Clinical Trials List
Protocol NumberGS-US-418-4279
NCT Number(ClinicalTrials.gov Identfier)NCT03201445
2018-10-01 - 2020-08-25
Phase II
Terminated6
ICD-9556.9
Ulcerative colitis, unspecified
A Randomized, Double-blind, Placebo-controlled Phase 2 Study to Evaluate the Testicular Safety of Filgotinib in Adult Males with Moderately to Severely Active Ulcerative Colitis
-
Trial Applicant
Pharmaceutical Research Associates Taiwan Inc.
-
Sponsor
Gilead Sciences
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Trial scale
Multi-Regional Multi-Center
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Update
2025/08/20
Investigators and Locations
The Actual Total Number of Participants Enrolled
0 Stop recruiting
The Actual Total Number of Participants Enrolled
0 Stop recruiting
The Actual Total Number of Participants Enrolled
0 Stop recruiting
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
Audit
None
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Audit
None
Co-Principal Investigator
- Yu-Chung Su Division of General Internal Medicine
- Huang-Ming Hu Division of General Internal Medicine
- Chao-Hung Kuo Division of General Internal Medicine
- I-CHEN WU Division of General Internal Medicine
- Chien-Yu Lu Division of General Internal Medicine
- Wen-Hung Hsu Division of General Internal Medicine
- Fang-Jung Yu Yu Division of General Internal Medicine
- HSIANG YAO SHIH Division of General Internal Medicine
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Condition/Disease
Ulcerative Colitis
Objectives
The primary objective of this study is:
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
The secondary objectives of this study include:
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
Test Drug
Filgotinib (GS-6034)
Active Ingredient
Filgotinib
Dosage Form
tablet
Dosage
200
Endpoints
Safety:
Semen will be collected as outlined in Section 6.14. Male hormones, including LH, FSH, inhibin B and testosterone (free and total) will be measured during this study as outlined in Section 6.2.
Other aspects of safety will be assessed by the reporting of AEs, clinical laboratory evaluations (hematology, chemistry and urinalysis), physical examination, vital signs, and 12-lead ECGs at various timepoints during the study.
Concomitant medication usage will also be assessed throughout the study.
Pharmacokinetics:
Plasma concentrations of filgotinib and its metabolite (GS-829845) will be analyzed.
Semen will be collected as outlined in Section 6.14. Male hormones, including LH, FSH, inhibin B and testosterone (free and total) will be measured during this study as outlined in Section 6.2.
Other aspects of safety will be assessed by the reporting of AEs, clinical laboratory evaluations (hematology, chemistry and urinalysis), physical examination, vital signs, and 12-lead ECGs at various timepoints during the study.
Concomitant medication usage will also be assessed throughout the study.
Pharmacokinetics:
Plasma concentrations of filgotinib and its metabolite (GS-829845) will be analyzed.
Inclution Criteria
Inclusion Criteria:
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
i) Active disease despite a history of at least an induction regimen of a dose equivalent to prednisone 20 mg daily for
2 weeks or intravenously (IV) for 1 week, OR
ii) Two failed attempts to taper steroids below a dose equivalent of 10 mg daily prednisone, OR
iii) History of steroid intolerance including, but not limited to, Cushing’s syndrome, osteopenia/osteoporosis,
hyperglycemia, insomnia, serious infections, depression, allergic reactions, mood disturbances, or any other
condition that contributed to discontinuation of the agent
b) Immunomodulators
i) Active disease despite a history of at least a 12-week regimen of oral azathioprine (≥ 2 mg/kg/day) or 6-MP
(≥ 1 mg/kg/day), or MTX (25 mg subcutaneously [SC] or intramuscularly [IM] per week for induction and ≥ 15 mg
IM per week for maintenance) OR
ii) History of intolerance to at least one immunomodulator
including but not limited to, serious infections,
hepatotoxicity, cytopenia, pancreatitis, thiopurine
methyltransferase (TPMT) genetic mutation, allergic
reactions, or any other condition that contributed to
discontinuation of the agent
c) TNFα antagonists
i) Active disease despite a history of at least one induction
regimen as follows:
Infliximab: Minimum induction regimen of 5 mg/kg
at 0, 2, and 6 weeks (in the European Union [EU],
duration of treatment of 14 weeks)
Adalimumab: An 8-week induction regimen
consisting of 160 mg (four 40-mg injections in one
day or two 40-mg injections per day for two
consecutive days) on Day 1, followed by a second
dose 2 weeks later (Day 15) of 80 mg and a 40 mg
dose 2 weeks later (Day 29), followed by a 40 mg
dose every other week until Week 8 (Day 57).
