Trial Outcomes & Findings for Study to Evaluate the Testicular Safety of Filgotinib in Adult Males With Moderately to Severely Active Inflammatory Bowel Disease (NCT NCT03201445)
NCT ID: NCT03201445
Last Updated: 2024-10-09
Results Overview
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.
Recruitment status
TERMINATED
Study phase
PHASE2
Target enrollment
139 participants
Primary outcome timeframe
Baseline to Week 13
Results posted on
2024-10-09
Participant Flow
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.
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).
Participant milestones
| Measure |
Filgotinib
Participants received filgotinib 200 milligrams (mg) tablet, orally, once daily up to Week 13 in the DB phase (Part A). At Week 13, participants who were inflammatory bowel disease (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 standard of care (SOC) regimen selected by the investigator (in accordance with the protocol) and entered the MP for up to 52 weeks.
|
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.
|
|---|---|---|
|
Part A DB Phase (Through Week 13)
STARTED
|
69
|
70
|
|
Part A DB Phase (Through Week 13)
COMPLETED
|
68
|
67
|
|
Part A DB Phase (Through Week 13)
NOT COMPLETED
|
1
|
3
|
|
Part B DB Phase (Week 13 to 26)
STARTED
|
45
|
38
|
|
Part B DB Phase (Week 13 to 26)
COMPLETED
|
42
|
38
|
|
Part B DB Phase (Week 13 to 26)
NOT COMPLETED
|
3
|
0
|
|
OL Phase (13 Weeks)
STARTED
|
24
|
23
|
|
OL Phase (13 Weeks)
COMPLETED
|
22
|
20
|
|
OL Phase (13 Weeks)
NOT COMPLETED
|
2
|
3
|
|
LTE: DB Study Drug (up to Week 195)
STARTED
|
38
|
34
|
|
LTE: DB Study Drug (up to Week 195)
COMPLETED
|
8
|
5
|
|
LTE: DB Study Drug (up to Week 195)
NOT COMPLETED
|
30
|
29
|
|
LTE: OL Study Drug (Up to Week 195)
STARTED
|
18
|
16
|
|
LTE: OL Study Drug (Up to Week 195)
COMPLETED
|
0
|
2
|
|
LTE: OL Study Drug (Up to Week 195)
NOT COMPLETED
|
18
|
14
|
|
Monitoring Phase (Up to Week 52)
STARTED
|
15
|
21
|
|
Monitoring Phase (Up to Week 52)
COMPLETED
|
14
|
19
|
|
Monitoring Phase (Up to Week 52)
NOT COMPLETED
|
1
|
2
|
Reasons for withdrawal
| Measure |
Filgotinib
Participants received filgotinib 200 milligrams (mg) tablet, orally, once daily up to Week 13 in the DB phase (Part A). At Week 13, participants who were inflammatory bowel disease (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 standard of care (SOC) regimen selected by the investigator (in accordance with the protocol) and entered the MP for up to 52 weeks.
|
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.
|
|---|---|---|
|
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
|
|
OL Phase (13 Weeks)
Adverse Event
|
0
|
2
|
|
OL Phase (13 Weeks)
Withdrawal by Subject
|
2
|
1
|
|
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)
Withdrawal by Subject
|
4
|
4
|
|
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: 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)
Withdrawal by Subject
|
1
|
1
|
|
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
|
|
Monitoring Phase (Up to Week 52)
Withdrawal by Subject
|
1
|
1
|
|
Monitoring Phase (Up to Week 52)
Study Terminated By Sponsor
|
0
|
1
|
Baseline Characteristics
Study to Evaluate the Testicular Safety of Filgotinib in Adult Males With Moderately to Severely Active Inflammatory Bowel Disease
Baseline characteristics by cohort
| Measure |
Filgotinib
n=69 Participants
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.
|
Placebo
n=70 Participants
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.
