Inflammatory Bowel Disease
Conditions
Brief 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.
Detailed 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); 4) Monitoring Phase (MP; up to 52 weeks); and 5) Long-term Extension (LTE) Phase (after Week 26 or end of OL Filgotinib Phase for up to 195 weeks).
Interventions
DRUGFilgotinib
200 mg tablet administered orally once daily
DRUGPlacebo
Placebo to match filgotinib tablet administered orally once daily
DRUGStandard 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.
Sponsors
Gilead Sciences
Galapagos NV
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
MALE
Age
21 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With a ≥ 50% Decrease From Baseline in Sperm Concentration at Week 13 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Sperm Total Motility at Week 13 | Baseline, Week 13 | The normal range for sperm total motility is ≥40%. |
| Change From Baseline in Sperm Total Motility at Week 26 | 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 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%. |
| Change From Baseline in Total Sperm Count at Week 13 | Baseline, Week 13 | The normal range for total sperm count is ≥ 39 million sperm cells/ejaculate. |
| Change From Baseline in Total Sperm Count at Week 26 | 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 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. |
| Change From Baseline in Sperm Concentration at Week 13 | Baseline, Week 13 | The normal range for sperm concentration is ≥15 million sperm cells/mL. |
| Percentage of Participants With a ≥ 50% Decrease From Baseline in Sperm Concentration at Week 26 | 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. 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. |
| Change From Baseline in Ejaculate Volume at Week 13 | Baseline, Week 13 | The normal range for ejaculate volume is ≥1.5 mL. |
| Change From Baseline in Ejaculate Volume at Week 26 | 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 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. |
| Change From Baseline in Percent Normal Sperm Morphology at Week 13 | Baseline, Week 13 | The normal range for percent normal sperm morphology is ≥30% normal sperms. |
| Change From Baseline in Percent Normal Sperm Morphology at Week 26 | 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 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. |
| Change From Baseline in Sperm Concentration at Week 26 | 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 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. |
Countries
Australia, Austria, Germany, India, New Zealand, Poland, Romania, Russia, Ukraine, United Kingdom, United States
Participant flow
Recruitment details
Participants were enrolled at study sites in Australia, Austria, Germany, India, New Zealand, Poland, Romania, Russian Federation, Ukraine, United Kingdom, and United States. The first participant was screened on 11 July 2017. A total of 323 participants were screened of which 139 participants were randomized into the study.
Pre-assignment details
Study had 5 parts: Part A: Double-Blind Phase (DB Phase; Day 1 up to Week 13); Part B: DB Phase (Week 13 up to Week 26); Open-label (OL) 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 Phase for up to 195 weeks).
Participants by arm
| Arm | Count |
|---|---|
| Filgotinib Participants received filgotinib 200 mg tablet, orally, once daily up to Week 13 in the DB phase (Part A). At Week 13, participants who were IBD responders, without meeting pre-specified sperm decrease thresholds, continued DB phase treatment up to Week 26 (Part B). Participants who were IBD non-responders at Week 13 (end of Part A) or had disease worsening after Week 13 and prior to Week 26 (in Part B), and whose sperm parameters did not meet a prespecified decrease threshold, entered the OL Phase and received OL filgotinib 200 mg, tablet, orally, once daily for up to Week 13 during the OL phase. At Week 26/OL Week 13, participants who were IBD responders and who had not experienced disease worsening, and whose sperm parameters did not meet a prespecified decrease threshold, continued receiving the same study drug they were responding to (ie, blinded study drug or OL filgotinib) as part of the LTE for up to 195 weeks. Participants who met pre-specified sperm decrease threshold(s) at any postbaseline visit discontinued study drug and switched to a SOC regimen selected by the investigator (in accordance with the protocol) and entered the MP for up to 52 weeks. | 69 |