Golimumab: A minimum induction duration of
6 weeks (12 weeks in EU) is required for
golimumab, which includes 200 mg SC injection at
Week 0, followed by 100 mg at Week 2, and then
100 mg every 4 weeks OR
ii) Recurrence of symptoms during maintenance therapy with
the above agents, OR
iii) History of intolerance to any TNFα antagonists including,
but not limited to, serious infections, hepatotoxicity, heart
failure, allergic reactions, or any other condition that
contributed to discontinuation of the agent
d) Vedolizumab
i) Active disease despite a history of at least a 14-week
(10 weeks in EU) induction regimen of vedolizumab
consisting of 300 mg IV at Weeks 0, 2, and 6 OR
ii) History of intolerance to vedolizumab including, but not
limited to, serious infections, hepatotoxicity, cytopenia,
allergic reactions, or any other condition that contributed to
discontinuation of the agent
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 (based on the mean of the two collections in
accordance with Section 6.14):
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.
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
i) Active disease despite a history of at least an induction regimen of a dose equivalent to prednisone 20 mg daily for
2 weeks or intravenously (IV) for 1 week, OR
ii) Two failed attempts to taper steroids below a dose equivalent of 10 mg daily prednisone, OR
iii) History of steroid intolerance including, but not limited to, Cushing’s syndrome, osteopenia/osteoporosis,
hyperglycemia, insomnia, serious infections, depression, allergic reactions, mood disturbances, or any other
condition that contributed to discontinuation of the agent
b) Immunomodulators
i) Active disease despite a history of at least a 12-week regimen of oral azathioprine (≥ 2 mg/kg/day) or 6-MP
(≥ 1 mg/kg/day), or MTX (25 mg subcutaneously [SC] or intramuscularly [IM] per week for induction and ≥ 15 mg
IM per week for maintenance) OR
ii) History of intolerance to at least one immunomodulator
including but not limited to, serious infections,
hepatotoxicity, cytopenia, pancreatitis, thiopurine
methyltransferase (TPMT) genetic mutation, allergic
reactions, or any other condition that contributed to
discontinuation of the agent
c) TNFα antagonists
i) Active disease despite a history of at least one induction
regimen as follows:
Infliximab: Minimum induction regimen of 5 mg/kg
at 0, 2, and 6 weeks (in the European Union [EU],
duration of treatment of 14 weeks)
Adalimumab: An 8-week induction regimen
consisting of 160 mg (four 40-mg injections in one
day or two 40-mg injections per day for two
consecutive days) on Day 1, followed by a second
dose 2 weeks later (Day 15) of 80 mg and a 40 mg
dose 2 weeks later (Day 29), followed by a 40 mg
dose every other week until Week 8 (Day 57).
Golimumab: A minimum induction duration of
6 weeks (12 weeks in EU) is required for
golimumab, which includes 200 mg SC injection at
Week 0, followed by 100 mg at Week 2, and then
100 mg every 4 weeks OR
ii) Recurrence of symptoms during maintenance therapy with
the above agents, OR
iii) History of intolerance to any TNFα antagonists including,
but not limited to, serious infections, hepatotoxicity, heart
failure, allergic reactions, or any other condition that
contributed to discontinuation of the agent
d) Vedolizumab
i) Active disease despite a history of at least a 14-week
(10 weeks in EU) induction regimen of vedolizumab
consisting of 300 mg IV at Weeks 0, 2, and 6 OR
ii) History of intolerance to vedolizumab including, but not
limited to, serious infections, hepatotoxicity, cytopenia,
allergic reactions, or any other condition that contributed to
discontinuation of the agent
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 (based on the mean of the two collections in
accordance with Section 6.14):
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.
Exclusion Criteria
Exclusion Criteria:
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 TNFα 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)
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 TNFα 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)
The Estimated Number of Participants
-
Taiwan
10 participants
-
Global
250 participants