|
Total
n=139 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
36 years
STANDARD_DEVIATION 8.5 • n=5 Participants
|
34 years
STANDARD_DEVIATION 8.4 • n=7 Participants
|
35 years
STANDARD_DEVIATION 8.5 • n=5 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
69 Participants
n=5 Participants
|
70 Participants
n=7 Participants
|
139 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Ethnicity · Not Hispanic or Latino
|
68 Participants
n=5 Participants
|
68 Participants
n=7 Participants
|
136 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Ethnicity · Hispanic or Latino
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Ethnicity · Not Permitted
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Race · American Indian or Alaska Native
|
2 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Race · Asian
|
37 Participants
n=5 Participants
|
38 Participants
n=7 Participants
|
75 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Race · Black or African American
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Race · White
|
29 Participants
n=5 Participants
|
31 Participants
n=7 Participants
|
60 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Race · Not Permitted
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Sperm Concentration
|
63.4 million sperm cells/milliliter (mL)
STANDARD_DEVIATION 34.34 • n=5 Participants
|
61.8 million sperm cells/milliliter (mL)
STANDARD_DEVIATION 34.96 • n=7 Participants
|
62.6 million sperm cells/milliliter (mL)
STANDARD_DEVIATION 34.53 • n=5 Participants
|
|
Total Sperm Count
|
190.6 million sperm cells/ejaculate
STANDARD_DEVIATION 107.08 • n=5 Participants
|
171.1 million sperm cells/ejaculate
STANDARD_DEVIATION 100.74 • n=7 Participants
|
180.8 million sperm cells/ejaculate
STANDARD_DEVIATION 104.02 • n=5 Participants
|
|
Sperm Total Motility
|
59.6 percentage of motile sperm
STANDARD_DEVIATION 11.33 • n=5 Participants
|
58.6 percentage of motile sperm
STANDARD_DEVIATION 10.94 • n=7 Participants
|
59.1 percentage of motile sperm
STANDARD_DEVIATION 11.11 • n=5 Participants
|
|
Ejaculate Volume
|
3.2 mL
STANDARD_DEVIATION 1.20 • n=5 Participants
|
3.0 mL
STANDARD_DEVIATION 1.48 • n=7 Participants
|
3.1 mL
STANDARD_DEVIATION 1.35 • n=5 Participants
|
|
Percent Normal Sperm Morphology
|
41 percentage of normal sperm
STANDARD_DEVIATION 6.4 • n=5 Participants
|
41 percentage of normal sperm
STANDARD_DEVIATION 5.5 • n=7 Participants
|
41 percentage of normal sperm
STANDARD_DEVIATION 6.0 • n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline to Week 13Population: 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.
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.
Outcome measures
| Measure |
Filgotinib
n=66 Participants
Participants received filgotinib 200 mg tablet, orally, once daily up to Week 13 in the DB phase (Part A).
|
Placebo
n=67 Participants
Participants received placebo (matched to filgotinib) tablet, orally, once daily up to Week 13 in the DB phase (Part A).
|
Placebo/DB Placebo (Responder)
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).
|
Placebo/OL Filgotinib (Nonresponder)
Participants received placebo (matched to filgotinib) tablet, orally, once daily up to Week 13 in the DB phase (Part A). 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.
|
|---|---|---|---|---|
|
Percentage of Participants With a ≥ 50% Decrease From Baseline in Sperm Concentration at Week 13
|
1.5 percentage of participants
|
9.0 percentage of participants
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline to Week 26Population: 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.
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.
Outcome measures
| Measure |
Filgotinib
n=40 Participants
Participants received filgotinib 200 mg tablet, orally, once daily up to Week 13 in the DB phase (Part A).
|
Placebo
n=21 Participants
Participants received placebo (matched to filgotinib) tablet, orally, once daily up to Week 13 in the DB phase (Part A).
|
Placebo/DB Placebo (Responder)
n=38 Participants
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).
|
Placebo/OL Filgotinib (Nonresponder)
n=17 Participants
Participants received placebo (matched to filgotinib) tablet, orally, once daily up to Week 13 in the DB phase (Part A). 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.
|
|---|---|---|---|---|
|
Percentage of Participants With a ≥ 50% Decrease From Baseline in Sperm Concentration at Week 26
|
5.0 percentage of participants
|
0 percentage of participants
|
7.9 percentage of participants
|
11.8 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline, Week 13Population: Participants in the Semen Analysis Set were analyzed.
The normal range for sperm total motility is ≥40%.
Outcome measures
| Measure |
Filgotinib
n=66 Participants
Participants received filgotinib 200 mg tablet, orally, once daily up to Week 13 in the DB phase (Part A).
|
Placebo
n=67 Participants
Participants received placebo (matched to filgotinib) tablet, orally, once daily up to Week 13 in the DB phase (Part A).
|
Placebo/DB Placebo (Responder)
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).
|
Placebo/OL Filgotinib (Nonresponder)
Participants received placebo (matched to filgotinib) tablet, orally, once daily up to Week 13 in the DB phase (Part A). 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.
|
|---|---|---|---|---|
|
Change From Baseline in Sperm Total Motility at Week 13
|
-0.3 percentage of motile sperms
Interval -1.6 to 1.7
|
0.4 percentage of motile sperms
Interval -1.3 to 1.5
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, Week 26Population: Participants in the Week 26 Semen Analysis Set with available data were analyzed.
