Evaluation of the Safety of Varivax® in Pediatric Renal Transplant Recipients

Kidney Transplant Recipients Clinical Trial

Official title:

Evaluation of the Safety and Immunogenicity of Varivax® (Live-Attenuated Varicella-Zoster Virus Vaccine) in Pediatric Renal Transplant Recipients

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00005009
• Other study ID #: DAIT VZV
• Status: Terminated
• Phase: Phase 1
• First received: March 28, 2000
• Last updated: February 14, 2017
• Start date: February 1998
• Est. completion date: June 16, 2001

Study information

• Verified date: February 2017
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to find out whether Varivax is safe for use in children with kidney transplants and whether it protects children from serious infection. Varivax is a vaccine against varicella zoster virus (VZV), the virus that causes chickenpox (varicella) and shingles (zoster).

Healthy children are already receiving Varivax shots to protect them from chickenpox. Few children with kidney transplants have received Varivax because doctors have been concerned that Varivax might cause serious reactions in them. On the other hand, VZV infection can be a life-threatening disease in these children. For this reason, doctors ultimately want to learn whether Varivax might safely prevent VZV infections in children who have had kidney transplants.

Description:

Pediatric renal transplant patients face a lifetime of immunosuppressive therapy that place them at high risk for potentially life-threatening infection by primary varicella zoster virus (VZV). Treatment for acute episodes of VZV infection is possible but expensive and provides no long-term protection. Furthermore, therapy to overcome VZV infections can lead to renal graft rejection.

Varivax has proven safe, immunogenic, and effective in the normal host and has been recommended for universal administration in the general population at age 12 months. It is not currently labeled for use in immunocompromised patients. However, recent studies in pediatric leukemia and pediatric renal transplant patients suggest that attenuated live vaccine can confer protection with minimal adverse events even in the presence of immunosuppression, providing encouragement for more careful studies of VZV immunization in renal transplant patients. This study aims to quantify the safety and immunogenicity of Varivax in the population of pediatric renal transplant patients least susceptible to VZV infection, i.e., those on minimal maintenance immunosuppression and at least 1 year out from transplant.

Patient enrollment is staged to allow study physicians to closely monitor patients for signs of disseminated varicella reactions or graft rejection. Initially only 1 patient will be enrolled in the study. If the first patient reaches Week 8 without a severe adverse reaction, 3 study centers will then enroll 3 additional patients. If 8 weeks later these 3 patients have had no severe adverse reactions, the same 3 study centers will enroll 3 more patients. At the end of this period, having ascertained the safety of the vaccine in the first 7 patients, the study will be opened to the remaining centers. Patients receive 2 doses of Varivax 6 to 8 weeks apart. Each week for 6 to 8 weeks after the first vaccine dose, the patient undergoes venipuncture and clinical assessment to characterize renal graft and liver function and identify any signs of varicella infection. Additional telephone follow-up occurs on Day 4 and twice weekly thereafter. Parents or guardians monitor the patient for evidence of rash or fever and immediately report any rashes or fevers to study physicians. If, after 6 to 8 weeks, the patient demonstrates no severe reactions to the vaccine and requires no antiviral therapy, the patient receives the second vaccine dose. The patient again receives weekly on-site and telephone follow-up for 6 weeks. Other visits occur 9 weeks and 14 weeks after the second vaccine dose and 1 year after the first vaccine dose. At these visits the patient undergoes venipuncture and clinical assessment to identify potential rejection events or varicella infection and to characterize VZV antibody responses and cytokine changes in response to the vaccine.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 7
• Est. completion date: June 16, 2001
• Est. primary completion date: June 16, 2001
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years to 21 Years

Eligibility

Inclusion Criteria:

Your child may be eligible for this trial if he/she:

• Had a kidney transplant 1 year ago or more;

• Is between 2 and 21 years of age (parent or guardian's signed informed consent required if under 18);

• Is taking stable, maintenance doses of immunosuppressive drugs for his/her kidney transplant; and

• Is generally in good health.

Exclusion Criteria:

Your child will not be eligible for this trial if he/she:

• Has had any rejection episodes in the last 6 months or has other problems with their kidneys;

• Was in the hospital for a major infection in the last 30 days;

• Has a history of VZV infection, including chicken pox or shingles;

• Has ever received a VZV vaccine, including Varivax®;

• Lives with a person whose immune system does not work well;

• Is allergic to certain medications;

• Is unable to return for the prescribed follow-up check-ups;

• Has no phone or pager; or

• Has had blood or plasma transfusions or taken certain drugs in the last 6 months.

Related Conditions & MeSH terms

• Herpes Zoster
• Kidney Transplant Recipients

Intervention

Biological:
• Varivax®
Each participant will receive 2 doses of Varivax 6 to 8 weeks apart.

Locations

Country	Name	City	State
United States	University of Michigan - Vaccine and Treatment Evaluation Unit (VTEU)	Ann Arbor	Michigan
United States	University of Alabama at Birmingham - Vaccine and Treatment Evaluation Unit (VTEU)	Birmingham	Alabama
United States	Boston Children's Hospital - Vaccine and Treatment Evaluation Unit (VTEU)	Boston	Massachusetts
United States	University of Texas Health Science Center at San Antonio - Vaccine and Treatment Evaluation Unit (VTEU)	San Antonio	Texas

Sponsors (5)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)	Cooperative Clinical Trials in Pediatric Transplantation, Merck Sharp & Dohme Corp., NIAID Vaccine and Treatment Evaluation Units (VTEUs), North American Pediatric Renal Trials and Collaborative Studies (NAPRTCS)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Immediate adverse reactions		30 minutes post vaccination
Primary	Varicella related adverse reactions	Fever and local (<1 inch from inoculation site) lesions; Fever and lesions outside the 1 inch inoculation site; Lesions outside the 1 inch inoculation site; Clinical signs of pneumonitis; Clinical or chemical signs of hepatitis; Development of thrombocytopenia	1 year
Primary	Rejection events	Increase in creatinine; Renal biopsy	1 year

External Links

•   Division of Allergy, Immunology, and Transplantation (DAIT) website
•   National Institute of Allergy and Infectious Diseases (NIAID) website
•   NIAID Vaccine and Treatment Evaluation Units (VTEUs)
•   North American Pediatric Renal Trials and Collaborative Studies (NAPRTCS)