Trial Outcomes & Findings for A Study on Spermatogenesis in Male Renal Transplant Recipients Receiving Valganciclovir (Valcyte®) Versus Untreated Matched Controls (NCT NCT01663740)

Last Updated: 2018-08-31

Results Overview

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).

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

59 participants

Primary outcome timeframe

Baseline, EOT (Week 28)

Results posted on

2018-08-31

Participant Flow

Participant milestones

Participant milestones
Measure	Cohort A: Partcipants Who Received Valganciclovir Participants with donor positive (D+)/recipient negative (R-) cytomegalovirus (CMV) serology, who received valganciclovir prophylaxis according to the local prescribing information, were observed for spermatogenesis up to 52 weeks post-transplant.	Cohort B: Untreated Participants Participants with donor negative (D-)/R- CMV serology, who did not receive prophylaxis, were observed for spermatogenesis up to 52 weeks post-transplant.
Overall Study STARTED	38	21
Overall Study COMPLETED	22	13
Overall Study NOT COMPLETED	16	8

Reasons for withdrawal

Reasons for withdrawal
Measure	Cohort A: Partcipants Who Received Valganciclovir Participants with donor positive (D+)/recipient negative (R-) cytomegalovirus (CMV) serology, who received valganciclovir prophylaxis according to the local prescribing information, were observed for spermatogenesis up to 52 weeks post-transplant.	Cohort B: Untreated Participants Participants with donor negative (D-)/R- CMV serology, who did not receive prophylaxis, were observed for spermatogenesis up to 52 weeks post-transplant.
Overall Study Lost to Follow-up	1	4
Overall Study Other	9	2
Overall Study Inclusion/Exclusion not met	1	0
Overall Study Death	0	1
Overall Study Withdrawal by Subject	2	1
Overall Study No end of study status	3	0

