ram Hospital	New Delhi
India	Seth GS medical college and KEM hospital	Parel	Mumbai
India	Shri Griraj Multispeciality Hospital	Rajkot
India	Gandhi Hospital	Secunderabad
India	Institute of Gastroenterology & Liver Disease, Sunshine Hospitals	Secunderabad
India	BAPS Pramukh Swami Hospital	Surat
India	Surat Institute of Digestive Sciences	Surat	Gujarat
India	Sterling Hospital	Vadodara
India	Samvedna Hospital	Varanasi
New Zealand	Wellington Hospital	Newtown
Poland	Osrodek Badan Klinicznych Cinsante S.C Ewa Galczak-Nowak	Bydgoszcz
Poland	Krakowskie Centrum Medyczne	Kraków
Poland	Santa Familia, Centrum Badan Profilaktyki i Leczenia	Lódz
Poland	Endoskopia Sp.z o.o	Sopot
Poland	Bodyclinic Alicja Pasnik	Warsaw
Romania	S.C. Policlinica Dr. Citu S.R.L - Gastroenterologie	Timisoara
Russian Federation	Olla-Med, Llc	Moscow
Russian Federation	State Budgetary Healthcare Institution, Pensa Regional Clinical Hospital n.a N.N Burdenko	Penza
Russian Federation	State Budgetary Educational Institution of Higher Professional Education "Rostov State Medical University" of the Ministry of Health of Russian Fedn.	Rostov-on-Don
Russian Federation	Saint Petersburg State Budgetary Healthcare Institution "City Hospital # 26"	Saint Petersburg
Ukraine	Municipal Health Care Institution "Regional Hospital of War Veterans", Therapeutic Department No. 1	Kharkiv
Ukraine	Kyiv City Clinical Hospital #18, Proctology Department	Kiev
Ukraine	Vinnytsia Regional Clinical Hospital of War Veterans, Therapeutics Department No. 2	Vinnitsa
Ukraine	Medical Center LLC "Health Clinic", Medical Clinical Investigational Center	Vinnitsya
Ukraine	Vinnytsia Regional Clinical Hospital named after M.I. Pirogov, Gastroenterology Department	Vinnitsya
Ukraine	Vinnytsia Regional Clinical Hospital of War Veterans, Therapeutics Department No.1	Vinnytsya
Ukraine	Municipal Non-profit Enterprise "Zaporizhzhia Regional Clinical Hospital" of Zaporizhzhia Regional Council,	Zaporizhzhya
Ukraine	Municupal Institution "Zaporizhzhia City Multidisciplinary Clinic #9" Gastrointestinal Surgery Department,	Zaporizhzhya
United Kingdom	Cambridge University Hospitals NHS Foundation Trust	Cambridge
United States	Texas Clinical Research Institute	Arlington	Texas
United States	Clinical Research Institute of Michigan, LLC	Chesterfield	Michigan
United States	Gastro One	Germantown	Tennessee
United States	Florida Research Institute	Lakewood Ranch	Florida
United States	Great Lakes Gastroenterology Research, LLC	Mentor	Ohio
United States	University of Miami Crohn's and Colitis Center	Miami	Florida
United States	Delta Research Partners	Monroe	Louisiana
United States	One Health Research Clinic, Inc	Norcross	Georgia
United States	Naval Medical Center San Diego	San Diego	California
United States	Texas Digestive Disease Consultants	Southlake	Texas

Sponsors (2)

Lead Sponsor	Collaborator
Galapagos NV	Gilead Sciences

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Germany,  India,  New Zealand,  Poland,  Romania,  Russian Federation,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	Change From Baseline in Sperm Total Motility at Week 13	The normal range for sperm total motility is =40%.	Baseline, Week 13
Secondary	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
Secondary	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
Secondary	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
Secondary	Change From Baseline in Sperm Concentration at Week 13	The normal range for sperm concentration is =15 million sperm cells/mL.	Baseline, Week 13
Secondary	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
Secondary	Change From Baseline in Ejaculate Volume at Week 13	The normal range for ejaculate volume is =1.5 mL.	Baseline, Week 13
Secondary	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
Secondary	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
Secondary	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