| Placebo Participants received placebo (matched to filgotinib) tablet, orally, once daily up to Week 13 in the DB phase (Part A). At Week 13, participants who were IBD responders, without meeting pre-specified sperm decrease thresholds, continued DB phase treatment up to Week 26 (Part B). Participants who were IBD non-responders at Week 13 (end of Part A) or had disease worsening after Week 13 and prior to Week 26 (in Part B), and whose sperm parameters did not meet a prespecified decrease threshold, entered the OL Phase and received OL filgotinib 200 mg, tablet, orally, once daily for up to Week 13 during the OL phase. At Week 26/OL Week 13, participants who were IBD responders and who had not experienced disease worsening, and whose sperm parameters did not meet a prespecified decrease threshold, continued receiving the same study drug they were responding to (ie, blinded study drug or OL filgotinib) as part of the LTE for up to 195 weeks. Participants who met pre-specified sperm decrease threshold(s) at any postbaseline visit discontinued study drug and switched to SOC regimen selected by the investigator (in accordance with the protocol) and entered the MP for up to 52 weeks. | 70 |
| Total | 139 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| LTE: DB Study Drug (up to Week 195) | Adverse Event | 9 | 10 |
| LTE: DB Study Drug (up to Week 195) | Lost to Follow-up | 0 | 1 |
| LTE: DB Study Drug (up to Week 195) | Physician Decision | 0 | 2 |
| LTE: DB Study Drug (up to Week 195) | Pre-Specified Decrease In Sperm Parameters (Switched to MP) | 6 | 7 |
| LTE: DB Study Drug (up to Week 195) | Study Terminated By Sponsor | 11 | 5 |
| LTE: DB Study Drug (up to Week 195) | Withdrawal by Subject | 4 | 4 |
| LTE: OL Study Drug (Up to Week 195) | Adverse Event | 3 | 2 |
| LTE: OL Study Drug (Up to Week 195) | Physician Decision | 1 | 2 |
| LTE: OL Study Drug (Up to Week 195) | Pre-Specified Decrease In Sperm Parameters (Switched to MP) | 5 | 3 |
| LTE: OL Study Drug (Up to Week 195) | Progressive Disease | 2 | 0 |
| LTE: OL Study Drug (Up to Week 195) | Study Terminated By Sponsor | 6 | 6 |
| LTE: OL Study Drug (Up to Week 195) | Withdrawal by Subject | 1 | 1 |
| Monitoring Phase (Up to Week 52) | Study Terminated By Sponsor | 0 | 1 |
| Monitoring Phase (Up to Week 52) | Withdrawal by Subject | 1 | 1 |
| OL Phase (13 Weeks) | Adverse Event | 0 | 2 |
| OL Phase (13 Weeks) | Withdrawal by Subject | 2 | 1 |
| Part A DB Phase (Through Week 13) | Lost to Follow-up | 1 | 0 |
| Part A DB Phase (Through Week 13) | Protocol Violation | 0 | 1 |
| Part A DB Phase (Through Week 13) | Withdrawal by Subject | 0 | 2 |
| Part B DB Phase (Week 13 to 26) | Adverse Event | 1 | 0 |
| Part B DB Phase (Week 13 to 26) | Progressive Disease | 2 | 0 |
Baseline characteristics
| Characteristic | Filgotinib | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 36 years STANDARD_DEVIATION 8.5 | 34 years STANDARD_DEVIATION 8.4 | 35 years STANDARD_DEVIATION 8.5 |
| Ejaculate Volume | 3.2 mL STANDARD_DEVIATION 1.2 | 3.0 mL STANDARD_DEVIATION 1.48 | 3.1 mL STANDARD_DEVIATION 1.35 |
| Percent Normal Sperm Morphology | 41 percentage of normal sperm STANDARD_DEVIATION 6.4 | 41 percentage of normal sperm STANDARD_DEVIATION 5.5 | 41 percentage of normal sperm STANDARD_DEVIATION 6 |
| Race/Ethnicity, Customized Ethnicity Hispanic or Latino | 1 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Ethnicity Not Hispanic or Latino | 68 Participants | 68 Participants | 136 Participants |
| Race/Ethnicity, Customized Ethnicity Not Permitted | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Race American Indian or Alaska Native | 2 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Race Asian | 37 Participants | 38 Participants | 75 Participants |
| Race/Ethnicity, Customized Race Black or African American | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Race Not Permitted | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Race White | 29 Participants | 31 Participants | 60 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 69 Participants | 70 Participants | 139 Participants |
| Sperm Concentration | 63.4 million sperm cells/milliliter (mL) STANDARD_DEVIATION 34.34 | 61.8 million sperm cells/milliliter (mL) STANDARD_DEVIATION 34.96 | 62.6 million sperm cells/milliliter (mL) STANDARD_DEVIATION 34.53 |
| Sperm Total Motility | 59.6 percentage of motile sperm STANDARD_DEVIATION 11.33 | 58.6 percentage of motile sperm STANDARD_DEVIATION 10.94 | 59.1 percentage of motile sperm STANDARD_DEVIATION 11.11 |
| Total Sperm Count | 190.6 million sperm cells/ejaculate STANDARD_DEVIATION 107.08 | 171.1 million sperm cells/ejaculate STANDARD_DEVIATION 100.74 | 180.8 million sperm cells/ejaculate STANDARD_DEVIATION 104.02 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 92 | 0 / 70 |
| other Total, other adverse events | 47 / 92 | 24 / 70 |
| serious Total, serious adverse events | 3 / 92 | 2 / 70 |
Outcome results
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.