Baseline Characteristics

Number analyzed indicates number of participants evaluated for this analysis.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cohort A: Partcipants Who Received Valganciclovir n=37 Participants 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.	Cohort B: Untreated Participants n=21 Participants Participants with D-/R- CMV serology, who did not receive prophylaxis, were observed for spermatogenesis up to 52 weeks post-transplant.	Total n=58 Participants Total of all reporting groups
Age, Continuous	35.6 years STANDARD_DEVIATION 7.96 • n=37 Participants	32.5 years STANDARD_DEVIATION 5.81 • n=21 Participants	34.5 years STANDARD_DEVIATION 7.36 • n=58 Participants
Sex: Female, Male Female	0 Participants n=37 Participants	0 Participants n=21 Participants	0 Participants n=58 Participants
Sex: Female, Male Male	37 Participants n=37 Participants	21 Participants n=21 Participants	58 Participants n=58 Participants
Seminal Volume	2.4 milliliters (mL) STANDARD_DEVIATION 1.51 • n=30 Participants • Number analyzed indicates number of participants evaluated for this analysis.	2.0 milliliters (mL) STANDARD_DEVIATION 1.37 • n=20 Participants • Number analyzed indicates number of participants evaluated for this analysis.	2.2 milliliters (mL) STANDARD_DEVIATION 1.46 • n=50 Participants • Number analyzed indicates number of participants evaluated for this analysis.
Sperm Density	21.0 millions of sperm/milliliter (mil/mL) STANDARD_DEVIATION 28.33 • n=30 Participants • Number analyzed indicates number of participants evaluated for this analysis.	23.2 millions of sperm/milliliter (mil/mL) STANDARD_DEVIATION 24.90 • n=20 Participants • Number analyzed indicates number of participants evaluated for this analysis.	21.9 millions of sperm/milliliter (mil/mL) STANDARD_DEVIATION 26.77 • n=50 Participants • Number analyzed indicates number of participants evaluated for this analysis.
Percentage of Normal Sperm Cells	11.4 percentage of normal sperm cells STANDARD_DEVIATION 18.44 • n=27 Participants • Number analyzed indicates number of participants evaluated for this analysis.	33.5 percentage of normal sperm cells STANDARD_DEVIATION 39.03 • n=18 Participants • Number analyzed indicates number of participants evaluated for this analysis.	20.3 percentage of normal sperm cells STANDARD_DEVIATION 30.15 • n=45 Participants • Number analyzed indicates number of participants evaluated for this analysis.
Total Motility of Sperm	25.8 percent motility STANDARD_DEVIATION 20.46 • n=30 Participants • Number analyzed indicates number of participants evaluated for this analysis.	36.3 percent motility STANDARD_DEVIATION 24.24 • n=20 Participants • Number analyzed indicates number of participants evaluated for this analysis.	30.0 percent motility STANDARD_DEVIATION 22.42 • n=50 Participants • Number analyzed indicates number of participants evaluated for this analysis.
Terminal Uridine Nick-End Labeling (TUNEL) Score	14.4 units on a scale STANDARD_DEVIATION 9.80 • n=28 Participants • Number analyzed indicates number of participants evaluated for this analysis.	12.9 units on a scale STANDARD_DEVIATION 10.60 • n=18 Participants • Number analyzed indicates number of participants evaluated for this analysis.	13.8 units on a scale STANDARD_DEVIATION 10.03 • n=46 Participants • Number analyzed indicates number of participants evaluated for this analysis.
Follicle Stimulating Hormone (FSH) Level	10.8 units per liter (U/L) STANDARD_DEVIATION 6.77 • n=29 Participants • Number analyzed indicates number of participants evaluated for this analysis.	8.6 units per liter (U/L) STANDARD_DEVIATION 6.61 • n=20 Participants • Number analyzed indicates number of participants evaluated for this analysis.	9.9 units per liter (U/L) STANDARD_DEVIATION 6.72 • n=49 Participants • Number analyzed indicates number of participants evaluated for this analysis.
Luteinizing Hormone (LH) Level	6.4 milliunits per milliliter (mU/mL) STANDARD_DEVIATION 2.61 • n=29 Participants • Number analyzed indicates number of participants evaluated for this analysis.	6.8 milliunits per milliliter (mU/mL) STANDARD_DEVIATION 6.86 • n=20 Participants • Number analyzed indicates number of participants evaluated for this analysis.	6.6 milliunits per milliliter (mU/mL) STANDARD_DEVIATION 4.76 • n=49 Participants • Number analyzed indicates number of participants evaluated for this analysis.
Prolactin Level	175.4 mU/mL STANDARD_DEVIATION 73.51 • n=29 Participants • Number analyzed indicates number of participants evaluated for this analysis.	164.5 mU/mL STANDARD_DEVIATION 46.22 • n=20 Participants • Number analyzed indicates number of participants evaluated for this analysis.	170.9 mU/mL STANDARD_DEVIATION 63.46 • n=49 Participants • Number analyzed indicates number of participants evaluated for this analysis.
Testosterone Level	14.2 nanomoles per liter (nmol/L) STANDARD_DEVIATION 5.83 • n=29 Participants • Number analyzed indicates number of participants evaluated for this analysis.	11.3 nanomoles per liter (nmol/L) STANDARD_DEVIATION 5.54 • n=20 Participants • Number analyzed indicates number of participants evaluated for this analysis.	13.0 nanomoles per liter (nmol/L) STANDARD_DEVIATION 5.84 • n=49 Participants • Number analyzed indicates number of participants evaluated for this analysis.
Inhibin B Level	103.4 picograms per milliliter (pg/mL) STANDARD_DEVIATION 55.82 • n=27 Participants • Number analyzed indicates number of participants evaluated for this analysis.	149.1 picograms per milliliter (pg/mL) STANDARD_DEVIATION 98.45 • n=19 Participants • Number analyzed indicates number of participants evaluated for this analysis.	122.3 picograms per milliliter (pg/mL) STANDARD_DEVIATION 78.70 • n=46 Participants • Number analyzed indicates number of participants evaluated for this analysis.

PRIMARY outcome

Timeframe: Baseline, EOT (Week 28)

Population: Safety population. Overall number of participants analyzed=participants evaluable for this outcome measure.

Outcome measures

Outcome measures
Measure	Cohort A: Partcipants Who Received Valganciclovir n=24 Participants 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.	Cohort B: Untreated Participants n=14 Participants Participants with D-/R- CMV serology, who did not receive prophylaxis, were observed for spermatogenesis up to 52 weeks post-transplant.
Change in Sperm Density From Baseline to the End of Treatment (EOT)	-9.770 mil/mL Standard Error 9.0518	30.396 mil/mL Standard Error 11.3044

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Cohort A: Partcipants Who Received Valganciclovir n=22 Participants 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.	Cohort B: Untreated Participants n=14 Participants Participants with D-/R- CMV serology, who did not receive prophylaxis, were observed for spermatogenesis up to 52 weeks post-transplant.
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 1.7720	-5.354 percent score Standard Error 2.0680
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	-3.465 percent score Standard Error 2.5475

SECONDARY outcome

Timeframe: EOT (Week 28), end of FU (Week 52)

Population: Safety population. Overall number of participants analyzed=participants evaluable for this outcome measure.

