A Study on Spermatogenesis in Male Renal Transplant Recipients Receiving Valganciclovir (Valcyte®) Versus Untreated Matched Controls

Study Overview
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Brief Summary
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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.

Official Title
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A Multicenter Prospective Cohort Study to Investigate if Ganciclovir Significantly Affects Spermatogenesis in Adult Male Renal Transplant Recipients Receiving up to 200 Days Valganciclovir Vs. Concurrent Untreated Matched Controls

Conditions
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Cytomegalovirus Infections

Intervention / Treatment
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* Drug: Valganciclovir


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort A: Partcipants who Received Valganciclovir<br>Participants with donor positive (D+)/recipient negative (R-) cytomegalovirus (CMV) serology, who receive valganciclovir prophylaxis according to the local prescribing information, will be observed for spermatogenesis up to 52 weeks post-transplant. | Drug: Valganciclovir<br>* Participants will receive valganciclovir 900 milligrams (mg) orally once daily for up to a maximum of 200 days post-transplant.<br>* Other names: Valcyte®;|
| No Intervention: Cohort B: Untreated Participants<br>Participants with donor negative (D-)/R- CMV serology, who do not receive prophylaxis, will be observed for spermatogenesis up to 52 weeks post-transplant. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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). | Baseline, EOT (Week 28) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Baseline, EOT (Week 28), end of FU (Week 52) | 
| 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. | EOT (Week 28), end of FU (Week 52) | 
| 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). | Baseline, EOT (Week 28), end of FU (Week 52) | 
| 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). | EOT (Week 28), end of FU (Week 52) | 
| 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). | EOT (Week 28), end of FU (Week 52) | 
| 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). | Baseline, end of FU (Week 52) | 
| 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). | Baseline, EOT (Week 28), end of FU (Week 52) | 
| 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). | EOT (Week 28), end of FU (Week 52) | 
| 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. | Baseline, EOT (Week 28), end of FU (Week 52) | 
| 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. | EOT (Week 28), end of FU (Week 52) | 
| 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. | Baseline, EOT (Week 28), end of FU (Week 52) | 
| 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. | EOT (Week 28), end of FU (Week 52) | 
| 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. | Baseline, EOT (Week 28), end of FU (Week 52) | 
| 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. | EOT (Week 28), end of FU (Week 52) | 
| 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. | Baseline, EOT (Week 28), end of FU (Week 52) | 
| 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. | EOT (Week 28), end of FU (Week 52) | 
| 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. | Baseline, EOT (Week 28), end of FU (Week 52) | 
| 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. | EOT (Week 28), end of FU (Week 52) | 
| 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. | Baseline, EOT (Week 28), end of FU (Week 52) | 
| 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. | EOT (Week 28), end of FU (Week 52) | 
| 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. | Baseline, EOT (Week 28), end of FU (Week 52) | 
| 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. | EOT (Week 28), end of FU (Week 52) | 
| 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. | Baseline, EOT (Week 28), end of FU (Week 52) | 
| 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. | EOT (Week 28), end of FU (Week 52) | 
| 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. | Baseline, EOT (Week 28), end of FU (Week 52) | 
| 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. | EOT (Week 28), end of FU (Week 52) |