Time frame: Baseline to Week 13
Population: The Semen Analysis Set included all randomized and treated (≥ 1 dose of double-blind study drug) participants who had 2 semen samples that were eligible for mean calculation at baseline and at the Week 13 analysis visit with the date of the first chronologic semen sample used for purposes of assigning analysis visit windows.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Filgotinib | Percentage of Participants With a ≥ 50% Decrease From Baseline in Sperm Concentration at Week 13 | 1.5 percentage of participants |
| Placebo | Percentage of Participants With a ≥ 50% Decrease From Baseline in Sperm Concentration at Week 13 | 9.0 percentage of participants |
95% CI: [-16.3, 0.7]
Secondary
Change From Baseline in Ejaculate Volume at Week 13
The normal range for ejaculate volume is ≥1.5 mL.
Time frame: Baseline, Week 13
Population: Participants in the Semen Analysis Set were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Filgotinib | Change From Baseline in Ejaculate Volume at Week 13 | -0.2 mL |
| Placebo | Change From Baseline in Ejaculate Volume at Week 13 | -0.1 mL |
95% CI: [-0.1, 0.3]
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.
Time frame: Baseline, Week 26
Population: Participants in the Week 26 Semen Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Filgotinib | Change From Baseline in Ejaculate Volume at Week 26 | 0.0 mL |
| Placebo | Change From Baseline in Ejaculate Volume at Week 26 | -0.3 mL |
| Placebo/DB Placebo (Responder) | Change From Baseline in Ejaculate Volume at Week 26 | -0.2 mL |
| Placebo/OL Filgotinib (Nonresponder) | Change From Baseline in Ejaculate Volume at Week 26 | -0.1 mL |
Secondary
Change From Baseline in Percent Normal Sperm Morphology at Week 13
The normal range for percent normal sperm morphology is ≥30% normal sperms.
Time frame: Baseline, Week 13
Population: Participants in the Semen Analysis Set were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Filgotinib | Change From Baseline in Percent Normal Sperm Morphology at Week 13 | 2 percentage of normal sperms |
| Placebo | Change From Baseline in Percent Normal Sperm Morphology at Week 13 | 1 percentage of normal sperms |
95% CI: [0, 4]
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.
Time frame: Baseline, Week 26
Population: Participants in the Week 26 Semen Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Filgotinib | Change From Baseline in Percent Normal Sperm Morphology at Week 26 | 3 percentage of normal sperms |
| Placebo | Change From Baseline in Percent Normal Sperm Morphology at Week 26 | 1 percentage of normal sperms |
| Placebo/DB Placebo (Responder) | Change From Baseline in Percent Normal Sperm Morphology at Week 26 | 2 percentage of normal sperms |
| Placebo/OL Filgotinib (Nonresponder) | Change From Baseline in Percent Normal Sperm Morphology at Week 26 | 2 percentage of normal sperms |
Secondary
Change From Baseline in Sperm Concentration at Week 13
The normal range for sperm concentration is ≥15 million sperm cells/mL.
