Cytomegalovirus Infections
Conditions
Brief summary
This observational study will compare spermatogenesis in male adult renal transplant recipients receiving valganciclovir versus untreated matched controls. Data will be collected from each participant for up to 52 weeks post transplant.
Interventions
DRUGValganciclovir
Participants will receive valganciclovir 900 milligrams (mg) orally once daily for up to a maximum of 200 days post-transplant.
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
20 Years to 50 Years
Healthy volunteers
No
Inclusion criteria
* First renal transplant * Participant eligible to receive valganciclovir prophylaxis as determined by the treating physician in accordance with the local approved product prescribing information (Cohort A only) or the participant is not expected to require any valganciclovir prophylaxis (Cohort B only) post-transplant * Participant has no history of known infertility * Participant is able and willing to provide semen samples * Participant agrees to utilize a barrier contraceptive throughout the study or for at least 90 days after cessation of valganciclovir treatment
Exclusion criteria
* Prior ganciclovir or valganciclovir within 3 months of enrollment * Organ transplant other than kidney * Participant has received an investigational new drug in the 3 months prior to transplant * Participant hs received an alkylating agent or other medications known to affect fertility/spermatogenesis * Participant is unlikely to be available for follow-up for the entire duration of the study (up to 52 weeks)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Sperm Density From Baseline to the End of Treatment (EOT) | Baseline, EOT (Week 28) | Sperm density was calculated based on the average of two semen samples. Change was calculated as the sperm density measured at post-baseline visit (EOT) minus (-) the sperm density measured at baseline for each participant. A negative change from baseline indicated a lower sperm density (worsening). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in TUNEL Score From EOT to End of FU | EOT (Week 28), end of FU (Week 52) | Sperm DNA fragmentation change (chromatin damage) was evaluated based on TUNEL score. Change was calculated as the TUNEL score measured at FU minus the TUNEL score measured at EOT for each participant. A negative change from EOT indicated a lower TUNEL score. TUNEL score represents percentage of sperm with fragmented DNA; total score ranged from 0% to 100%, higher score represents more fragmentation. |
| Change in Seminal Volume From Baseline to EOT and End of FU | Baseline, EOT (Week 28), end of FU (Week 52) | Seminal volume was calculated based on the average of two semen samples. Change was calculated as the seminal volume measured at post-baseline visit (EOT and FU) - the seminal volume measured at baseline for each participant. A negative change from baseline indicated a lower seminal volume (worsening). |
| Change in Seminal Volume From EOT to End FU | EOT (Week 28), end of FU (Week 52) | Seminal volume was calculated based on the average of two semen samples. Change was calculated as the seminal volume measured at FU - the seminal volume measured at EOT for each participant. A negative change from EOT indicated a lower seminal volume (worsening). |
| Change in Sperm Density From EOT to End of FU | EOT (Week 28), end of FU (Week 52) | Sperm density was calculated based on the average of two semen samples. Change was calculated as the sperm density measured at FU - the sperm density measured at EOT for each participant. A negative change from EOT indicated a lower sperm density (worsening). |
| Change in Sperm Density From Baseline to End of FU | Baseline, end of FU (Week 52) | Sperm density was calculated based on the average of two semen samples. Change was calculated as the sperm density measured at post-baseline visit (FU) - the sperm density measured at baseline for each participant. A negative change from baseline indicated a lower sperm density (worsening). |
| Change in Total Motility of Sperm From Baseline to EOT and End of FU | Baseline, EOT (Week 28), end of FU (Week 52) | Sperm motility was calculated based on the average of two semen samples. Percent was determined by the calculation of motile sperm/total sperm count. Change was calculated as the sperm motility measured at post-baseline visit (EOT and FU) - the sperm motility measured at baseline for each participant. A negative change from baseline indicated a lower sperm motility (worsening). |
| Change in Total Motility of Sperm From EOT to End of FU | EOT (Week 28), end of FU (Week 52) | Sperm motility was calculated based on the average of two semen samples. Percent was determined by the calculation of motile sperm/total sperm count. Change was calculated as the sperm motility measured at FU - the sperm motility measured at EOT for each participant. A negative change from EOT indicated a lower sperm motility (worsening). |
| Change in Sperm Morphology Evaluated as Percentage of Normal Sperm Cells From Baseline to EOT and End of FU | Baseline, EOT (Week 28), end of FU (Week 52) | Sperm morphology was evaluated based on the average of two semen samples. Change was calculated as the sperm morphology measured at post-baseline visit (EOT and FU) - the sperm morphology measured at baseline for each participant. A positive change from baseline indicated an improved sperm morphology. |
| Change in Sperm Morphology Evaluated as Percentage of Normal Sperm Cells From EOT to End of FU | EOT (Week 28), end of FU (Week 52) | Sperm morphology was evaluated based on the average of two semen samples. Change was calculated as the sperm morphology measured at FU - the sperm morphology measured at EOT for each participant. A positive change from EOT indicated an improved sperm morphology. |
