Ankylosing Spondylitis, Non-Radiographical Axial Spondyloarthritis, Psoriatic Arthritis, Rheumatoid Arthritis
Conditions
Brief summary
The primary objective of this study is to evaluate the effect of filgotinib on semen parameters in adult males with active rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, or non-radiographic axial spondyloarthritis. Results of this study may be pooled with the results of a separate study being conducted in participants with inflammatory bowel disease (Protocol GS-US-418-4279; NCT03201445) with the same objective.
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 rheumatic 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: * Diagnosis of active rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis or, non-radiographic axial spondyloarthritis for at least 12 weeks prior to screening, meeting the corresponding specific disease classification criteria as specified in the protocol Key
Exclusion criteria
* Previously documented problems with male reproductive health * Prior diagnosis of male infertility * Use of any prohibited concomitant medication 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 sperms/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 | Arthritis responder: For RA, PsA, AS, and nrAxSpA, a participant with an improvement in the PhGADA of at least 20% compared with baseline (Day 1) at the specified assessment time. Arthritis nonresponder: For RA, PsA, AS, or nrAxSpA, a participant who did not fulfill the definition of arthritis responder at the specified assessment timepoint. PhGADA: Physician measured the participant's disease severity on a VAS ranged from 0 (no disease)-100 (worst disease) mm. 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 sperms/ejaculate. |
| Change From Baseline in Total Sperm Count at Week 26 | Baseline, Week 26 | Arthritis responder: For RA, PsA, AS, and nrAxSpA, a participant with an improvement in the PhGADA of at least 20% compared with baseline (Day 1) at the specified assessment time. Arthritis nonresponder: For RA, PsA, AS, or nrAxSpA, a participant who did not fulfill the definition of arthritis responder at the specified assessment timepoint. PhGADA: Physician measured the participant's disease severity on a VAS ranged from 0 (no disease)-100 (worst disease) mm. The normal range for total sperm count is ≥ 39 million sperms/ejaculate. |
| Change From Baseline in Sperm Concentration at Week 13 | Baseline, Week 13 | The normal range for sperm concentration is ≥15 million sperms/mL. |
| Percentage of Participants With a ≥ 50% Decrease From Baseline in Sperm Concentration at Week 26 | Baseline to Week 26 | Arthritis responder: For rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), and non-radiographic axial spondyloarthritis (nrAxSpA), a participant with an improvement in the Physician's Global Assessment of Disease Activity (PhGADA) of at least 20% compared with baseline (Day 1) at the specified assessment time. Arthritis nonresponder: For RA, PsA, AS, or nrAxSpA, a participant who did not fulfill the definition of arthritis responder at the specified assessment timepoint. PhGADA: Physician measured the participant's disease severity on a visual analogue scale (VAS) ranged from 0 (no disease)-100 (worst disease) millimeters (mm). Baseline value for sperm/semen parameters was the mean of 2 evaluable semen collections at the screening visit. The normal range for sperm concentration is ≥15 million sperms/mL. Percentage change = (\[mean at Week 26 - baseline\] / baseline) × 100; value at Week 26 was the mean of 2 evaluable samples collected at Week 26. |
| 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 | Arthritis responder: For RA, PsA, AS, and nrAxSpA, a participant with an improvement in the PhGADA of at least 20% compared with baseline (Day 1) at the specified assessment time. Arthritis nonresponder: For RA, PsA, AS, or nrAxSpA, a participant who did not fulfill the definition of arthritis responder at the specified assessment timepoint. PhGADA: Physician measured the participant's disease severity on a VAS ranged from 0 (no disease)-100 (worst disease) mm. 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 | Arthritis responder: For RA, PsA, AS, and nrAxSpA, a participant with an improvement in the PhGADA of at least 20% compared with baseline (Day 1) at the specified assessment time. Arthritis nonresponder: For RA, PsA, AS, or nrAxSpA, a participant who did not fulfill the definition of arthritis responder at the specified assessment timepoint. PhGADA: Physician measured the participant's disease severity on a VAS ranged from 0 (no disease)-100 (worst disease) mm. The normal range for percent normal sperm morphology is ≥30% normal sperms. |
| Change From Baseline in Sperm Concentration at Week 26 | Baseline, Week 26 | Arthritis responder: For RA, PsA, AS, and nrAxSpA, a participant with an improvement in the PhGADA of at least 20% compared with baseline (Day 1) at the specified assessment time. Arthritis nonresponder: For RA, PsA, AS, or nrAxSpA, a participant who did not fulfill the definition of arthritis responder at the specified assessment timepoint. PhGADA: Physician measured the participant's disease severity on a VAS ranged from 0 (no disease)-100 (worst disease) mm. The normal range for sperm concentration is ≥15 million sperms/mL. |
Countries
Bulgaria, Czechia, Estonia, Georgia, Latvia, Poland, Spain, Ukraine
Participant flow
Recruitment details
Participants were enrolled at study sites in Bulgaria, Czech Republic, Estonia, Georgia, Latvia, Poland, Spain, and Ukraine. The first participant was screened on 28 May 2019. A total of 308 participants were screened of which 109 participants were randomized into the study.
