A clinical trail to evaluate the testicular safety of Filgotinib in adult males with Moderately to Severely Active Inflammatory Bowel Disease

• Register: EUCTR
• Last refreshed on: 4 December 2023
• Main ID: EUCTR2017-000402-38-DE
• Date of registration: 27/10/2017
• Prospective Registration: Yes
• Primary sponsor: Galapagos NV
• Public title: A clinical trail to evaluate the testicular safety of Filgotinib in adult males with Moderately to Severely Active Inflammatory Bowel Disease
• Scientific 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
• Date of first enrolment: 23/01/2018
• Target sample size: 250
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-000402-38
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Austria, Belgium, Canada, Germany, India, Netherlands, New Zealand, Poland, Portugal, Romania, Russian Federation, Spain, Sweden, Taiwan, Ukraine, United Kingdom, United States

Contacts

• Name: Clinical Trials Information Desk
• Affiliation: Galapagos NV

• Name: Clinical Trials Information Desk
• Affiliation: Galapagos NV

Key inclusion & exclusion criteria

Inclusion criteria:
For a full list please see the study protocol.

- Males between the age of 21 and 65 (inclusive) on the day of signing informed consent

- Documented diagnosis of UC or CD of at least 4 months duration.
Documentation must include endoscopic and histopathologic documentation as follows:
a) UC
i) Medical record documentation of, or an endoscopy report dated = 4 months before randomization, which shows features consistent with UC, determined by the procedure performing physician, AND
ii) Medical record documentation of, or a histopathology report indicating features consistent with UC as determined by the pathologist,
AND
Note: Subject also needs to have minimum disease extent of 15 cm from the anal verge
b) CD
i) Medical record documentation of, or an ileocolonoscopy (full colonoscopy with intubation of terminal ileum) reported dated = 4 months before randomization, which shows features consistent with CD, determined by the procedure performing physician, AND
ii) Medical record documentation of, or a histopathology report indicating features consistent with CD as determined by the pathologist

- Moderately to severely active UC, or moderately to severely active CD, assessed locally and defined by:
a) UC
I) Mayo Clinic Score (MCS; Appendix 3) = 6, PGA of 2 or 3, and endoscopic subscore = 2, at Screening or in the prior 90 days
b) CD
I) CDAI total score (Appendix 9) = 220, AND
ii) Evidence of active inflammation, with a total score of = 6 by the Simple Endosopic Activity Score in the Crohn's Disease (SES-CD; Appendix 10), OR if disease is limited to the ileum and/or right colon, a combined SES-CD score = 4 in these 2 segments, at Screening or in the prior 90 days

- Previously demonstrated an inadequate clinical response, loss of response to, or intolerance of at least one of the following agents (depending on current country treatment recommendations/guidelines):
a) corticosteroids
b) immunomodulators
c) TNFa antagonists
d) vedolizumab
e) Ustekinumab (criterion applicable only to subjects with CD)

- May be receiving 1 or more of the following drugs (subjects on these therapies must be willing to remain on stable doses for the noted times):
a) 5-aminosalicylate (5-ASA) compounds provided the dose prescribed has been stable for at least 4 weeks prior to randomization; dose must remain stable for the first 13 weeks after randomization
b) Azathioprine, 6-MP, or MTX provided the dose prescribed has been stable for 4 weeks prior to randomization; dose of MTX must remain stable for 26 weeks and dose of AZA/6-MP must remain stable for first 13 weeks but can be adjusted if indicated between 13 and 26 weeks.
c) Corticosteroid therapy (prednisone prescribed at a stable dose = 20 mg/day or budesonide prescribed at a stable dose of = 9 mg/day); dose should not be changed during the first 13 weeks. A steroid taper should only commence after Week 13.

- The mean of 2 separate semen samples collected at Screening visit must meet the following minimum criteria (in accordance with Section 6.13 and Figure 6-1): Semen volume = 1.5 mL, total sperm per ejaculate = 39 million, sperm concentration = 15 million per mL, sperm total motility = 40%, and normal sperm morphology = 30%

- LH, FSH, inhibin B, and total testosterone values within 20% of laboratory normal reference ranges at Screening

- Be up to date on colorectal cancer surveillance as per local guidelines prior to screening.
Are the trial subjects under 18? no
Number of subjects for this age rang
Exclusion criteria:
For a full list please see the study protocol.