| Change in Total Testosterone Level From Baseline to EOT and End of FU | Baseline, EOT (Week 28), end of FU (Week 52) | Testosterone level was calculated based on the average of two samples. Change was calculated as the testosterone level measured at post-baseline visit (EOT and FU) - the testosterone level measured at baseline for each participant. A negative change from baseline indicated a lower testosterone level. |
| Change in Total Testosterone Level From EOT to End of FU | EOT (Week 28), end of FU (Week 52) | Testosterone level was calculated based on the average of two samples. Change was calculated as the testosterone level measured at FU - the testosterone level measured at EOT for each participant. A negative change from EOT indicated a lower testosterone level. |
| Change in LH Level From Baseline to EOT and End of FU | Baseline, EOT (Week 28), end of FU (Week 52) | LH level was calculated based on the average of two samples. Change was calculated as the LH level measured at post-baseline visit (EOT and FU) - the LH level measured at baseline for each participant. A negative change from baseline indicated a lower LH level. |
| Change in Terminal Uridine Nick-End Labeling (TUNEL) Score From Baseline to EOT and End of Follow-up (FU) | Baseline, EOT (Week 28), end of FU (Week 52) | Sperm DNA fragmentation change (chromatin damage) was evaluated based on TUNEL score. Change was calculated as the TUNEL score measured at post-baseline visit (EOT and FU) minus the TUNEL score measured at baseline for each participant. A negative change from baseline indicated a lower TUNEL score. TUNEL score represents percentage of sperm with fragmented DNA; total score ranged from 0 percent (%) to 100%, higher score represents more fragmentation. |
| Change in FSH Level From Baseline to EOT and End of FU | Baseline, EOT (Week 28), end of FU (Week 52) | FSH level was calculated based on the average of two samples. Change was calculated as the FSH level measured at post-baseline visit (EOT and FU) - the FSH level measured at baseline for each participant. A negative change from baseline indicated a lower FSH level. |
| Change in FSH Level From EOT to End of FU | EOT (Week 28), end of FU (Week 52) | FSH level was calculated based on the average of two samples. Change was calculated as the FSH level measured at FU - the FSH level measured at EOT for each participant. A negative change from EOT indicated a lower FSH level. |
| Change in Prolactin Level From Baseline to EOT and End of FU | Baseline, EOT (Week 28), end of FU (Week 52) | Prolactin level was calculated based on the average of two samples. Change was calculated as the prolactin level measured at post-baseline visit (EOT and FU) - the prolactin level measured at baseline for each participant. A negative change from baseline indicated a lower prolactin level. |
| Change in Prolactin Level From EOT to End of FU | EOT (Week 28), end of FU (Week 52) | Prolactin level was calculated based on the average of two samples. Change was calculated as the prolactin level measured at FU - the prolactin level measured at EOT for each participant. A negative change from EOT indicated a lower prolactin level. |
| Change in Inhibin B Level From Baseline to EOT and End of FU | Baseline, EOT (Week 28), end of FU (Week 52) | Inhibin B level was calculated based on the average of two samples. Change was calculated as the inhibin B level measured at post-baseline visit (EOT and FU) - the inhibin B level measured at baseline for each participant. A negative change from baseline indicated a lower inhibin B level. |
| Change in Inhibin B Level From EOT to End of FU | EOT (Week 28), end of FU (Week 52) | Inhibin B level was calculated based on the average of two samples. Change was calculated as the inhibin B level measured at FU - the inhibin B level measured at EOT for each participant. A negative change from EOT indicated a lower inhibin B level. |
| Percentage of Participants With Abnormal Sperm Density (<20 Mil/mL) From Baseline to EOT and End of FU | Baseline, EOT (Week 28), end of FU (Week 52) | Abnormal sperm density was considered as sperm density less than (\<) 20 mil/mL. Change in abnormal to abnormal sperm density and normal to abnormal sperm density from baseline to EOT and end of FU was reported. |
| Percentage of Participants With Abnormal Sperm Density (<20 Mil/mL) From EOT to End of FU | EOT (Week 28), end of FU (Week 52) | Abnormal sperm density was considered as sperm density \<20 mil/mL. Change in abnormal to abnormal sperm density and normal to abnormal sperm density from EOT to end of FU was reported. |
| Percentage of Participants With Improved TUNEL Score From Baseline to EOT and End of FU | Baseline, EOT (Week 28), end of FU (Week 52) | Sperm DNA fragmentation change (chromatin damage) was evaluated based on TUNEL score. Participants who had a lower TUNEL score compared to the previous time point were considered as improved. |
| Percentage of Participants With Improved TUNEL Score From EOT to End of FU | EOT (Week 28), end of FU (Week 52) | Sperm DNA fragmentation change (chromatin damage) was evaluated based on TUNEL score. Participants who had a lower TUNEL score compared to the previous time point were considered as improved. |
| Percentage of Participants With Improved Sperm Density From Baseline to EOT and End of FU | Baseline, EOT (Week 28), end of FU (Week 52) | Participants who had higher sperm density compared with the previous visit were considered as improved. |
| Percentage of Participants With Improved Sperm Density From EOT to End of FU | EOT (Week 28), end of FU (Week 52) | Participants who had higher sperm density compared with the previous visit were considered as improved. |
| Change in LH Level From EOT to End of FU | EOT (Week 28), end of FU (Week 52) | LH level was calculated based on the average of two samples. Change was calculated as the LH level measured at FU - the LH level measured at EOT for each participant. A negative change from EOT indicated a lower LH level. |