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.

Outcome measures

Outcome measures
Measure	Cohort A: Partcipants Who Received Valganciclovir n=16 Participants 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.	Cohort B: Untreated Participants n=9 Participants Participants with D-/R- CMV serology, who did not receive prophylaxis, were observed for spermatogenesis up to 52 weeks post-transplant.
Change in TUNEL Score From EOT to End of FU	4.447 percent score Standard Error 2.0671	1.578 percent score Standard Error 2.5315

SECONDARY outcome

Timeframe: 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).

Outcome measures

Outcome measures
Measure	Cohort A: Partcipants Who Received Valganciclovir n=25 Participants 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.	Cohort B: Untreated Participants n=14 Participants Participants with D-/R- CMV serology, who did not receive prophylaxis, were observed for spermatogenesis up to 52 weeks post-transplant.
Change in Seminal Volume From Baseline to EOT and End of FU Change at EOT	-0.193 mL Standard Error 0.2324	-0.347 mL Standard Error 0.2967
Change in Seminal Volume From Baseline to EOT and End of FU Change at end of FU	-0.289 mL Standard Error 0.2066	-0.161 mL Standard Error 0.2685

SECONDARY outcome

Timeframe: EOT (Week 28), end of FU (Week 52)

Population: Safety population. Overall number of participants analyzed=participants evaluable for this outcome measure.

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).

Outcome measures

Outcome measures
Measure	Cohort A: Partcipants Who Received Valganciclovir n=20 Participants 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.	Cohort B: Untreated Participants n=9 Participants Participants with D-/R- CMV serology, who did not receive prophylaxis, were observed for spermatogenesis up to 52 weeks post-transplant.
Change in Seminal Volume From EOT to End FU	-0.103 mL Standard Error 0.2187	0.024 mL Standard Error 0.3067

SECONDARY outcome

Timeframe: EOT (Week 28), end of FU (Week 52)

Population: Safety population. Overall number of participants analyzed=participants evaluable for this outcome measure.

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).

Outcome measures

Outcome measures
Measure	Cohort A: Partcipants Who Received Valganciclovir n=19 Participants 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.	Cohort B: Untreated Participants n=9 Participants Participants with D-/R- CMV serology, who did not receive prophylaxis, were observed for spermatogenesis up to 52 weeks post-transplant.
Change in Sperm Density From EOT to End of FU	57.149 mil/mL Standard Error 17.7736	5.882 mil/mL Standard Error 27.4837

SECONDARY outcome

Timeframe: Baseline, end of FU (Week 52)

Population: Safety population. Overall number of participants analyzed=participants evaluable for this outcome measure.

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).

Outcome measures

Outcome measures
Measure	Cohort A: Partcipants Who Received Valganciclovir n=20 Participants 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.	Cohort B: Untreated Participants n=10 Participants Participants with D-/R- CMV serology, who did not receive prophylaxis, were observed for spermatogenesis up to 52 weeks post-transplant.
Change in Sperm Density From Baseline to End of FU	39.671 mil/mL Standard Error 11.6679	49.866 mil/mL Standard Error 15.8282

SECONDARY outcome

Timeframe: 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).

Outcome measures

Outcome measures
Measure	Cohort A: Partcipants Who Received Valganciclovir n=24 Participants 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.	Cohort B: Untreated Participants n=14 Participants Participants with D-/R- CMV serology, who did not receive prophylaxis, were observed for spermatogenesis up to 52 weeks post-transplant.
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	25.667 percent motility Standard Error 6.9723
Change in Total Motility of Sperm From Baseline to EOT and End of FU Change at FU	24.736 percent motility Standard Error 4.7920	34.538 percent motility Standard Error 6.6024

SECONDARY outcome

Timeframe: EOT (Week 28), end of FU (Week 52)

Population: Safety population. Overall number of participants analyzed=participants evaluable for this outcome measure.

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).