- Previously documented problems with male reproductive health including (but not limited to) known hypothalamic-pituitary disorders (eg, pituitary macroadenomas, pituitary infarction, hyperprolactinemia, panhypopituitarism), primary hypogonadism (eg, cryptorchidism, Klinefelter’s syndrome)

- Prior diagnosis of male infertility (including reduced fertility), or history of anti-sperm antibodies

- Clinically significant (per judgment of investigator) varicocele or spermatocele

- History of radiation to the testicles

- History of clinically significant trauma to, or surgery on, the testicles, including vasectomy

- Current treatment with antiandrogen therapy (including but not limited to spironolactone or oral ketoconazole), or treatment within 4 weeks of Screening

- Current treatment with testosterone replacement therapy, or treatment within 12 weeks of Screening

- Presence of disorders of sperm transport (including but not limited to retrograde ejaculation and immotile cilia syndrome)

- Clinically significant urinary tract infection, prostatitis, epididymitis, including sexually transmitted infection within 4 weeks of Screening

- Current use of sulfasalazine or use of sulfasalazine within 26 weeks of Screening; sulfasalazine is not permitted at any point during the study

- Use of any TNFa antagonist or vedolizumab within 8 weeks prior to screening, ustekinumab 12 weeks prior to screening, or any other biologic agent within 8 weeks prior to Screening or within 5 half-lives of the biologic agent prior to screening, whichever is longer

- Currently have complicatioins of CD as any of the following:
a) Symptomatic strictures, OR
b) Severe (impassable) rectal/anal stenosis, OR
c) Fistulae, OR
d) Short bowel syndrome, OR
e) Any other complications which could preclude the use of the CDAI to assess response to therapy, or would possibly confound the evaluation of benefit from treatment with filgotinib


Age minimum:
Age maximum:
Gender:
Female: no
Male: yes

Health Condition(s) or Problem(s) studied

To evaluate the testicular safety of filgotinib in adult males with moderately to severely Active Inflammatory Bowel Disease
MedDRA version: 20.1 Level: LLT Classification code 10045365 Term: Ulcerative colitis System Organ Class: 100000004856
MedDRA version: 20.0 Level: LLT Classification code 10013099 Term: Disease Crohns System Organ Class: 100000004856

Therapeutic area: Diseases [C] - Digestive System Diseases [C06]

Intervention(s)

Product Code: GS-6034
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: FILGOTINIB
Current Sponsor code: GS-6034
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 200-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Primary end point(s): The primary endpoint is the proportion of subjects with a = 50% decrease from baseline in sperm concentration at Week 13.

Timepoint(s) of evaluation of this end point: End of week 13

Main Objective: To evaluate the effect of filgotinib on testicular function as defined by the proportion of subjects with a = 50% decrease from baseline in sperm concentration at Week 13

Secondary Objective: To evaluate the effect of filgotinib on testicular function as defined by the proportion of subjects with a = 50% decrease from baseline in sperm concentration at Week 26
To evaluate the effect of filgotinib on sperm total motility at Weeks 13 and 26
To evaluate the effect of filgotinib on total sperm count at Weeks 13 and 26
To evaluate the effect of filgotinib on the change from baseline in sperm concentration at Weeks 13 and 26
To evaluate the effect of filgotinib on ejaculate volume at Weeks 13 and 26
To evaluate the effect of filgotinib on sperm morphology at Weeks 13 and 26

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: End of week 26

Secondary end point(s): The proportion of subjects with a = 50% decrease from baseline in sperm concentration at Week 26
Change from baseline in percent motile sperm at Weeks 13 and 26
Change from baseline in total sperm count at Weeks 13 and 26
Change from baseline in sperm concentration at Weeks 13 and 26
Change from baseline in ejaculate volume at Weeks 13 and 26
Change from baseline in percent normal sperm morphology at Weeks 13 and 26

Secondary ID(s)

GS-US-418-4279

2017-000402-38-GB

Source(s) of Monetary Support

Galapagos NV

Ethics review

Status: Approved
Approval date: 23/01/2018
Contact:

Results

• Results available: Yes
• Date Posted: 20/07/2023
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2017-000402-38/results