Countries
Mexico, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cohort A: Partcipants Who Received Valganciclovir Participants with D+/R- CMV serology, who received valganciclovir prophylaxis according to the local prescribing information, were observed for spermatogenesis up to 52 weeks post-transplant. | 37 |
| Cohort B: Untreated Participants Participants with D-/R- CMV serology, who did not receive prophylaxis, were observed for spermatogenesis up to 52 weeks post-transplant. | 21 |
| Total | 58 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 0 | 1 |
| Overall Study | Inclusion/Exclusion not met | 1 | 0 |
| Overall Study | Lost to Follow-up | 1 | 4 |
| Overall Study | No end of study status | 3 | 0 |
| Overall Study | Other | 9 | 2 |
| Overall Study | Withdrawal by Subject | 2 | 1 |
Baseline characteristics
| Characteristic | Cohort B: Untreated Participants | Total | Cohort A: Partcipants Who Received Valganciclovir |
|---|---|---|---|
| Age, Continuous | 32.5 years STANDARD_DEVIATION 5.81 | 34.5 years STANDARD_DEVIATION 7.36 | 35.6 years STANDARD_DEVIATION 7.96 |
| Follicle Stimulating Hormone (FSH) Level | 8.6 units per liter (U/L) STANDARD_DEVIATION 6.61 | 9.9 units per liter (U/L) STANDARD_DEVIATION 6.72 | 10.8 units per liter (U/L) STANDARD_DEVIATION 6.77 |
| Inhibin B Level | 149.1 picograms per milliliter (pg/mL) STANDARD_DEVIATION 98.45 | 122.3 picograms per milliliter (pg/mL) STANDARD_DEVIATION 78.7 | 103.4 picograms per milliliter (pg/mL) STANDARD_DEVIATION 55.82 |
| Luteinizing Hormone (LH) Level | 6.8 milliunits per milliliter (mU/mL) STANDARD_DEVIATION 6.86 | 6.6 milliunits per milliliter (mU/mL) STANDARD_DEVIATION 4.76 | 6.4 milliunits per milliliter (mU/mL) STANDARD_DEVIATION 2.61 |
| Percentage of Normal Sperm Cells | 33.5 percentage of normal sperm cells STANDARD_DEVIATION 39.03 | 20.3 percentage of normal sperm cells STANDARD_DEVIATION 30.15 | 11.4 percentage of normal sperm cells STANDARD_DEVIATION 18.44 |
| Prolactin Level | 164.5 mU/mL STANDARD_DEVIATION 46.22 | 170.9 mU/mL STANDARD_DEVIATION 63.46 | 175.4 mU/mL STANDARD_DEVIATION 73.51 |
| Seminal Volume | 2.0 milliliters (mL) STANDARD_DEVIATION 1.37 | 2.2 milliliters (mL) STANDARD_DEVIATION 1.46 | 2.4 milliliters (mL) STANDARD_DEVIATION 1.51 |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 21 Participants | 58 Participants | 37 Participants |
| Sperm Density | 23.2 millions of sperm/milliliter (mil/mL) STANDARD_DEVIATION 24.9 | 21.9 millions of sperm/milliliter (mil/mL) STANDARD_DEVIATION 26.77 | 21.0 millions of sperm/milliliter (mil/mL) STANDARD_DEVIATION 28.33 |
| Terminal Uridine Nick-End Labeling (TUNEL) Score | 12.9 units on a scale STANDARD_DEVIATION 10.6 | 13.8 units on a scale STANDARD_DEVIATION 10.03 | 14.4 units on a scale STANDARD_DEVIATION 9.8 |
| Testosterone Level | 11.3 nanomoles per liter (nmol/L) STANDARD_DEVIATION 5.54 | 13.0 nanomoles per liter (nmol/L) STANDARD_DEVIATION 5.84 | 14.2 nanomoles per liter (nmol/L) STANDARD_DEVIATION 5.83 |
| Total Motility of Sperm | 36.3 percent motility STANDARD_DEVIATION 24.24 | 30.0 percent motility STANDARD_DEVIATION 22.42 | 25.8 percent motility STANDARD_DEVIATION 20.46 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 24 / 31 | 19 / 21 |
| serious Total, serious adverse events | 10 / 31 | 12 / 21 |
Outcome results
Primary
Change in Sperm Density From Baseline to the End of Treatment (EOT)
Sperm density was calculated based on the average of two semen samples. Change was calculated as the sperm density measured at post-baseline visit (EOT) minus (-) the sperm density measured at baseline for each participant. A negative change from baseline indicated a lower sperm density (worsening).
Time frame: Baseline, EOT (Week 28)
Population: Safety population. Overall number of participants analyzed=participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort A: Partcipants Who Received Valganciclovir | Change in Sperm Density From Baseline to the End of Treatment (EOT) | -9.770 mil/mL | Standard Error 9.0518 |
| Cohort B: Untreated Participants | Change in Sperm Density From Baseline to the End of Treatment (EOT) | 30.396 mil/mL | Standard Error 11.3044 |
p-value: 0.007595% CI: [-68.869, -11.463]Mixed Models Analysis
Secondary
Change in FSH Level From Baseline to EOT and End of FU
FSH level was calculated based on the average of two samples. Change was calculated as the FSH level measured at post-baseline visit (EOT and FU) - the FSH level measured at baseline for each participant. A negative change from baseline indicated a lower FSH level.
Time frame: Baseline, EOT (Week 28), end of FU (Week 52)
Population: Safety population. Overall number of participants analyzed=participants evaluable for this outcome measure. Number analyzed indicates number of participants evaluated for this outcome measure at specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort A: Partcipants Who Received Valganciclovir | Change in FSH Level From Baseline to EOT and End of FU | Change at EOT | 1.521 U/L | Standard Error 1.0033 |
| Cohort A: Partcipants Who Received Valganciclovir | Change in FSH Level From Baseline to EOT and End of FU | Change at end of FU | -2.905 U/L | Standard Error 0.4113 |
| Cohort B: Untreated Participants | Change in FSH Level From Baseline to EOT and End of FU | Change at EOT | -1.020 U/L | Standard Error 1.4072 |
| Cohort B: Untreated Participants | Change in FSH Level From Baseline to EOT and End of FU | Change at end of FU | -1.922 U/L | Standard Error 0.5369 |
p-value: 0.150595% CI: [-0.969, 6.052]Mixed Models Analysis
p-value: 0.153995% CI: [-2.352, 0.387]Mixed Models Analysis
Secondary
Change in FSH Level From EOT to End of FU
FSH level was calculated based on the average of two samples. Change was calculated as the FSH level measured at FU - the FSH level measured at EOT for each participant. A negative change from EOT indicated a lower FSH level.