Time frame: Baseline, Week 13
Population: Participants in the Semen Analysis Set were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Filgotinib | Change From Baseline in Sperm Concentration at Week 13 | 1.0 million sperm cells/mL |
| Placebo | Change From Baseline in Sperm Concentration at Week 13 | 0.7 million sperm cells/mL |
95% CI: [-2.8, 4.9]
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.
Time frame: Baseline, Week 26
Population: Participants in the Week 26 Semen Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Filgotinib | Change From Baseline in Sperm Concentration at Week 26 | 1.2 million sperm cells/mL |
| Placebo | Change From Baseline in Sperm Concentration at Week 26 | -0.6 million sperm cells/mL |
| Placebo/DB Placebo (Responder) | Change From Baseline in Sperm Concentration at Week 26 | 0.8 million sperm cells/mL |
| Placebo/OL Filgotinib (Nonresponder) | Change From Baseline in Sperm Concentration at Week 26 | -3.7 million sperm cells/mL |
Secondary
Change From Baseline in Sperm Total Motility at Week 13
The normal range for sperm total motility is ≥40%.
Time frame: Baseline, Week 13
Population: Participants in the Semen Analysis Set were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Filgotinib | Change From Baseline in Sperm Total Motility at Week 13 | -0.3 percentage of motile sperms |
| Placebo | Change From Baseline in Sperm Total Motility at Week 13 | 0.4 percentage of motile sperms |
95% CI: [-2.1, 1.8]
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%.
Time frame: Baseline, Week 26
Population: Participants in the Week 26 Semen Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Filgotinib | Change From Baseline in Sperm Total Motility at Week 26 | -2.3 percentage of motile sperms |
| Placebo | Change From Baseline in Sperm Total Motility at Week 26 | -1.5 percentage of motile sperms |
| Placebo/DB Placebo (Responder) | Change From Baseline in Sperm Total Motility at Week 26 | 0.0 percentage of motile sperms |
| Placebo/OL Filgotinib (Nonresponder) | Change From Baseline in Sperm Total Motility at Week 26 | 0.8 percentage of motile sperms |
Secondary
Change From Baseline in Total Sperm Count at Week 13
The normal range for total sperm count is ≥ 39 million sperm cells/ejaculate.
Time frame: Baseline, Week 13
Population: Participants in the Semen Analysis Set were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Filgotinib | Change From Baseline in Total Sperm Count at Week 13 | -11.6 million sperm cells/ejaculate |
| Placebo | Change From Baseline in Total Sperm Count at Week 13 | -9.5 million sperm cells/ejaculate |
95% CI: [-13.4, 24.7]
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.
Time frame: Baseline, Week 26
Population: Participants in the Week 26 Semen Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Filgotinib | Change From Baseline in Total Sperm Count at Week 26 | 2.0 million sperm cells/ejaculate |
| Placebo | Change From Baseline in Total Sperm Count at Week 26 | -4.6 million sperm cells/ejaculate |
| Placebo/DB Placebo (Responder) | Change From Baseline in Total Sperm Count at Week 26 | -4.1 million sperm cells/ejaculate |
| Placebo/OL Filgotinib (Nonresponder) | Change From Baseline in Total Sperm Count at Week 26 | 12.7 million sperm cells/ejaculate |
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.
Time frame: Baseline to Week 26
Population: Participants in the Week 26 Semen Analysis Set (included all participants who took ≥ 1 dose of study drug and had 2 evaluable samples at baseline and at ≥ 1 postbaseline measurement at/after Week 26 or OL Week 13) with available data were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Filgotinib | Percentage of Participants With a ≥ 50% Decrease From Baseline in Sperm Concentration at Week 26 | 5.0 percentage of participants |
| Placebo | Percentage of Participants With a ≥ 50% Decrease From Baseline in Sperm Concentration at Week 26 | 0 percentage of participants |
| Placebo/DB Placebo (Responder) | Percentage of Participants With a ≥ 50% Decrease From Baseline in Sperm Concentration at Week 26 | 7.9 percentage of participants |
| Placebo/OL Filgotinib (Nonresponder) | Percentage of Participants With a ≥ 50% Decrease From Baseline in Sperm Concentration at Week 26 | 11.8 percentage of participants |