Pre-assignment details
There were 3 distinct parts to the study: 1\) Double-Blind Treatment Phase (DB Phase; Day 1 through the Week 13 study visit); 2) Extension Phase (EXT Phase; after the Week 13 study visit and up to Week 156); and 3) Monitoring Phase (up to 52 weeks).
Participants by arm
| Arm | Count |
|---|---|
| Filgonitib Participants received filgotinib 200 mg tablet, orally, once daily up to Week 13 in the DB phase. At Week 13, participants who were arthritis responders, were unblinded and received OL treatment filgotinib 200 mg, tablet, orally, once daily up to approximately 143 weeks (until Week 156) in the EXT phase and participants who were arthritis nonresponders discontinued blinded study drug and started SOC treatment in the EXT phase. Participants on DB treatment or OL filgotinib who entered the monitoring phase (if their sperm parameters met ≥50% decrease threshold in pre-specified semen parameters) discontinued the study drug and started SOC for up to 52 weeks. | 54 |
| Placebo Participants received placebo (matched to filgotinib) tablet, orally, once daily up to Week 13 in the DB phase. At Week 13, participants were unblinded and started SOC treatment in the EXT phase for up to approximately 143 weeks (until Week 156). Participants who entered the monitoring phase (if their sperm parameters met ≥50% decrease threshold in pre-specified semen parameters) continued on SOC treatment. | 55 |
| Total | 109 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| DB Treatment Phase (Through Week 13) | Withdrawal by Subject | 0 | 2 |
| EXT Phase (Through Week 156) | Adverse Event | 5 | 1 |
| EXT Phase (Through Week 156) | Physician Decision | 0 | 2 |
| EXT Phase (Through Week 156) | Pre-Specified Decrease In Sperm Parameters | 16 | 17 |
| EXT Phase (Through Week 156) | Withdrawal by Subject | 1 | 3 |
| Monitoring Phase (52 Weeks) | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Placebo | Total | Filgonitib |
|---|---|---|---|
| Age, Continuous | 39 years STANDARD_DEVIATION 7.8 | 40 years STANDARD_DEVIATION 8.1 | 40 years STANDARD_DEVIATION 8.5 |
| Ejaculate Volume | 3.5 mL STANDARD_DEVIATION 1.29 | 3.3 mL STANDARD_DEVIATION 1.29 | 3.1 mL STANDARD_DEVIATION 1.26 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 55 Participants | 108 Participants | 53 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Percent Normal Sperm Morphology | 43 percentage of normal sperm STANDARD_DEVIATION 6 | 43 percentage of normal sperm STANDARD_DEVIATION 6 | 43 percentage of normal sperm STANDARD_DEVIATION 6.2 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 55 Participants | 109 Participants | 54 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 55 Participants | 109 Participants | 54 Participants |
| Sperm Concentration | 66.9 million sperms/milliliter (mL) STANDARD_DEVIATION 38.72 | 69.0 million sperms/milliliter (mL) STANDARD_DEVIATION 39.74 | 71.2 million sperms/milliliter (mL) STANDARD_DEVIATION 41 |
| Sperm Total Motility | 58.2 percentage of motile sperm STANDARD_DEVIATION 8.48 | 57.1 percentage of motile sperm STANDARD_DEVIATION 8.77 | 55.9 percentage of motile sperm STANDARD_DEVIATION 8.99 |
| Total Sperm Count | 225.2 million sperms/ejaculate STANDARD_DEVIATION 137.39 | 216.9 million sperms/ejaculate STANDARD_DEVIATION 136.79 | 208.4 million sperms/ejaculate STANDARD_DEVIATION 136.94 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 54 | 0 / 55 | 0 / 49 | 0 / 7 | 0 / 39 |
| other Total, other adverse events | 12 / 54 | 10 / 55 | 23 / 49 | 5 / 7 | 20 / 39 |
| serious Total, serious adverse events | 2 / 54 | 1 / 55 | 2 / 49 | 1 / 7 | 5 / 39 |
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 sperms/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) |
|---|---|---|
| Filgonitib | Percentage of Participants With a ≥ 50% Decrease From Baseline in Sperm Concentration at Week 13 | 13.0 percentage of participants |
| Placebo | Percentage of Participants With a ≥ 50% Decrease From Baseline in Sperm Concentration at Week 13 | 7.5 percentage of participants |
95% CI: [-7.5, 19.2]
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) |
|---|---|---|
| Filgonitib | Change From Baseline in Ejaculate Volume at Week 13 | -0.3 mL |
| Placebo | Change From Baseline in Ejaculate Volume at Week 13 | -0.2 mL |
95% CI: [-0.6, 0.1]
Secondary
Change From Baseline in Ejaculate Volume at Week 26
Arthritis responder: For RA, PsA, AS, and nrAxSpA, a participant with an improvement in the PhGADA of at least 20% compared with baseline (Day 1) at the specified assessment time. Arthritis nonresponder: For RA, PsA, AS, or nrAxSpA, a participant who did not fulfill the definition of arthritis responder at the specified assessment timepoint. PhGADA: Physician measured the participant's disease severity on a VAS ranged from 0 (no disease)-100 (worst disease) mm. The normal range for ejaculate volume is ≥1.5 mL.