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%.
Outcome measures
| Measure |
Filgotinib
n=40 Participants
Participants received filgotinib 200 mg tablet, orally, once daily up to Week 13 in the DB phase (Part A).
|
Placebo
n=21 Participants
Participants received placebo (matched to filgotinib) tablet, orally, once daily up to Week 13 in the DB phase (Part A).
|
Placebo/DB Placebo (Responder)
n=36 Participants
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).
|
Placebo/OL Filgotinib (Nonresponder)
n=17 Participants
Participants received placebo (matched to filgotinib) tablet, orally, once daily up to Week 13 in the DB phase (Part A). 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.
|
|---|---|---|---|---|
|
Change From Baseline in Sperm Total Motility at Week 26
|
-2.3 percentage of motile sperms
Interval -4.7 to -0.3
|
-1.5 percentage of motile sperms
Interval -5.8 to 2.6
|
0.0 percentage of motile sperms
Interval -3.4 to 2.4
|
0.8 percentage of motile sperms
Interval -7.3 to 5.8
|
SECONDARY outcome
Timeframe: Baseline, Week 13Population: Participants in the Semen Analysis Set were analyzed.
The normal range for total sperm count is ≥ 39 million sperm cells/ejaculate.
Outcome measures
| Measure |
Filgotinib
n=66 Participants
Participants received filgotinib 200 mg tablet, orally, once daily up to Week 13 in the DB phase (Part A).
|
Placebo
n=67 Participants
Participants received placebo (matched to filgotinib) tablet, orally, once daily up to Week 13 in the DB phase (Part A).
|
Placebo/DB Placebo (Responder)
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).
|
Placebo/OL Filgotinib (Nonresponder)
Participants received placebo (matched to filgotinib) tablet, orally, once daily up to Week 13 in the DB phase (Part A). 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.
|
|---|---|---|---|---|
|
Change From Baseline in Total Sperm Count at Week 13
|
-11.6 million sperm cells/ejaculate
Interval -19.8 to 9.7
|
-9.5 million sperm cells/ejaculate
Interval -23.8 to 0.6
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, Week 26Population: Participants in the Week 26 Semen Analysis Set with available data were analyzed.
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.
Outcome measures
| Measure |
Filgotinib
n=40 Participants
Participants received filgotinib 200 mg tablet, orally, once daily up to Week 13 in the DB phase (Part A).
|
Placebo
n=21 Participants
Participants received placebo (matched to filgotinib) tablet, orally, once daily up to Week 13 in the DB phase (Part A).
|
Placebo/DB Placebo (Responder)
n=38 Participants
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).
|
Placebo/OL Filgotinib (Nonresponder)
n=17 Participants
Participants received placebo (matched to filgotinib) tablet, orally, once daily up to Week 13 in the DB phase (Part A). 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.
|
|---|---|---|---|---|
|
Change From Baseline in Total Sperm Count at Week 26
|
2.0 million sperm cells/ejaculate
Interval -19.6 to 17.2
|
-4.6 million sperm cells/ejaculate
Interval -42.3 to 18.3
|
-4.1 million sperm cells/ejaculate
Interval -39.8 to 15.9
|
12.7 million sperm cells/ejaculate
Interval -61.4 to 40.8
|
SECONDARY outcome
Timeframe: Baseline, Week 13Population: Participants in the Semen Analysis Set were analyzed.
The normal range for sperm concentration is ≥15 million sperm cells/mL.
Outcome measures
| Measure |
Filgotinib
n=66 Participants
Participants received filgotinib 200 mg tablet, orally, once daily up to Week 13 in the DB phase (Part A).
|
Placebo
n=67 Participants
Participants received placebo (matched to filgotinib) tablet, orally, once daily up to Week 13 in the DB phase (Part A).
|
Placebo/DB Placebo (Responder)
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).
|
Placebo/OL Filgotinib (Nonresponder)
Participants received placebo (matched to filgotinib) tablet, orally, once daily up to Week 13 in the DB phase (Part A). 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.
|
|---|---|---|---|---|
|
Change From Baseline in Sperm Concentration at Week 13
|
1.0 million sperm cells/mL
Interval -2.2 to 3.9
|
0.7 million sperm cells/mL
Interval -2.7 to 1.7
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, Week 26Population: Participants in the Week 26 Semen Analysis Set with available data were analyzed.