Outcome measures

Outcome measures
Measure	Cohort A: Partcipants Who Received Valganciclovir n=19 Participants 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.	Cohort B: Untreated Participants n=9 Participants Participants with D-/R- CMV serology, who did not receive prophylaxis, were observed for spermatogenesis up to 52 weeks post-transplant.
Change in Total Motility of Sperm From EOT to End of FU	8.953 percent motility Standard Error 6.3968	20.635 percent motility Standard Error 9.0663

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Cohort A: Partcipants Who Received Valganciclovir n=21 Participants 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.	Cohort B: Untreated Participants n=12 Participants Participants with D-/R- CMV serology, who did not receive prophylaxis, were observed for spermatogenesis up to 52 weeks post-transplant.
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	6.982 percentage of normal sperm cells Standard Error 4.2060
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	9.461 percentage of normal sperm cells Standard Error 5.2737

SECONDARY outcome

Timeframe: EOT (Week 28), end of FU (Week 52)

Population: Safety population. Overall number of participants analyzed=participants evaluable for this outcome measure.

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.

Outcome measures

Outcome measures
Measure	Cohort A: Partcipants Who Received Valganciclovir n=17 Participants 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.	Cohort B: Untreated Participants n=7 Participants Participants with D-/R- CMV serology, who did not receive prophylaxis, were observed for spermatogenesis up to 52 weeks post-transplant.
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 4.3420	2.236 percentage of normal sperm cells Standard Error 5.8507

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Cohort A: Partcipants Who Received Valganciclovir n=26 Participants 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.	Cohort B: Untreated Participants n=14 Participants Participants with D-/R- CMV serology, who did not receive prophylaxis, were observed for spermatogenesis up to 52 weeks post-transplant.
Change in Total Testosterone Level From Baseline to EOT and End of FU Change at EOT	0.762 nmol/L Standard Error 1.0203	2.623 nmol/L Standard Error 1.3586
Change in Total Testosterone Level From Baseline to EOT and End of FU Change at end of FU	0.395 nmol/L Standard Error 1.0260	1.509 nmol/L Standard Error 1.3074

SECONDARY outcome

Timeframe: EOT (Week 28), end of FU (Week 52)

Population: Safety population. Overall number of participants analyzed=participants evaluable for this outcome measure.

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.

Outcome measures

Outcome measures
Measure	Cohort A: Partcipants Who Received Valganciclovir n=19 Participants 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.	Cohort B: Untreated Participants n=11 Participants Participants with D-/R- CMV serology, who did not receive prophylaxis, were observed for spermatogenesis up to 52 weeks post-transplant.
Change in Total Testosterone Level From EOT to End of FU	-0.936 nmol/L Standard Error 0.9950	-0.984 nmol/L Standard Error 1.2012

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Cohort A: Partcipants Who Received Valganciclovir n=26 Participants 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.	Cohort B: Untreated Participants n=13 Participants Participants with D-/R- CMV serology, who did not receive prophylaxis, were observed for spermatogenesis up to 52 weeks post-transplant.
Change in LH Level From Baseline to EOT and End of FU Change at EOT	-0.281 mU/mL Standard Error 0.3743	-0.357 mU/mL Standard Error 0.5190
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	-0.642 mU/mL Standard Error 0.3635

SECONDARY outcome

Timeframe: EOT (Week 28), end of FU (Week 52)

Population: Safety population. Overall number of participants analyzed=participants evaluable for this outcome measure.

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.

Outcome measures

Outcome measures
Measure	Cohort A: Partcipants Who Received Valganciclovir n=20 Participants 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.	Cohort B: Untreated Participants n=11 Participants Participants with D-/R- CMV serology, who did not receive prophylaxis, were observed for spermatogenesis up to 52 weeks post-transplant.
Change in LH Level From EOT to End of FU	-1.482 mU/mL Standard Error 0.2607	-0.417 mU/mL Standard Error 0.3207

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Cohort A: Partcipants Who Received Valganciclovir n=26 Participants 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.	Cohort B: Untreated Participants n=13 Participants Participants with D-/R- CMV serology, who did not receive prophylaxis, were observed for spermatogenesis up to 52 weeks post-transplant.
Change in FSH Level From Baseline to EOT and End of FU Change at EOT	1.521 U/L Standard Error 1.0033	-1.020 U/L Standard Error 1.4072
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	-1.922 U/L Standard Error 0.5369

SECONDARY outcome

Timeframe: EOT (Week 28), end of FU (Week 52)

Population: Safety population. Overall number of participants analyzed=participants evaluable for this outcome measure.