Time frame: Baseline, Week 26
Population: Participants in the Week 26 Semen Analysis Set were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Filgonitib | Change From Baseline in Ejaculate Volume at Week 26 | -0.2 mL |
| Placebo | Change From Baseline in Ejaculate Volume at Week 26 | -0.6 mL |
| Filgotinib/SOC (Nonresponder) | Change From Baseline in Ejaculate Volume at Week 26 | 0.2 mL |
| Placebo/SOC (Nonresponder) | Change From Baseline in Ejaculate Volume at Week 26 | -0.3 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) |
|---|---|---|
| Filgonitib | Change From Baseline in Percent Normal Sperm Morphology at Week 13 | 1 percentage of normal sperms |
| Placebo | Change From Baseline in Percent Normal Sperm Morphology at Week 13 | 1 percentage of normal sperms |
95% CI: [-3, 1]
Secondary
Change From Baseline in Percent Normal Sperm Morphology at Week 26
Arthritis responder: For RA, PsA, AS, and nrAxSpA, a participant with an improvement in the PhGADA of at least 20% compared with baseline (Day 1) at the specified assessment time. Arthritis nonresponder: For RA, PsA, AS, or nrAxSpA, a participant who did not fulfill the definition of arthritis responder at the specified assessment timepoint. PhGADA: Physician measured the participant's disease severity on a VAS ranged from 0 (no disease)-100 (worst disease) mm. 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 were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Filgonitib | Change From Baseline in Percent Normal Sperm Morphology at Week 26 | 1 percentage of normal sperms |
| Placebo | Change From Baseline in Percent Normal Sperm Morphology at Week 26 | 3 percentage of normal sperms |
| Filgotinib/SOC (Nonresponder) | Change From Baseline in Percent Normal Sperm Morphology at Week 26 | 3 percentage of normal sperms |
| Placebo/SOC (Nonresponder) | Change From Baseline in Percent Normal Sperm Morphology at Week 26 | 4 percentage of normal sperms |
Secondary
Change From Baseline in Sperm Concentration at Week 13
The normal range for sperm concentration is ≥15 million sperms/mL.
Time frame: Baseline, Week 13
Population: Participants in the Semen Analysis Set were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Filgonitib | Change From Baseline in Sperm Concentration at Week 13 | 3.7 million sperms/mL |
| Placebo | Change From Baseline in Sperm Concentration at Week 13 | -0.4 million sperms/mL |
95% CI: [-6, 20.8]
Secondary
Change From Baseline in Sperm Concentration at Week 26
Arthritis responder: For RA, PsA, AS, and nrAxSpA, a participant with an improvement in the PhGADA of at least 20% compared with baseline (Day 1) at the specified assessment time. Arthritis nonresponder: For RA, PsA, AS, or nrAxSpA, a participant who did not fulfill the definition of arthritis responder at the specified assessment timepoint. PhGADA: Physician measured the participant's disease severity on a VAS ranged from 0 (no disease)-100 (worst disease) mm. The normal range for sperm concentration is ≥15 million sperms/mL.
