To evaluate the testicular safety of filgotinib in adult males with ulcerative colitis MedDRA version: 20.1 Level: LLT Classification code 10045365 Term: Ulcerative colitis System Organ Class: 100000004856
Conditions
Interventions
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
Sponsors
Gilead Sciences, Inc.
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: For a full list please see the study protocol. - Male subjects who are between the ages of 25 and 55 (inclusive) on the day of signing informed consent - Documented diagnosis of UC of at least 4 months AND with a minimum disease extent of 15 cm from the anal verge. Documentation should include endoscopic and histopathologic evidence of UC as follows: a) The criteria for documentation of UC based on endoscopy will be medical record documentation of, or an endoscopy report dated = 4 months before enrollment, which shows features consistent with UC, determined by the procedure performing physician b) The criteria for documentation of UC based on histopathology will be medical record documentation of or a histopathology report indicating features consistent with UC as determined by the pathologist - Have moderately to severely active UC defined as a Mayo Clinic Score = 6 with a physician global assessment (PGA) of moderately to severely active UC (PGA of 2 or 3) and local endoscopic subscore at screening or in the prior 60 days of = 2 - 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 - May be receiving 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) provided the dose prescribed has been stable for 2 weeks prior to randomization; dose should be stable for the first 13 weeks if possible, upon which a steroid taper may commence at the discretion of the investigator. - Provide semen samples at Screening that meet the following minimum criteria: a) 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 = 4% - 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 range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 250 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
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 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 - Diagnosis of UC that occurred > 20 years ago (eg, duration of disease must have been < 20 years)
Design outcomes
Secondary
| Measure | Time frame |
|---|---|
| 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;Timepoint(s) of evaluation of this end point: End of week 26 | — |
Primary
| Measure | Time frame |
|---|---|
| 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;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 | — |
Countries
Australia, Austria, Belgium, Canada, Czech Republic, Germany, Hungary, India, Italy, Netherlands, New Zealand, Poland, Portugal, Romania, Russian Federation, Spain, Sri Lanka, Sweden, Ukraine, United Kingdom, United States
Contacts
Public ContactClinical Trials Mailbox
Gilead Sciences International Ltd.
Outcome results
None listed