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.

Outcome measures

Outcome measures
Measure	Cohort A: Partcipants Who Received Valganciclovir n=20 Participants 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.	Cohort B: Untreated Participants n=11 Participants Participants with D-/R- CMV serology, who did not receive prophylaxis, were observed for spermatogenesis up to 52 weeks post-transplant.
Change in FSH Level From EOT to End of FU	-3.462 U/L Standard Error 0.5036	-1.988 U/L Standard Error 0.6141

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Cohort A: Partcipants Who Received Valganciclovir n=25 Participants 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.	Cohort B: Untreated Participants n=13 Participants Participants with D-/R- CMV serology, who did not receive prophylaxis, were observed for spermatogenesis up to 52 weeks post-transplant.
Change in Prolactin Level From Baseline to EOT and End of FU Change at EOT	15.590 mU/mL Standard Error 14.4761	15.693 mU/mL Standard Error 19.2663
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	-5.443 mU/mL Standard Error 16.7203

SECONDARY outcome

Timeframe: EOT (Week 28), end of FU (Week 52)

Population: Safety population. Overall number of participants analyzed=participants evaluable for this outcome measure.

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.

Outcome measures

Outcome measures
Measure	Cohort A: Partcipants Who Received Valganciclovir n=19 Participants 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.	Cohort B: Untreated Participants n=11 Participants Participants with D-/R- CMV serology, who did not receive prophylaxis, were observed for spermatogenesis up to 52 weeks post-transplant.
Change in Prolactin Level From EOT to End of FU	-7.429 mU/mL Standard Error 10.9988	-16.169 mU/mL Standard Error 13.5322

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Cohort A: Partcipants Who Received Valganciclovir n=22 Participants 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.	Cohort B: Untreated Participants n=12 Participants Participants with D-/R- CMV serology, who did not receive prophylaxis, were observed for spermatogenesis up to 52 weeks post-transplant.
Change in Inhibin B Level From Baseline to EOT and End of FU Change at EOT	5.075 pg/mL Standard Error 7.3778	-3.067 pg/mL Standard Error 9.5924
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	10.734 pg/mL Standard Error 13.9963

SECONDARY outcome

Timeframe: EOT (Week 28), end of FU (Week 52)

Population: Safety population. Overall number of participants analyzed=participants evaluable for this outcome measure.

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.

Outcome measures

Outcome measures
Measure	Cohort A: Partcipants Who Received Valganciclovir n=18 Participants 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.	Cohort B: Untreated Participants n=9 Participants Participants with D-/R- CMV serology, who did not receive prophylaxis, were observed for spermatogenesis up to 52 weeks post-transplant.
Change in Inhibin B Level From EOT to End of FU	40.329 pg/mL Standard Error 13.8221	14.448 pg/mL Standard Error 17.8932

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Cohort A: Partcipants Who Received Valganciclovir n=24 Participants 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.	Cohort B: Untreated Participants n=14 Participants Participants with D-/R- CMV serology, who did not receive prophylaxis, were observed for spermatogenesis up to 52 weeks post-transplant.
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	35.7 percentage of participants
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	20.0 percentage of participants
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	7.1 percentage of 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	0.0 percentage of participants

SECONDARY outcome

Timeframe: EOT (Week 28), end of FU (Week 52)

Population: Safety population. Overall number of participants analyzed=participants evaluable for this outcome measure.

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.

Outcome measures

Outcome measures
Measure	Cohort A: Partcipants Who Received Valganciclovir n=19 Participants 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.	Cohort B: Untreated Participants n=9 Participants Participants with D-/R- CMV serology, who did not receive prophylaxis, were observed for spermatogenesis up to 52 weeks post-transplant.
Percentage of Participants With Abnormal Sperm Density (<20 Mil/mL) From EOT to End of FU Abnormal to abnormal	26.3 percentage of participants	22.2 percentage of 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	0.0 percentage of participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Cohort A: Partcipants Who Received Valganciclovir n=22 Participants 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.	Cohort B: Untreated Participants n=14 Participants Participants with D-/R- CMV serology, who did not receive prophylaxis, were observed for spermatogenesis up to 52 weeks post-transplant.
Percentage of Participants With Improved TUNEL Score From Baseline to EOT and End of FU EOT	72.7 percentage of participants	71.4 percentage of participants
Percentage of Participants With Improved TUNEL Score From Baseline to EOT and End of FU FU	66.7 percentage of participants	60.0 percentage of participants

SECONDARY outcome

Timeframe: EOT (Week 28), end of FU (Week 52)

Population: Safety population. Overall number of participants analyzed=participants evaluable for this outcome measure.