Time frame: Baseline, Week 26
Population: Participants in the Week 26 Semen Analysis Set were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Filgonitib | Change From Baseline in Sperm Concentration at Week 26 | 1.7 million sperms/mL |
| Placebo | Change From Baseline in Sperm Concentration at Week 26 | 9.6 million sperms/mL |
| Filgotinib/SOC (Nonresponder) | Change From Baseline in Sperm Concentration at Week 26 | 10.3 million sperms/mL |
| Placebo/SOC (Nonresponder) | Change From Baseline in Sperm Concentration at Week 26 | -5.8 million sperms/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 with available data were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Filgonitib | Change From Baseline in Sperm Total Motility at Week 13 | -2.3 percentage of motile sperms |
| Placebo | Change From Baseline in Sperm Total Motility at Week 13 | -1.7 percentage of motile sperms |
95% CI: [-6.4, 3.5]
Secondary
Change From Baseline in Sperm Total Motility at Week 26
Arthritis responder: For RA, PsA, AS, and nrAxSpA, a participant with an improvement in the PhGADA of at least 20% compared with baseline (Day 1) at the specified assessment time. Arthritis nonresponder: For RA, PsA, AS, or nrAxSpA, a participant who did not fulfill the definition of arthritis responder at the specified assessment timepoint. PhGADA: Physician measured the participant's disease severity on a VAS ranged from 0 (no disease)-100 (worst disease) mm. 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) |
|---|---|---|
| Filgonitib | Change From Baseline in Sperm Total Motility at Week 26 | -2.4 percentage of motile sperms |
| Placebo | Change From Baseline in Sperm Total Motility at Week 26 | 0.9 percentage of motile sperms |
| Filgotinib/SOC (Nonresponder) | Change From Baseline in Sperm Total Motility at Week 26 | -1.4 percentage of motile sperms |
| Placebo/SOC (Nonresponder) | Change From Baseline in Sperm Total Motility at Week 26 | -2.8 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 sperms/ejaculate.
Time frame: Baseline, Week 13
Population: Participants in the Semen Analysis Set were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Filgonitib | Change From Baseline in Total Sperm Count at Week 13 | -2.1 million sperms/ejaculate |
| Placebo | Change From Baseline in Total Sperm Count at Week 13 | -9.6 million sperms/ejaculate |
95% CI: [-37.1, 36.8]
Secondary
Change From Baseline in Total Sperm Count at Week 26
Arthritis responder: For RA, PsA, AS, and nrAxSpA, a participant with an improvement in the PhGADA of at least 20% compared with baseline (Day 1) at the specified assessment time. Arthritis nonresponder: For RA, PsA, AS, or nrAxSpA, a participant who did not fulfill the definition of arthritis responder at the specified assessment timepoint. PhGADA: Physician measured the participant's disease severity on a VAS ranged from 0 (no disease)-100 (worst disease) mm. The normal range for total sperm count is ≥ 39 million sperms/ejaculate.
Time frame: Baseline, Week 26
Population: Participants in the Week 26 Semen Analysis Set were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Filgonitib | Change From Baseline in Total Sperm Count at Week 26 | -0.2 million sperms/ejaculate |
| Placebo | Change From Baseline in Total Sperm Count at Week 26 | 16.8 million sperms/ejaculate |
| Filgotinib/SOC (Nonresponder) | Change From Baseline in Total Sperm Count at Week 26 | 32.2 million sperms/ejaculate |
| Placebo/SOC (Nonresponder) | Change From Baseline in Total Sperm Count at Week 26 | -29.9 million sperms/ejaculate |
Secondary
Percentage of Participants With a ≥ 50% Decrease From Baseline in Sperm Concentration at Week 26
Arthritis responder: For rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), and non-radiographic axial spondyloarthritis (nrAxSpA), a participant with an improvement in the Physician's Global Assessment of Disease Activity (PhGADA) of at least 20% compared with baseline (Day 1) at the specified assessment time. Arthritis nonresponder: For RA, PsA, AS, or nrAxSpA, a participant who did not fulfill the definition of arthritis responder at the specified assessment timepoint. PhGADA: Physician measured the participant's disease severity on a visual analogue scale (VAS) ranged from 0 (no disease)-100 (worst disease) millimeters (mm). Baseline value for sperm/semen parameters was the mean of 2 evaluable semen collections at the screening visit. The normal range for sperm concentration is ≥15 million sperms/mL. Percentage change = (\[mean at Week 26 - baseline\] / baseline) × 100; value at Week 26 was the mean of 2 evaluable samples collected at Week 26.
Time frame: Baseline to Week 26
Population: The Week 26 Semen Analysis Set included all participants treated (≥ 1 dose of open-label filgotinib or SOC in the extension phase) who had 2 evaluable samples at baseline and at Week 26.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Filgonitib | Percentage of Participants With a ≥ 50% Decrease From Baseline in Sperm Concentration at Week 26 | 10.3 percentage of participants |
| Placebo | Percentage of Participants With a ≥ 50% Decrease From Baseline in Sperm Concentration at Week 26 | 8.0 percentage of participants |
| Filgotinib/SOC (Nonresponder) | Percentage of Participants With a ≥ 50% Decrease From Baseline in Sperm Concentration at Week 26 | 14.3 percentage of participants |
| Placebo/SOC (Nonresponder) | Percentage of Participants With a ≥ 50% Decrease From Baseline in Sperm Concentration at Week 26 | 0 percentage of participants |