Time frame: EOT (Week 28), end of FU (Week 52)
Population: Safety population. Overall number of participants analyzed=participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort A: Partcipants Who Received Valganciclovir | Change in FSH Level From EOT to End of FU | -3.462 U/L | Standard Error 0.5036 |
| Cohort B: Untreated Participants | Change in FSH Level From EOT to End of FU | -1.988 U/L | Standard Error 0.6141 |
p-value: 0.079895% CI: [-3.136, 0.188]Mixed Models Analysis
Secondary
Change in Inhibin B Level From Baseline to EOT and End of FU
Inhibin B level was calculated based on the average of two samples. Change was calculated as the inhibin B level measured at post-baseline visit (EOT and FU) - the inhibin B level measured at baseline for each participant. A negative change from baseline indicated a lower inhibin B level.
Time frame: Baseline, EOT (Week 28), end of FU (Week 52)
Population: Safety population. Overall number of participants analyzed=participants evaluable for this outcome measure. Number analyzed indicates number of participants evaluated for this outcome measure at specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort A: Partcipants Who Received Valganciclovir | Change in Inhibin B Level From Baseline to EOT and End of FU | Change at EOT | 5.075 pg/mL | Standard Error 7.3778 |
| Cohort A: Partcipants Who Received Valganciclovir | Change in Inhibin B Level From Baseline to EOT and End of FU | Change at end of FU | 51.416 pg/mL | Standard Error 10.8658 |
| Cohort B: Untreated Participants | Change in Inhibin B Level From Baseline to EOT and End of FU | Change at EOT | -3.067 pg/mL | Standard Error 9.5924 |
| Cohort B: Untreated Participants | Change in Inhibin B Level From Baseline to EOT and End of FU | Change at end of FU | 10.734 pg/mL | Standard Error 13.9963 |
p-value: 0.500295% CI: [-16.223, 32.506]Mixed Models Analysis
p-value: 0.027995% CI: [4.72, 76.643]Mixed Models Analysis
Secondary
Change in Inhibin B Level From EOT to End of FU
Inhibin B level was calculated based on the average of two samples. Change was calculated as the inhibin B level measured at FU - the inhibin B level measured at EOT for each participant. A negative change from EOT indicated a lower inhibin B level.
Time frame: EOT (Week 28), end of FU (Week 52)
Population: Safety population. Overall number of participants analyzed=participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort A: Partcipants Who Received Valganciclovir | Change in Inhibin B Level From EOT to End of FU | 40.329 pg/mL | Standard Error 13.8221 |
| Cohort B: Untreated Participants | Change in Inhibin B Level From EOT to End of FU | 14.448 pg/mL | Standard Error 17.8932 |
p-value: 0.254895% CI: [-20.024, 71.786]Mixed Models Analysis
Secondary
Change in LH Level From Baseline to EOT and End of FU
LH level was calculated based on the average of two samples. Change was calculated as the LH level measured at post-baseline visit (EOT and FU) - the LH level measured at baseline for each participant. A negative change from baseline indicated a lower LH level.
Time frame: Baseline, EOT (Week 28), end of FU (Week 52)
Population: Safety population. Overall number of participants analyzed=participants evaluable for this outcome measure. Number analyzed indicates number of participants evaluated for this outcome measure at specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort A: Partcipants Who Received Valganciclovir | Change in LH Level From Baseline to EOT and End of FU | Change at EOT | -0.281 mU/mL | Standard Error 0.3743 |
| Cohort A: Partcipants Who Received Valganciclovir | Change in LH Level From Baseline to EOT and End of FU | Change at end of FU | -1.857 mU/mL | Standard Error 0.2787 |
| Cohort B: Untreated Participants | Change in LH Level From Baseline to EOT and End of FU | Change at EOT | -0.357 mU/mL | Standard Error 0.519 |
| Cohort B: Untreated Participants | Change in LH Level From Baseline to EOT and End of FU | Change at end of FU | -0.642 mU/mL | Standard Error 0.3635 |
p-value: 0.905395% CI: [-1.214, 1.366]Mixed Models Analysis
p-value: 0.010495% CI: [-2.125, -0.305]Mixed Models Analysis
Secondary
Change in LH Level From EOT to End of FU
LH level was calculated based on the average of two samples. Change was calculated as the LH level measured at FU - the LH level measured at EOT for each participant. A negative change from EOT indicated a lower LH level.
Time frame: EOT (Week 28), end of FU (Week 52)
Population: Safety population. Overall number of participants analyzed=participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort A: Partcipants Who Received Valganciclovir | Change in LH Level From EOT to End of FU | -1.482 mU/mL | Standard Error 0.2607 |
| Cohort B: Untreated Participants | Change in LH Level From EOT to End of FU | -0.417 mU/mL | Standard Error 0.3207 |
p-value: 0.014395% CI: [-1.899, -0.231]Mixed Models Analysis
Secondary
Change in Prolactin Level From Baseline to EOT and End of FU
Prolactin level was calculated based on the average of two samples. Change was calculated as the prolactin level measured at post-baseline visit (EOT and FU) - the prolactin level measured at baseline for each participant. A negative change from baseline indicated a lower prolactin level.
