A Study of Oral Valcyte (Valganciclovir) in Pediatric Kidney Transplant Recipients

Study Overview
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Brief Summary
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This open-label, single arm study will evaluate the tolerability and efficacy of Valcyte (valganciclovir) in the prevention of cytomegalovirus disease in pediatric renal transplant recipients. After transplantation, patients (aged 4 months to 16 years) will receive Valcyte orally daily for up to 200 days post-transplant and will be followed for 52 weeks post-transplantation.

Official Title
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Tolerability of up to 200 Days of Valganciclovir Oral Solution or Tablets in Pediatric Kidney Transplant Recipients

Conditions
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Kidney Transplantation, Cytomegalovirus Infections

Intervention / Treatment
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* Drug: valganciclovir [Valcyte]


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Children, 4 months to 16 years of age Patient has received a kidney transplant At risk of developing cytomegalovirus disease Adequate hematological and renal function Able to tolerate oral medication Negative pregnancy test for females of childbearing potential Exclusion Criteria: Allergic or significant adverse reaction to acyclovir, valacyclovir or ganciclovir in the past Severe uncontrolled diarrhea (more than 5 watery stools per day) Liver enzyme elevation of more than five times the upper limit of normal for aspartate aminotransferase [AST (SGOT)] or alanine aminotransferase [ALT (SGPT)] Patient requires use of any protocol prohibited concomitant medication Previous participation in this clinical study

Ages Eligible for Study
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Minimum Age: 4 Months
Maximum Age: 16 Years

Sexes Eligible for Study
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All

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: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Valganciclovir<br>Participants received a once daily oral dose (solution or tablets) of valganciclovir starting within 10 days of kidney transplant for up to 200 days post-transplant. Dose (in milligrams) was calculated using the algorithm [7 * Body Surface Area * Creatinine Clearance]. | Drug: valganciclovir [Valcyte]<br>* Oral, daily for up to 200 days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events (AE), Serious Adverse Events (SAE) or Withdrawal Due to AEs | An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not considered related to the medicinal (investigational) product. Pre-existing conditions which worsen during a study were reported as AEs. A SAE was any experience that: resulted in death, was life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect or was medically significant. | 52 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Cytomegalovirus (CMV) Infection in the First 52 Weeks Post-Transplant as Assessed by the Investigator | A polymerase chain reaction (PCR) based assay or antigenaemia assay was used for the qualitative assessment of CMV viremia (presence of CMV in the blood) by each study center as part of the clinical assessment required for diagnosis of CMV infection. | 52 weeks | 
| Number of Participants With Cytomegalovirus (CMV) Disease in the First 52 Weeks Post-Transplant as Assessed by the Investigator | A polymerase chain reaction (PCR) based assay or antigenaemia assay was used for the qualitative assessment of CMV viremia by each study center as part of the clinical assessment required for diagnosis of CMV infection. CMV disease included CMV syndrome or tissue invasive CMV. CMV syndrome required fever ≥ 38 degrees Celsius, severe malaise, leukopenia on 2 separate measurements, atypical lymphocytosis ≥ 5%, thrombocytopenia, elevation of hepatic transaminases and presence of CMV in blood. Tissue Invasive CMV required evidence of localized CMV infection in a biopsy or other appropriate symptom and relevant symptoms or signs of organ dysfunction. | 52 weeks | 
| Number of Participants With Peak Cytomegalovirus (CMV) Viral Load up to Week 52 Post-Transplant | Blood samples were sent to a central lab for the quantitative assessment of CMV viral load (amount of CMV in the blood) by an FDA-approved molecular-based assay. The number of participants in each category is reported in copies/milliliter (CP/mL). CMV DNA is detected in all categories < 150 CP/mL and above. | 52 weeks | 
| Number of Participants With Biopsy Proven Rejection | Renal biopsies were performed as medically indicated. Biopsies were assessed histologically using the updated Banff criteria 1997. | 52 Weeks | 
| Number of Participants With Graft Loss | Graft loss was defined as the institution of chronic dialysis (at least 6 consecutive weeks), transplant nephrectomy, or retransplantation. | 52 Weeks | 
| Number of Participants With Death |  | 52 Weeks | 
| Number of Participants With Known Ganciclovir Resistance (Mutations in Either UL54 or UL97 Genes) | All patients with measurable CMV had both UL54 and UL97 genes sequenced to assess for known CMV resistance to ganciclovir. | 52 Weeks |