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.
Outcome measures
| Measure |
Filgotinib
n=40 Participants
Participants received filgotinib 200 mg tablet, orally, once daily up to Week 13 in the DB phase (Part A).
|
Placebo
n=21 Participants
Participants received placebo (matched to filgotinib) tablet, orally, once daily up to Week 13 in the DB phase (Part A).
|
Placebo/DB Placebo (Responder)
n=38 Participants
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).
|
Placebo/OL Filgotinib (Nonresponder)
n=17 Participants
Participants received placebo (matched to filgotinib) tablet, orally, once daily up to Week 13 in the DB phase (Part A). 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.
|
|---|---|---|---|---|
|
Change From Baseline in Sperm Concentration at Week 26
|
1.2 million sperm cells/mL
Interval -3.2 to 10.8
|
-0.6 million sperm cells/mL
Interval -8.5 to 23.0
|
0.8 million sperm cells/mL
Interval -2.4 to 5.3
|
-3.7 million sperm cells/mL
Interval -11.1 to 15.7
|
SECONDARY outcome
Timeframe: Baseline, Week 13Population: Participants in the Semen Analysis Set were analyzed.
The normal range for ejaculate volume is ≥1.5 mL.
Outcome measures
| Measure |
Filgotinib
n=66 Participants
Participants received filgotinib 200 mg tablet, orally, once daily up to Week 13 in the DB phase (Part A).
|
Placebo
n=67 Participants
Participants received placebo (matched to filgotinib) tablet, orally, once daily up to Week 13 in the DB phase (Part A).
|
Placebo/DB Placebo (Responder)
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).
|
Placebo/OL Filgotinib (Nonresponder)
Participants received placebo (matched to filgotinib) tablet, orally, once daily up to Week 13 in the DB phase (Part A). 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.
|
|---|---|---|---|---|
|
Change From Baseline in Ejaculate Volume at Week 13
|
-0.2 mL
Interval -0.3 to 0.1
|
-0.1 mL
Interval -0.3 to 0.0
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, Week 26Population: Participants in the Week 26 Semen Analysis Set with available data were analyzed.
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.
Outcome measures
| Measure |
Filgotinib
n=40 Participants
Participants received filgotinib 200 mg tablet, orally, once daily up to Week 13 in the DB phase (Part A).
|
Placebo
n=21 Participants
Participants received placebo (matched to filgotinib) tablet, orally, once daily up to Week 13 in the DB phase (Part A).
|
Placebo/DB Placebo (Responder)
n=38 Participants
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).
|
Placebo/OL Filgotinib (Nonresponder)
n=17 Participants
Participants received placebo (matched to filgotinib) tablet, orally, once daily up to Week 13 in the DB phase (Part A). 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.
|
|---|---|---|---|---|
|
Change From Baseline in Ejaculate Volume at Week 26
|
0.0 mL
Interval -0.5 to 0.2
|
-0.3 mL
Interval -0.8 to 0.2
|
-0.2 mL
Interval -0.5 to 0.1
|
-0.1 mL
Interval -0.7 to 0.4
|
SECONDARY outcome
Timeframe: Baseline, Week 13Population: Participants in the Semen Analysis Set were analyzed.
The normal range for percent normal sperm morphology is ≥30% normal sperms.
Outcome measures
| Measure |
Filgotinib
n=66 Participants
Participants received filgotinib 200 mg tablet, orally, once daily up to Week 13 in the DB phase (Part A).
|
Placebo
n=67 Participants
Participants received placebo (matched to filgotinib) tablet, orally, once daily up to Week 13 in the DB phase (Part A).
|
Placebo/DB Placebo (Responder)
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).
|
Placebo/OL Filgotinib (Nonresponder)
Participants received placebo (matched to filgotinib) tablet, orally, once daily up to Week 13 in the DB phase (Part A). 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.
|
|---|---|---|---|---|
|
Change From Baseline in Percent Normal Sperm Morphology at Week 13
|
2 percentage of normal sperms
Interval -1.0 to 4.0
|
1 percentage of normal sperms
Interval -1.0 to 2.0
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, Week 26Population: Participants in the Week 26 Semen Analysis Set with available data were analyzed.
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.
