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

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

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.

Study Overview

• Status: Completed
• Conditions: Kidney Transplantation, Cytomegalovirus Infections
• Intervention / Treatment: Drug: valganciclovir [Valcyte]

• Study Type: Interventional
• Enrollment (Actual): 57
• Phase: Phase 4

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Westmead, New South Wales, Australia, 2145
      • Children'S Hospital At Westmead; Department of Nephrology
  • Queensland
    • South Brisbane, Herston, Queensland, Australia, 4029
      • Mater Childrens Hospital
  • Victoria
    • Parkville, Victoria, Australia, 3052
      • Royal Children'S Hospital; Department of Nephrology
• Brazil
  • SP
    • Sao Paulo, SP, Brazil, 04038-002
      • Universidade Federal de São Paulo - UNIFESP
• France
  • Nantes, France, 44093
    • CHU de Nantes - Service de pédiatrie
  • Paris, France, 75019
    • Hôpital Robert Debré; Nephrologie pediatrique
  • Paris, France, 75743
    • Hop Necker Enfants Malades;Nephrologie Pediatrique
• Germany
  • Hamburg, Germany, 20246
    • Universitätsklinikum für Kinder und Jugendmedizin Hamburg
  • Hannover, Germany, 30625
    • KfH Nierenzentrum für Kinder und Jugendliche an der MHH Hannover
  • Heidelberg, Germany, 69120
    • Klinik Kinderheikunde I des Zentrums für Kinder- und Jugendmedizin, Universität Heidelberg
  • Köln, Germany, 50937
    • Klinik und Poliklinik für Kinder- und Jugendmedizin- Köln, Uniklinik Köln
• Mexico
  • Aguascalientes, Mexico, 20230
    • Centenario Hospital Miguel Hidalgo
  • Cuernavaca, Mexico, 62428
    • Instituto Mexicano de Transplantes
  • Mexico, Mexico, 06720
    • Hospital Infantil de Mexico Federico Gomez
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebron
  • Madrid, Spain, 28046
    • Hospital Universitario La Paz: Nefrologia Pediatrica
  • Sevilla, Spain, 41013
    • Hospital Universitario Virgen del Rocio; Servicio de Nefrologia Pediatrica
• Sweden
  • Göteborg, Sweden, 41345
    • Sahlgrenska Sjukhuset; Transplantationskirurgiska Kliniken
• United Kingdom
  • Birmingham, United Kingdom, B4 6NH
    • Birmingham Children's Hospital
  • Bristol, United Kingdom, BS2 8BJ
    • Bristol Royal Hospital for Children
  • Glasgow, United Kingdom, G3 8SJ
    • Royal Hospital For Sick Children; Dept. of Child Health
• United States
  • Florida
    • Gainesville, Florida, United States
      • University of Florida Pediatric Nephrology
  • Louisiana
    • Los angeles, Louisiana, United States, 90095-1752
      • UCLA Center For Health Sciences; Division of Pediatric Nephrology
  • New York
    • New York, New York, United States, 10029-6574
      • Mount Sinai Medical Center
  • Utah
    • Salt Lake City, Utah, United States, 84108
      • Uni of Utah Health Science Center; Pediatric Nephrology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 months to 16 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Valganciclovir; 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]; Oral, daily for up to 200 days.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start (Actual): July 31, 2011
• Primary Completion (Actual): May 31, 2013
• Study Completion (Actual): May 31, 2013

Study Registration Dates

• First Submitted: June 17, 2011
• First Submitted That Met QC Criteria: June 17, 2011
• First Posted (Estimate): June 20, 2011

Study Record Updates

• Last Update Posted (Actual): July 11, 2017
• Last Update Submitted That Met QC Criteria: June 15, 2017
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Virus Diseases; Infections; DNA Virus Infections; Herpesviridae Infections; Cytomegalovirus Infections; Anti-Infective Agents; Antiviral Agents; Valganciclovir
• Other Study ID Numbers: NV25409; 2010-022514-47 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No