Time frame: Baseline, EOT (Week 28), end of FU (Week 52)
Population: Safety population. Overall number of participants analyzed=participants evaluable for this outcome measure. Number analyzed indicates number of participants evaluated for this outcome measure at specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort A: Partcipants Who Received Valganciclovir | Change in Prolactin Level From Baseline to EOT and End of FU | Change at EOT | 15.590 mU/mL | Standard Error 14.4761 |
| Cohort A: Partcipants Who Received Valganciclovir | Change in Prolactin Level From Baseline to EOT and End of FU | Change at end of FU | 9.829 mU/mL | Standard Error 13.1691 |
| Cohort B: Untreated Participants | Change in Prolactin Level From Baseline to EOT and End of FU | Change at EOT | 15.693 mU/mL | Standard Error 19.2663 |
| Cohort B: Untreated Participants | Change in Prolactin Level From Baseline to EOT and End of FU | Change at end of FU | -5.443 mU/mL | Standard Error 16.7203 |
p-value: 0.996595% CI: [-47.792, 47.585]Mixed Models Analysis
p-value: 0.463695% CI: [-26.599, 57.142]Mixed Models Analysis
Secondary
Change in Prolactin Level From EOT to End of FU
Prolactin level was calculated based on the average of two samples. Change was calculated as the prolactin level measured at FU - the prolactin level measured at EOT for each participant. A negative change from EOT indicated a lower prolactin level.
Time frame: EOT (Week 28), end of FU (Week 52)
Population: Safety population. Overall number of participants analyzed=participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort A: Partcipants Who Received Valganciclovir | Change in Prolactin Level From EOT to End of FU | -7.429 mU/mL | Standard Error 10.9988 |
| Cohort B: Untreated Participants | Change in Prolactin Level From EOT to End of FU | -16.169 mU/mL | Standard Error 13.5322 |
p-value: 0.613495% CI: [-26.438, 43.917]Mixed Models Analysis
Secondary
Change in Seminal Volume From Baseline to EOT and End of FU
Seminal volume was calculated based on the average of two semen samples. Change was calculated as the seminal volume measured at post-baseline visit (EOT and FU) - the seminal volume measured at baseline for each participant. A negative change from baseline indicated a lower seminal volume (worsening).
Time frame: Baseline, EOT (Week 28), end of FU (Week 52)
Population: Safety population. Overall number of participants analyzed=participants evaluable for this outcome measure. Number analyzed indicates number of participants evaluated for this outcome measure at specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort A: Partcipants Who Received Valganciclovir | Change in Seminal Volume From Baseline to EOT and End of FU | Change at EOT | -0.193 mL | Standard Error 0.2324 |
| Cohort A: Partcipants Who Received Valganciclovir | Change in Seminal Volume From Baseline to EOT and End of FU | Change at end of FU | -0.289 mL | Standard Error 0.2066 |
| Cohort B: Untreated Participants | Change in Seminal Volume From Baseline to EOT and End of FU | Change at EOT | -0.347 mL | Standard Error 0.2967 |
| Cohort B: Untreated Participants | Change in Seminal Volume From Baseline to EOT and End of FU | Change at end of FU | -0.161 mL | Standard Error 0.2685 |
p-value: 0.677395% CI: [-0.594, 0.903]Mixed Models Analysis
p-value: 0.704695% CI: [-0.806, 0.551]Mixed Models Analysis
Secondary
Change in Seminal Volume From EOT to End FU
Seminal volume was calculated based on the average of two semen samples. Change was calculated as the seminal volume measured at FU - the seminal volume measured at EOT for each participant. A negative change from EOT indicated a lower seminal volume (worsening).
Time frame: EOT (Week 28), end of FU (Week 52)
Population: Safety population. Overall number of participants analyzed=participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort A: Partcipants Who Received Valganciclovir | Change in Seminal Volume From EOT to End FU | -0.103 mL | Standard Error 0.2187 |
| Cohort B: Untreated Participants | Change in Seminal Volume From EOT to End FU | 0.024 mL | Standard Error 0.3067 |
p-value: 0.732395% CI: [-0.888, 0.633]Mixed Models Analysis
Secondary
Change in Sperm Density From Baseline to End of FU
Sperm density was calculated based on the average of two semen samples. Change was calculated as the sperm density measured at post-baseline visit (FU) - the sperm density measured at baseline for each participant. A negative change from baseline indicated a lower sperm density (worsening).
Time frame: Baseline, end of FU (Week 52)
Population: Safety population. Overall number of participants analyzed=participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort A: Partcipants Who Received Valganciclovir | Change in Sperm Density From Baseline to End of FU | 39.671 mil/mL | Standard Error 11.6679 |
| Cohort B: Untreated Participants | Change in Sperm Density From Baseline to End of FU | 49.866 mil/mL | Standard Error 15.8282 |
p-value: 0.605895% CI: [-49.934, 29.543]Mixed Models Analysis
Secondary
Change in Sperm Density From EOT to End of FU
Sperm density was calculated based on the average of two semen samples. Change was calculated as the sperm density measured at FU - the sperm density measured at EOT for each participant. A negative change from EOT indicated a lower sperm density (worsening).
Time frame: EOT (Week 28), end of FU (Week 52)
Population: Safety population. Overall number of participants analyzed=participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort A: Partcipants Who Received Valganciclovir | Change in Sperm Density From EOT to End of FU | 57.149 mil/mL | Standard Error 17.7736 |
| Cohort B: Untreated Participants | Change in Sperm Density From EOT to End of FU | 5.882 mil/mL | Standard Error 27.4837 |
p-value: 0.175695% CI: [-24.626, 127.159]Mixed Models Analysis
Secondary
Change in Sperm Morphology Evaluated as Percentage of Normal Sperm Cells From Baseline to EOT and End of FU
Sperm morphology was evaluated based on the average of two semen samples. Change was calculated as the sperm morphology measured at post-baseline visit (EOT and FU) - the sperm morphology measured at baseline for each participant. A positive change from baseline indicated an improved sperm morphology.