Outcome measures
| Measure |
Filgotinib
n=40 Participants
Participants received filgotinib 200 mg tablet, orally, once daily up to Week 13 in the DB phase (Part A).
|
Placebo
n=21 Participants
Participants received placebo (matched to filgotinib) tablet, orally, once daily up to Week 13 in the DB phase (Part A).
|
Placebo/DB Placebo (Responder)
n=38 Participants
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).
|
Placebo/OL Filgotinib (Nonresponder)
n=17 Participants
Participants received placebo (matched to filgotinib) tablet, orally, once daily up to Week 13 in the DB phase (Part A). 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.
|
|---|---|---|---|---|
|
Change From Baseline in Percent Normal Sperm Morphology at Week 26
|
3 percentage of normal sperms
Interval 1.0 to 5.0
|
1 percentage of normal sperms
Interval -2.0 to 3.0
|
2 percentage of normal sperms
Interval -4.0 to 5.0
|
2 percentage of normal sperms
Interval -2.0 to 3.0
|
Adverse Events
Filgotinib
Serious events: 3 serious events
Other events: 47 other events
Deaths: 0 deaths
Placebo
Serious events: 2 serious events
Other events: 24 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Filgotinib
n=92 participants at risk
Participants received filgotinib 200 mg tablet, orally once daily (OD) up to Week 13 in DB phase (Part A). At Week 13, IBD responders, without meeting pre-specified sperm decrease thresholds, continued DB phase treatment up to Week 26 (Part B). 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 prespecified decrease threshold, entered the OL Phase, and received OL filgotinib 200 mg, tablet orally OD for up to Week 13 during the OL phase. At Week 26/OL Week 13, IBD responders and who had not experienced disease worsening, and whose sperm parameters did not meet prespecified decrease threshold, continued receiving the same study drug they were responding to, as part of LTE for up to 195 weeks. Participants who met prespecified sperm decrease threshold(s) discontinued study drug and switched to SOC regimen selected by investigator and entered the MP for up to 52 weeks.
|
Placebo
n=70 participants at risk
Participants received placebo (matched to filgotinib) tablet, orally OD up to Week 13 in DB phase (Part A). At Week 13, IBD responders, without meeting pre-specified sperm decrease thresholds, continued DB phase treatment up to Week 26 (Part B). 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 prespecified decrease threshold, entered the OL Phase, and received OL filgotinib 200 mg, tablet orally OD for up to Week 13 during the OL phase. At Week 26/OL Week 13, IBD responders and who had not experienced disease worsening, and whose sperm parameters did not meet prespecified decrease threshold, continued receiving the same study drug they were responding to, as part of LTE for up to 195 weeks. Participants who met prespecified sperm decrease threshold(s) discontinued study drug and switched to SOC regimen selected by investigator and entered the MP for up to 52 weeks.
|
|---|---|---|
|
Gastrointestinal disorders
Colitis ulcerative
|
1.1%
1/92 • From first dose up to Week 226
All on-treatment safety data during the study were reported under the treatment received at the onset of the event (As-treated set).
|
1.4%
1/70 • From first dose up to Week 226
All on-treatment safety data during the study were reported under the treatment received at the onset of the event (As-treated set).
|
|
Gastrointestinal disorders
Crohn's disease
|
1.1%
1/92 • From first dose up to Week 226
All on-treatment safety data during the study were reported under the treatment received at the onset of the event (As-treated set).
|
0.00%
0/70 • From first dose up to Week 226
All on-treatment safety data during the study were reported under the treatment received at the onset of the event (As-treated set).
|
|
Infections and infestations
COVID-19
|
0.00%
0/92 • From first dose up to Week 226
All on-treatment safety data during the study were reported under the treatment received at the onset of the event (As-treated set).
|
1.4%
1/70 • From first dose up to Week 226
All on-treatment safety data during the study were reported under the treatment received at the onset of the event (As-treated set).
|
|
Infections and infestations
Pneumonia
|
1.1%
1/92 • From first dose up to Week 226
All on-treatment safety data during the study were reported under the treatment received at the onset of the event (As-treated set).
|
0.00%
0/70 • From first dose up to Week 226
All on-treatment safety data during the study were reported under the treatment received at the onset of the event (As-treated set).
|
Other adverse events
| Measure |
Filgotinib
n=92 participants at risk
Participants received filgotinib 200 mg tablet, orally once daily (OD) up to Week 13 in DB phase (Part A). At Week 13, IBD responders, without meeting pre-specified sperm decrease thresholds, continued DB phase treatment up to Week 26 (Part B). 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 prespecified decrease threshold, entered the OL Phase, and received OL filgotinib 200 mg, tablet orally OD for up to Week 13 during the OL phase. At Week 26/OL Week 13, IBD responders and who had not experienced disease worsening, and whose sperm parameters did not meet prespecified decrease threshold, continued receiving the same study drug they were responding to, as part of LTE for up to 195 weeks. Participants who met prespecified sperm decrease threshold(s) discontinued study drug and switched to SOC regimen selected by investigator and entered the MP for up to 52 weeks.