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.

Outcome measures

Outcome measures
Measure	Cohort A: Partcipants Who Received Valganciclovir n=16 Participants 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.	Cohort B: Untreated Participants n=9 Participants Participants with D-/R- CMV serology, who did not receive prophylaxis, were observed for spermatogenesis up to 52 weeks post-transplant.
Percentage of Participants With Improved TUNEL Score From EOT to End of FU	43.8 percentage of participants	55.6 percentage of participants

SECONDARY outcome

Timeframe: Baseline, EOT (Week 28), end of FU (Week 52)

Participants who had higher sperm density compared with the previous visit were considered as improved.

Outcome measures

Outcome measures
Measure	Cohort A: Partcipants Who Received Valganciclovir n=24 Participants 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.	Cohort B: Untreated Participants n=14 Participants Participants with D-/R- CMV serology, who did not receive prophylaxis, were observed for spermatogenesis up to 52 weeks post-transplant.
Percentage of Participants With Improved Sperm Density From Baseline to EOT and End of FU EOT	33.3 percentage of participants	64.3 percentage of participants
Percentage of Participants With Improved Sperm Density From Baseline to EOT and End of FU FU	90.0 percentage of participants	80.0 percentage of participants

SECONDARY outcome

Timeframe: EOT (Week 28), end of FU (Week 52)

Population: Safety population. Overall number of participants analyzed=participants evaluable for this outcome measure.

Participants who had higher sperm density compared with the previous visit were considered as improved.

Outcome measures

Outcome measures
Measure	Cohort A: Partcipants Who Received Valganciclovir n=19 Participants 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.	Cohort B: Untreated Participants n=9 Participants Participants with D-/R- CMV serology, who did not receive prophylaxis, were observed for spermatogenesis up to 52 weeks post-transplant.
Percentage of Participants With Improved Sperm Density From EOT to End of FU	78.9 percentage of participants	88.9 percentage of participants

Adverse Events

Cohort A: Partcipants Who Received Valganciclovir

Serious events: 10 serious events

Other events: 24 other events

Deaths: 0 deaths

Cohort B: Untreated Participants

Serious events: 12 serious events

Other events: 19 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Medical Communications

Hoffmann-La Roche

Phone: 800-821-8590

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Publication restrictions are in place