Time frame: Baseline, EOT (Week 28), end of FU (Week 52)
Population: Safety population. Overall number of participants analyzed=participants evaluable for this outcome measure. Number analyzed indicates number of participants evaluated for this outcome measure at specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort A: Partcipants Who Received Valganciclovir | Change in Sperm Morphology Evaluated as Percentage of Normal Sperm Cells From Baseline to EOT and End of FU | Change at EOT | 3.720 percentage of normal sperm cells | Standard Error 4.0233 |
| Cohort A: Partcipants Who Received Valganciclovir | Change in Sperm Morphology Evaluated as Percentage of Normal Sperm Cells From Baseline to EOT and End of FU | Change at end of FU | 5.128 percentage of normal sperm cells | Standard Error 2.8907 |
| Cohort B: Untreated Participants | Change in Sperm Morphology Evaluated as Percentage of Normal Sperm Cells From Baseline to EOT and End of FU | Change at EOT | 9.461 percentage of normal sperm cells | Standard Error 5.2737 |
| Cohort B: Untreated Participants | Change in Sperm Morphology Evaluated as Percentage of Normal Sperm Cells From Baseline to EOT and End of FU | Change at end of FU | 6.982 percentage of normal sperm cells | Standard Error 4.206 |
p-value: 0.402195% CI: [-19.524, 8.042]Mixed Models Analysis
p-value: 0.722995% CI: [-12.423, 8.714]Mixed Models Analysis
Secondary
Change in Sperm Morphology Evaluated as Percentage of Normal Sperm Cells From EOT to End of FU
Sperm morphology was evaluated based on the average of two semen samples. Change was calculated as the sperm morphology measured at FU - the sperm morphology measured at EOT for each participant. A positive change from EOT indicated an improved sperm morphology.
Time frame: EOT (Week 28), end of FU (Week 52)
Population: Safety population. Overall number of participants analyzed=participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort A: Partcipants Who Received Valganciclovir | Change in Sperm Morphology Evaluated as Percentage of Normal Sperm Cells From EOT to End of FU | -0.714 percentage of normal sperm cells | Standard Error 4.342 |
| Cohort B: Untreated Participants | Change in Sperm Morphology Evaluated as Percentage of Normal Sperm Cells From EOT to End of FU | 2.236 percentage of normal sperm cells | Standard Error 5.8507 |
p-value: 0.70895% CI: [-19.192, 13.291]Mixed Models Analysis
Secondary
Change in Terminal Uridine Nick-End Labeling (TUNEL) Score From Baseline to EOT and End of Follow-up (FU)
Sperm DNA fragmentation change (chromatin damage) was evaluated based on TUNEL score. Change was calculated as the TUNEL score measured at post-baseline visit (EOT and FU) minus the TUNEL score measured at baseline for each participant. A negative change from baseline indicated a lower TUNEL score. TUNEL score represents percentage of sperm with fragmented DNA; total score ranged from 0 percent (%) to 100%, higher score represents more fragmentation.
Time frame: Baseline, EOT (Week 28), end of FU (Week 52)
Population: Safety population. Overall number of participants analyzed=participants evaluable for this outcome measure. Number analyzed indicates number of participants evaluated for this outcome measure at specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort A: Partcipants Who Received Valganciclovir | Change in Terminal Uridine Nick-End Labeling (TUNEL) Score From Baseline to EOT and End of Follow-up (FU) | Change at EOT | -3.595 percent score | Standard Error 1.772 |
| Cohort A: Partcipants Who Received Valganciclovir | Change in Terminal Uridine Nick-End Labeling (TUNEL) Score From Baseline to EOT and End of Follow-up (FU) | Change at end of FU | -4.516 percent score | Standard Error 1.9542 |
| Cohort B: Untreated Participants | Change in Terminal Uridine Nick-End Labeling (TUNEL) Score From Baseline to EOT and End of Follow-up (FU) | Change at EOT | -5.354 percent score | Standard Error 2.068 |
| Cohort B: Untreated Participants | Change in Terminal Uridine Nick-End Labeling (TUNEL) Score From Baseline to EOT and End of Follow-up (FU) | Change at end of FU | -3.465 percent score | Standard Error 2.5475 |
p-value: 0.510995% CI: [-3.619, 7.135]Mixed Models Analysis
p-value: 0.744995% CI: [-7.566, 5.464]Mixed Models Analysis
Secondary
Change in Total Motility of Sperm From Baseline to EOT and End of FU
Sperm motility was calculated based on the average of two semen samples. Percent was determined by the calculation of motile sperm/total sperm count. Change was calculated as the sperm motility measured at post-baseline visit (EOT and FU) - the sperm motility measured at baseline for each participant. A negative change from baseline indicated a lower sperm motility (worsening).
Time frame: Baseline, EOT (Week 28), end of FU (Week 52)
Population: Safety population. Overall number of participants analyzed=participants evaluable for this outcome measure. Number analyzed indicates number of participants evaluated for this outcome measure at specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort A: Partcipants Who Received Valganciclovir | Change in Total Motility of Sperm From Baseline to EOT and End of FU | Change at EOT | 3.839 percent motility | Standard Error 5.4259 |
| Cohort A: Partcipants Who Received Valganciclovir | Change in Total Motility of Sperm From Baseline to EOT and End of FU | Change at FU | 24.736 percent motility | Standard Error 4.792 |
| Cohort B: Untreated Participants | Change in Total Motility of Sperm From Baseline to EOT and End of FU | Change at EOT | 25.667 percent motility | Standard Error 6.9723 |
| Cohort B: Untreated Participants | Change in Total Motility of Sperm From Baseline to EOT and End of FU | Change at FU | 34.538 percent motility | Standard Error 6.6024 |
p-value: 0.022295% CI: [-40.346, -3.311]Mixed Models Analysis
p-value: 0.249595% CI: [-26.795, 7.19]Mixed Models Analysis
Secondary
Change in Total Motility of Sperm From EOT to End of FU
Sperm motility was calculated based on the average of two semen samples. Percent was determined by the calculation of motile sperm/total sperm count. Change was calculated as the sperm motility measured at FU - the sperm motility measured at EOT for each participant. A negative change from EOT indicated a lower sperm motility (worsening).