|
Placebo
n=70 participants at risk
Participants received placebo (matched to filgotinib) tablet, orally OD up to Week 13 in DB phase (Part A). At Week 13, IBD responders, without meeting pre-specified sperm decrease thresholds, continued DB phase treatment up to Week 26 (Part B). 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 prespecified decrease threshold, entered the OL Phase, and received OL filgotinib 200 mg, tablet orally OD for up to Week 13 during the OL phase. At Week 26/OL Week 13, IBD responders and who had not experienced disease worsening, and whose sperm parameters did not meet prespecified decrease threshold, continued receiving the same study drug they were responding to, as part of LTE for up to 195 weeks. Participants who met prespecified sperm decrease threshold(s) discontinued study drug and switched to SOC regimen selected by investigator and entered the MP for up to 52 weeks.
|
|---|---|---|
|
Gastrointestinal disorders
Colitis ulcerative
|
15.2%
14/92 • From first dose up to Week 226
All on-treatment safety data during the study were reported under the treatment received at the onset of the event (As-treated set).
|
4.3%
3/70 • From first dose up to Week 226
All on-treatment safety data during the study were reported under the treatment received at the onset of the event (As-treated set).
|
|
Infections and infestations
Latent tuberculosis
|
5.4%
5/92 • From first dose up to Week 226
All on-treatment safety data during the study were reported under the treatment received at the onset of the event (As-treated set).
|
7.1%
5/70 • From first dose up to Week 226
All on-treatment safety data during the study were reported under the treatment received at the onset of the event (As-treated set).
|
|
Infections and infestations
Nasopharyngitis
|
18.5%
17/92 • From first dose up to Week 226
All on-treatment safety data during the study were reported under the treatment received at the onset of the event (As-treated set).
|
4.3%
3/70 • From first dose up to Week 226
All on-treatment safety data during the study were reported under the treatment received at the onset of the event (As-treated set).
|
|
Infections and infestations
COVID-19
|
9.8%
9/92 • From first dose up to Week 226
All on-treatment safety data during the study were reported under the treatment received at the onset of the event (As-treated set).
|
4.3%
3/70 • From first dose up to Week 226
All on-treatment safety data during the study were reported under the treatment received at the onset of the event (As-treated set).
|
|
Gastrointestinal disorders
Abdominal pain
|
3.3%
3/92 • From first dose up to Week 226
All on-treatment safety data during the study were reported under the treatment received at the onset of the event (As-treated set).
|
7.1%
5/70 • From first dose up to Week 226
All on-treatment safety data during the study were reported under the treatment received at the onset of the event (As-treated set).
|
|
Infections and infestations
Furuncle
|
1.1%
1/92 • From first dose up to Week 226
All on-treatment safety data during the study were reported under the treatment received at the onset of the event (As-treated set).
|
5.7%
4/70 • From first dose up to Week 226
All on-treatment safety data during the study were reported under the treatment received at the onset of the event (As-treated set).
|
|
Nervous system disorders
Headache
|
7.6%
7/92 • From first dose up to Week 226
All on-treatment safety data during the study were reported under the treatment received at the onset of the event (As-treated set).
|
0.00%
0/70 • From first dose up to Week 226
All on-treatment safety data during the study were reported under the treatment received at the onset of the event (As-treated set).
|
|
General disorders
Pyrexia
|
5.4%
5/92 • From first dose up to Week 226
All on-treatment safety data during the study were reported under the treatment received at the onset of the event (As-treated set).
|
5.7%
4/70 • From first dose up to Week 226
All on-treatment safety data during the study were reported under the treatment received at the onset of the event (As-treated set).
|
|
Gastrointestinal disorders
Gastritis
|
7.6%
7/92 • From first dose up to Week 226
All on-treatment safety data during the study were reported under the treatment received at the onset of the event (As-treated set).
|
1.4%
1/70 • From first dose up to Week 226
All on-treatment safety data during the study were reported under the treatment received at the onset of the event (As-treated set).
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The sponsor must review and approve any results of the study or abstracts for professional meetings prepared by the investigator(s). Published data must not compromise the objectives of the study. Data from individual study centers in multicenter studies must not be published separately.
- Publication restrictions are in place
Restriction type: OTHER