Restriction type: OTHER

Measure	Cohort A: Partcipants Who Received Valganciclovir n=31 participants at risk 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.	Cohort B: Untreated Participants n=21 participants at risk Participants with D-/R- CMV serology, who did not receive prophylaxis, were observed for spermatogenesis up to 52 weeks post-transplant.
Injury, poisoning and procedural complications Perinephric collection	0.00% 0/31 • Baseline up to end of study (Week 52) Participants who received at least one dose of valganciclovir in Cohort A and all transplanted participants of Cohort B were included for adverse events analysis.	4.8% 1/21 • Baseline up to end of study (Week 52) Participants who received at least one dose of valganciclovir in Cohort A and all transplanted participants of Cohort B were included for adverse events analysis.
Pregnancy, puerperium and perinatal conditions Fetal death	0.00% 0/31 • Baseline up to end of study (Week 52) Participants who received at least one dose of valganciclovir in Cohort A and all transplanted participants of Cohort B were included for adverse events analysis.	4.8% 1/21 • Baseline up to end of study (Week 52) Participants who received at least one dose of valganciclovir in Cohort A and all transplanted participants of Cohort B were included for adverse events analysis.
Skin and subcutaneous tissue disorders Diabetic foot	3.2% 1/31 • Baseline up to end of study (Week 52) Participants who received at least one dose of valganciclovir in Cohort A and all transplanted participants of Cohort B were included for adverse events analysis.	0.00% 0/21 • Baseline up to end of study (Week 52) Participants who received at least one dose of valganciclovir in Cohort A and all transplanted participants of Cohort B were included for adverse events analysis.
Social circumstances Treatment noncompliance	3.2% 1/31 • Baseline up to end of study (Week 52) Participants who received at least one dose of valganciclovir in Cohort A and all transplanted participants of Cohort B were included for adverse events analysis.	0.00% 0/21 • Baseline up to end of study (Week 52) Participants who received at least one dose of valganciclovir in Cohort A and all transplanted participants of Cohort B were included for adverse events analysis.
Vascular disorders Hypertension	0.00% 0/31 • Baseline up to end of study (Week 52) Participants who received at least one dose of valganciclovir in Cohort A and all transplanted participants of Cohort B were included for adverse events analysis.	4.8% 1/21 • Baseline up to end of study (Week 52) Participants who received at least one dose of valganciclovir in Cohort A and all transplanted participants of Cohort B were included for adverse events analysis.
Investigations Blood creatinine increased	0.00% 0/31 • Baseline up to end of study (Week 52) Participants who received at least one dose of valganciclovir in Cohort A and all transplanted participants of Cohort B were included for adverse events analysis.	14.3% 3/21 • Baseline up to end of study (Week 52) Participants who received at least one dose of valganciclovir in Cohort A and all transplanted participants of Cohort B were included for adverse events analysis.
General disorders Death	0.00% 0/31 • Baseline up to end of study (Week 52) Participants who received at least one dose of valganciclovir in Cohort A and all transplanted participants of Cohort B were included for adverse events analysis.	4.8% 1/21 • Baseline up to end of study (Week 52) Participants who received at least one dose of valganciclovir in Cohort A and all transplanted participants of Cohort B were included for adverse events analysis.
General disorders Pyrexia	3.2% 1/31 • Baseline up to end of study (Week 52) Participants who received at least one dose of valganciclovir in Cohort A and all transplanted participants of Cohort B were included for adverse events analysis.	0.00% 0/21 • Baseline up to end of study (Week 52) Participants who received at least one dose of valganciclovir in Cohort A and all transplanted participants of Cohort B were included for adverse events analysis.
Injury, poisoning and procedural complications Foreign body	0.00% 0/31 • Baseline up to end of study (Week 52) Participants who received at least one dose of valganciclovir in Cohort A and all transplanted participants of Cohort B were included for adverse events analysis.	4.8% 1/21 • Baseline up to end of study (Week 52) Participants who received at least one dose of valganciclovir in Cohort A and all transplanted participants of Cohort B were included for adverse events analysis.
Immune system disorders Transplant rejection	9.7% 3/31 • Baseline up to end of study (Week 52) Participants who received at least one dose of valganciclovir in Cohort A and all transplanted participants of Cohort B were included for adverse events analysis.	4.8% 1/21 • Baseline up to end of study (Week 52) Participants who received at least one dose of valganciclovir in Cohort A and all transplanted participants of Cohort B were included for adverse events analysis.
Immune system disorders Kidney transplant rejection	3.2% 1/31 • Baseline up to end of study (Week 52) Participants who received at least one dose of valganciclovir in Cohort A and all transplanted participants of Cohort B were included for adverse events analysis.	4.8% 1/21 • Baseline up to end of study (Week 52) Participants who received at least one dose of valganciclovir in Cohort A and all transplanted participants of Cohort B were included for adverse events analysis.
Infections and infestations Urinary tract infection	3.2% 1/31 • Baseline up to end of study (Week 52) Participants who received at least one dose of valganciclovir in Cohort A and all transplanted participants of Cohort B were included for adverse events analysis.	4.8% 1/21 • Baseline up to end of study (Week 52) Participants who received at least one dose of valganciclovir in Cohort A and all transplanted participants of Cohort B were included for adverse events analysis.