Time frame: EOT (Week 28), end of FU (Week 52)
Population: Safety population. Overall number of participants analyzed=participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort A: Partcipants Who Received Valganciclovir | Change in Total Motility of Sperm From EOT to End of FU | 8.953 percent motility | Standard Error 6.3968 |
| Cohort B: Untreated Participants | Change in Total Motility of Sperm From EOT to End of FU | 20.635 percent motility | Standard Error 9.0663 |
p-value: 0.350595% CI: [-37.039, 13.674]Mixed Models Analysis
Secondary
Change in Total Testosterone Level From Baseline to EOT and End of FU
Testosterone level was calculated based on the average of two samples. Change was calculated as the testosterone level measured at post-baseline visit (EOT and FU) - the testosterone level measured at baseline for each participant. A negative change from baseline indicated a lower testosterone level.
Time frame: Baseline, EOT (Week 28), end of FU (Week 52)
Population: Safety population. Overall number of participants analyzed=participants evaluable for this outcome measure. Number analyzed indicates number of participants evaluated for this outcome measure at specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort A: Partcipants Who Received Valganciclovir | Change in Total Testosterone Level From Baseline to EOT and End of FU | Change at EOT | 0.762 nmol/L | Standard Error 1.0203 |
| Cohort A: Partcipants Who Received Valganciclovir | Change in Total Testosterone Level From Baseline to EOT and End of FU | Change at end of FU | 0.395 nmol/L | Standard Error 1.026 |
| Cohort B: Untreated Participants | Change in Total Testosterone Level From Baseline to EOT and End of FU | Change at EOT | 2.623 nmol/L | Standard Error 1.3586 |
| Cohort B: Untreated Participants | Change in Total Testosterone Level From Baseline to EOT and End of FU | Change at end of FU | 1.509 nmol/L | Standard Error 1.3074 |
p-value: 0.267395% CI: [-5.213, 1.491]Mixed Models Analysis
p-value: 0.494995% CI: [-4.392, 2.164]Mixed Models Analysis
Secondary
Change in Total Testosterone Level From EOT to End of FU
Testosterone level was calculated based on the average of two samples. Change was calculated as the testosterone level measured at FU - the testosterone level measured at EOT for each participant. A negative change from EOT indicated a lower testosterone level.
Time frame: EOT (Week 28), end of FU (Week 52)
Population: Safety population. Overall number of participants analyzed=participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort A: Partcipants Who Received Valganciclovir | Change in Total Testosterone Level From EOT to End of FU | -0.936 nmol/L | Standard Error 0.995 |
| Cohort B: Untreated Participants | Change in Total Testosterone Level From EOT to End of FU | -0.984 nmol/L | Standard Error 1.2012 |
p-value: 0.975395% CI: [-3.063, 3.157]Mixed Models Analysis
Secondary
Change in TUNEL Score From EOT to End of FU
Sperm DNA fragmentation change (chromatin damage) was evaluated based on TUNEL score. Change was calculated as the TUNEL score measured at FU minus the TUNEL score measured at EOT for each participant. A negative change from EOT indicated a lower TUNEL score. TUNEL score represents percentage of sperm with fragmented DNA; total score ranged from 0% to 100%, higher score represents more fragmentation.
Time frame: EOT (Week 28), end of FU (Week 52)
Population: Safety population. Overall number of participants analyzed=participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort A: Partcipants Who Received Valganciclovir | Change in TUNEL Score From EOT to End of FU | 4.447 percent score | Standard Error 2.0671 |
| Cohort B: Untreated Participants | Change in TUNEL Score From EOT to End of FU | 1.578 percent score | Standard Error 2.5315 |
p-value: 0.39495% CI: [-4.001, 9.739]Mixed Models Analysis
Secondary
Percentage of Participants With Abnormal Sperm Density (<20 Mil/mL) From Baseline to EOT and End of FU
Abnormal sperm density was considered as sperm density less than (\<) 20 mil/mL. Change in abnormal to abnormal sperm density and normal to abnormal sperm density from baseline to EOT and end of FU was reported.
Time frame: Baseline, EOT (Week 28), end of FU (Week 52)
Population: Safety population. Overall number of participants analyzed=participants evaluable for this outcome measure. Number analyzed indicates number of participants evaluated for this outcome measure at specified timepoint.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort A: Partcipants Who Received Valganciclovir | Percentage of Participants With Abnormal Sperm Density (<20 Mil/mL) From Baseline to EOT and End of FU | Abnormal to abnormal: EOT | 50.0 percentage of participants |
| Cohort A: Partcipants Who Received Valganciclovir | Percentage of Participants With Abnormal Sperm Density (<20 Mil/mL) From Baseline to EOT and End of FU | Abnormal to abnormal: FU | 25.0 percentage of participants |
| Cohort A: Partcipants Who Received Valganciclovir | Percentage of Participants With Abnormal Sperm Density (<20 Mil/mL) From Baseline to EOT and End of FU | Normal to abnormal: EOT | 25.0 percentage of participants |
| Cohort A: Partcipants Who Received Valganciclovir | Percentage of Participants With Abnormal Sperm Density (<20 Mil/mL) From Baseline to EOT and End of FU | Normal to abnormal: FU | 0.0 percentage of participants |
| Cohort B: Untreated Participants | Percentage of Participants With Abnormal Sperm Density (<20 Mil/mL) From Baseline to EOT and End of FU | Normal to abnormal: FU | 0.0 percentage of participants |
| Cohort B: Untreated Participants | Percentage of Participants With Abnormal Sperm Density (<20 Mil/mL) From Baseline to EOT and End of FU | Abnormal to abnormal: EOT | 35.7 percentage of participants |
| Cohort B: Untreated Participants | Percentage of Participants With Abnormal Sperm Density (<20 Mil/mL) From Baseline to EOT and End of FU | Normal to abnormal: EOT | 7.1 percentage of participants |
| Cohort B: Untreated Participants | Percentage of Participants With Abnormal Sperm Density (<20 Mil/mL) From Baseline to EOT and End of FU | Abnormal to abnormal: FU | 20.0 percentage of participants |
95% CI: [-19.3, 45.3]
95% CI: [-34.3, 43.3]
95% CI: [-15.3, 48.8]
Secondary
Percentage of Participants With Abnormal Sperm Density (<20 Mil/mL) From EOT to End of FU
Abnormal sperm density was considered as sperm density \<20 mil/mL. Change in abnormal to abnormal sperm density and normal to abnormal sperm density from EOT to end of FU was reported.