Infections and infestations Atypical pneumonia	0.00% 0/31 • Baseline up to end of study (Week 52) Participants who received at least one dose of valganciclovir in Cohort A and all transplanted participants of Cohort B were included for adverse events analysis.	4.8% 1/21 • Baseline up to end of study (Week 52) Participants who received at least one dose of valganciclovir in Cohort A and all transplanted participants of Cohort B were included for adverse events analysis.
Infections and infestations Gastroenteritis	0.00% 0/31 • Baseline up to end of study (Week 52) Participants who received at least one dose of valganciclovir in Cohort A and all transplanted participants of Cohort B were included for adverse events analysis.	4.8% 1/21 • Baseline up to end of study (Week 52) Participants who received at least one dose of valganciclovir in Cohort A and all transplanted participants of Cohort B were included for adverse events analysis.
Infections and infestations Pyelonephritis	0.00% 0/31 • Baseline up to end of study (Week 52) Participants who received at least one dose of valganciclovir in Cohort A and all transplanted participants of Cohort B were included for adverse events analysis.	4.8% 1/21 • Baseline up to end of study (Week 52) Participants who received at least one dose of valganciclovir in Cohort A and all transplanted participants of Cohort B were included for adverse events analysis.
Infections and infestations Sinusitis	3.2% 1/31 • Baseline up to end of study (Week 52) Participants who received at least one dose of valganciclovir in Cohort A and all transplanted participants of Cohort B were included for adverse events analysis.	0.00% 0/21 • Baseline up to end of study (Week 52) Participants who received at least one dose of valganciclovir in Cohort A and all transplanted participants of Cohort B were included for adverse events analysis.
Renal and urinary disorders Acute kidney injury	9.7% 3/31 • Baseline up to end of study (Week 52) Participants who received at least one dose of valganciclovir in Cohort A and all transplanted participants of Cohort B were included for adverse events analysis.	4.8% 1/21 • Baseline up to end of study (Week 52) Participants who received at least one dose of valganciclovir in Cohort A and all transplanted participants of Cohort B were included for adverse events analysis.
Renal and urinary disorders Hematuria	3.2% 1/31 • Baseline up to end of study (Week 52) Participants who received at least one dose of valganciclovir in Cohort A and all transplanted participants of Cohort B were included for adverse events analysis.	0.00% 0/21 • Baseline up to end of study (Week 52) Participants who received at least one dose of valganciclovir in Cohort A and all transplanted participants of Cohort B were included for adverse events analysis.
Renal and urinary disorders Renal artery stenosis	0.00% 0/31 • Baseline up to end of study (Week 52) Participants who received at least one dose of valganciclovir in Cohort A and all transplanted participants of Cohort B were included for adverse events analysis.	4.8% 1/21 • Baseline up to end of study (Week 52) Participants who received at least one dose of valganciclovir in Cohort A and all transplanted participants of Cohort B were included for adverse events analysis.
Renal and urinary disorders Tubulointerstitial nephritis	3.2% 1/31 • Baseline up to end of study (Week 52) Participants who received at least one dose of valganciclovir in Cohort A and all transplanted participants of Cohort B were included for adverse events analysis.	0.00% 0/21 • Baseline up to end of study (Week 52) Participants who received at least one dose of valganciclovir in Cohort A and all transplanted participants of Cohort B were included for adverse events analysis.
Gastrointestinal disorders Diarrhea	3.2% 1/31 • Baseline up to end of study (Week 52) Participants who received at least one dose of valganciclovir in Cohort A and all transplanted participants of Cohort B were included for adverse events analysis.	0.00% 0/21 • Baseline up to end of study (Week 52) Participants who received at least one dose of valganciclovir in Cohort A and all transplanted participants of Cohort B were included for adverse events analysis.
Gastrointestinal disorders Nausea	3.2% 1/31 • Baseline up to end of study (Week 52) Participants who received at least one dose of valganciclovir in Cohort A and all transplanted participants of Cohort B were included for adverse events analysis.	0.00% 0/21 • Baseline up to end of study (Week 52) Participants who received at least one dose of valganciclovir in Cohort A and all transplanted participants of Cohort B were included for adverse events analysis.
Gastrointestinal disorders Rectal hemorrhage	3.2% 1/31 • Baseline up to end of study (Week 52) Participants who received at least one dose of valganciclovir in Cohort A and all transplanted participants of Cohort B were included for adverse events analysis.	0.00% 0/21 • Baseline up to end of study (Week 52) Participants who received at least one dose of valganciclovir in Cohort A and all transplanted participants of Cohort B were included for adverse events analysis.
Gastrointestinal disorders Retroperitoneal hematoma	0.00% 0/31 • Baseline up to end of study (Week 52) Participants who received at least one dose of valganciclovir in Cohort A and all transplanted participants of Cohort B were included for adverse events analysis.	4.8% 1/21 • Baseline up to end of study (Week 52) Participants who received at least one dose of valganciclovir in Cohort A and all transplanted participants of Cohort B were included for adverse events analysis.