Time frame: EOT (Week 28), end of FU (Week 52)
Population: Safety population. Overall number of participants analyzed=participants evaluable for this outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort A: Partcipants Who Received Valganciclovir | Percentage of Participants With Abnormal Sperm Density (<20 Mil/mL) From EOT to End of FU | Abnormal to abnormal | 26.3 percentage of participants |
| Cohort A: Partcipants Who Received Valganciclovir | Percentage of Participants With Abnormal Sperm Density (<20 Mil/mL) From EOT to End of FU | Normal to abnormal | 0.0 percentage of participants |
| Cohort B: Untreated Participants | Percentage of Participants With Abnormal Sperm Density (<20 Mil/mL) From EOT to End of FU | Abnormal to abnormal | 22.2 percentage of participants |
| Cohort B: Untreated Participants | Percentage of Participants With Abnormal Sperm Density (<20 Mil/mL) From EOT to End of FU | Normal to abnormal | 0.0 percentage of participants |
95% CI: [-34.5, 42.5]
Secondary
Percentage of Participants With Improved Sperm Density From Baseline to EOT and End of FU
Participants who had higher sperm density compared with the previous visit were considered as improved.
Time frame: Baseline, EOT (Week 28), end of FU (Week 52)
Population: Safety population. Overall number of participants analyzed=participants evaluable for this outcome measure. Number analyzed indicates number of participants evaluated for this outcome measure at specified timepoint.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort A: Partcipants Who Received Valganciclovir | Percentage of Participants With Improved Sperm Density From Baseline to EOT and End of FU | EOT | 33.3 percentage of participants |
| Cohort A: Partcipants Who Received Valganciclovir | Percentage of Participants With Improved Sperm Density From Baseline to EOT and End of FU | FU | 90.0 percentage of participants |
| Cohort B: Untreated Participants | Percentage of Participants With Improved Sperm Density From Baseline to EOT and End of FU | EOT | 64.3 percentage of participants |
| Cohort B: Untreated Participants | Percentage of Participants With Improved Sperm Density From Baseline to EOT and End of FU | FU | 80.0 percentage of participants |
95% CI: [-59.7, 2.7]
95% CI: [-29.7, 47.7]
Secondary
Percentage of Participants With Improved Sperm Density From EOT to End of FU
Participants who had higher sperm density compared with the previous visit were considered as improved.
Time frame: EOT (Week 28), end of FU (Week 52)
Population: Safety population. Overall number of participants analyzed=participants evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort A: Partcipants Who Received Valganciclovir | Percentage of Participants With Improved Sperm Density From EOT to End of FU | 78.9 percentage of participants |
| Cohort B: Untreated Participants | Percentage of Participants With Improved Sperm Density From EOT to End of FU | 88.9 percentage of participants |
95% CI: [-47.2, 27.9]
Secondary
Percentage of Participants With Improved TUNEL Score From Baseline to EOT and End of FU
Sperm DNA fragmentation change (chromatin damage) was evaluated based on TUNEL score. Participants who had a lower TUNEL score compared to the previous time point were considered as improved.
Time frame: Baseline, EOT (Week 28), end of FU (Week 52)
Population: Safety population. Overall number of participants analyzed=participants evaluable for this outcome measure. Number analyzed indicates number of participants evaluated for this outcome measure at specified timepoint.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort A: Partcipants Who Received Valganciclovir | Percentage of Participants With Improved TUNEL Score From Baseline to EOT and End of FU | EOT | 72.7 percentage of participants |
| Cohort A: Partcipants Who Received Valganciclovir | Percentage of Participants With Improved TUNEL Score From Baseline to EOT and End of FU | FU | 66.7 percentage of participants |
| Cohort B: Untreated Participants | Percentage of Participants With Improved TUNEL Score From Baseline to EOT and End of FU | FU | 60.0 percentage of participants |
| Cohort B: Untreated Participants | Percentage of Participants With Improved TUNEL Score From Baseline to EOT and End of FU | EOT | 71.4 percentage of participants |
95% CI: [-31.3, 33.7]
95% CI: [-31.1, 44.4]
Secondary
Percentage of Participants With Improved TUNEL Score From EOT to End of FU
Sperm DNA fragmentation change (chromatin damage) was evaluated based on TUNEL score. Participants who had a lower TUNEL score compared to the previous time point were considered as improved.
Time frame: EOT (Week 28), end of FU (Week 52)
Population: Safety population. Overall number of participants analyzed=participants evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort A: Partcipants Who Received Valganciclovir | Percentage of Participants With Improved TUNEL Score From EOT to End of FU | 43.8 percentage of participants |
| Cohort B: Untreated Participants | Percentage of Participants With Improved TUNEL Score From EOT to End of FU | 55.6 percentage of participants |
95% CI: [-50, 29.3]