Clinical trial NCT00001125: Use of a Varicella-Zoster Virus (VZV) Vaccine to Prevent Shingles in HIV-Infected Children Who Have Already Had Chickenpox
Official title: Use of a Live-Attenuated Varicella-Zoster Virus (VZV) Vaccine to Boost Immunity to VZV in HIV-Infected Children Previously Infected With Varicella
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: HIV Infections
Chickenpox
Keywords: Antibodies, Viral
Chickenpox
Chickenpox Vaccine
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
Collaborators: name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
First posted: 2001-08-31
Enrollment: 60
Sex: ALL
Minimum age (years): 2
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Primary purpose: PREVENTION

Brief summary: The purpose of this study is to see if the varicella-zoster virus (VZV) vaccine will be safe and if it can help prevent shingles in HIV-infected children who have already had chickenpox.

VZV is the virus that causes chickenpox. If this virus is reactivated in the body, it can also cause shingles. Shingles is common in children with HIV who have had chickenpox, although it is usually not life-threatening. The VZV vaccine used in this study may be able to prevent HIV-positive children who have had chickenpox from developing shingles.

Detailed description: Varicella (chickenpox) results from primary infection with VZV. Varicella, a common and usually benign illness in normal children, is more severe in HIV-infected children and may result in other conditions such as HZ (shingles). HZ is due to reactivation of latent VZV acquired during varicella and is common in HIV-infected children who have had natural varicella. While HZ is not likely to be life-threatening in these children, it does cause considerable morbidity and interferes with quality of life. Use of a live-attenuated VZV vaccine may be able to boost immunity in these children.

Two immunologic cohorts are enrolled. Cohort A includes children with a CD4 cell percentage greater than or equal to 20 percent that has been documented as stable for at least the 6 months prior to the time varicella developed (confirmed by a minimum of 2 tests) and a CD4 cell percentage greater than \[AS PER AMENDMENT 10/27/99: or equal to\] 15 percent that has been documented as stable for at least the 6 months prior to enrollment (confirmed by a minimum of 2 tests). Cohort B includes children with a CD4 cell percentage greater than or equal to 10 percent and less than 15 percent that has been documented as stable for at least the 6 months prior to the time varicella developed and stable for at least the 6 months prior to enrollment (confirmed by a minimum of 2 tests). \[AS PER AMENDMENT 4/20/01: Cohort B includes children who have a CD4 cell percentage less than 15% documented by a minimum of 1 but preferably 2 tests within 1 year of onset of varicella (i.e., within 1 year before to 1 year after varicella) and a CD4 cell percentage greater than or equal to 15% documented by a minimum of 2 tests at the time of enrollment.\] A pilot study precedes the full study. \[AS PER AMENDMENT 10/27/99: The pilot study for Cohort A precedes the full study for Cohort A and the pilot study for Cohort B. The pilot study for Cohort B precedes the full study for Cohort B.\] The pilot study includes 10 children from each cohort who receive live-attenuated VZV at Weeks 0 and 8. If 3 pilot-study patients in a cohort meet a toxicity endpoint related to the vaccine, the dose regimen has failed the safety criteria for that cohort. \[AS PER AMENDMENT 10/27/99: If 3 children in the pilot study for Cohort A meet a toxicity endpoint deemed to be related to the vaccine, the dose regimen has failed safety criteria for both cohorts. If 3 children in the pilot phase of Cohort B meet a toxicity endpoint deemed related to the vaccine, the dose regimen has failed the safety criteria for Cohort B.\] If, at 12 weeks after immunization, at least 5 pilot-study patients in a cohort respond and the safety profile is deemed adequate, the pilot study extends into a full study with the immunization of an additional 20 patients from that cohort. \[AS PER AMENDMENT 10/27/99: If, at Week 12, at least 5 pilot-study patients in Cohort A meet immunologic criteria and the safety profile is deemed adequate, then the full study for Cohort A and the pilot study for Cohort B opens. If the same immunologic and safety criteria are met for the pilot study for Cohort B, then the full study for Cohort B opens.\] If either cohort shows an inadequate immunologic response or safety profile, the study team reviews the results to determine if another regimen should be considered. In the full study, patients receive 2 immunizations, at Weeks 0 and 8. Varicella antibody titers and in vitro responder cell frequency (RCF) assays are measured at Weeks 0, 4, 8, 12, 24, 52, 78, and 104. Symptoms, HIV progression, and VZV presence are monitored throughout the study.

Eligibility criteria: Inclusion Criteria

Children may be eligible for this study if they:

* Are 2 to 18 years old (need consent of parent or guardian if under 18).
* Are HIV-positive.
* Are VZV-positive.
* Have a CD4 cell percentage of at least 15 percent at the time of enrollment. (This criterion reflects a change from the original CD4 cell percentage.)
* Have been receiving stable anti-HIV therapy for at least 3 months, with no plans to change these medications.
* Had chickenpox at least 6 months prior to study entry.
* Were at least 1 year old when they had chickenpox.
* Agree to use a barrier method of birth control (such as a condom) during the study.

Exclusion Criteria

Children will not be eligible for this study if they:

* Have an active infection within 72 hours of study entry.
* Have a fever over 101 F within 72 hours of study entry.
* Were exposed to chickenpox or shingles within 4 weeks prior to study entry.
* Have ever had shingles.
* Live with someone who has HIV, or who has a weak immune system, and has never had chickenpox.
* Have taken certain medications that affect the immune system, such as steroids, within 30 days of study entry.
* Have taken or are planning to take VZIG or IVIG within 1 year prior to or 2 months after a study vaccination.
* Are allergic to the vaccine, or to neomycin.
* Have received or expect to receive another vaccine within 30 days prior to or 30 days after a study vaccination.
* Have ever received a chickenpox vaccine.
* Are taking aspirin or expect to use aspirin 6 weeks after a study vaccination.
* Have taken or plan to take any anti-herpes drugs within 1 week before or 3 weeks after a study vaccination.
* Have received or plan to receive a blood transfusion within 1 year before or 2 months after a study vaccination.
* Have certain medical problems that would interfere with the study.
* Are pregnant or breast-feeding.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Long Beach
country: United States
facility: Long Beach Memorial Med. Ctr., Miller Children's Hosp.
state: California
city: Los Angeles
country: United States
facility: Usc La Nichd Crs
state: California
city: Los Angeles
country: United States
facility: UCLA-Los Angeles/Brazil AIDS Consortium (LABAC) CRS
state: California
city: Torrance
country: United States
facility: Harbor - UCLA Med. Ctr. - Dept. of Peds., Div. of Infectious Diseases
state: California
city: Fort Lauderdale
country: United States
facility: South Florida CDTC Ft Lauderdale NICHD CRS
state: Florida
city: Jacksonville
country: United States
facility: Univ. of Florida Jacksonville NICHD CRS
state: Florida
city: Miami
country: United States
facility: Univ. of Miami Ped. Perinatal HIV/AIDS CRS
state: Florida
city: Boston
country: United States
facility: HMS - Children's Hosp. Boston, Div. of Infectious Diseases
state: Massachusetts
city: Boston
country: United States
facility: BMC, Div. of Ped Infectious Diseases
state: Massachusetts
city: Springfield
country: United States
facility: Baystate Health, Baystate Med. Ctr.
state: Massachusetts
city: Camden
country: United States
facility: Cooper Univ. Hosp.
state: New Jersey
city: Newark
country: United States
facility: NJ Med. School CRS
state: New Jersey
city: New York
country: United States
facility: Nyu Ny Nichd Crs
state: New York
city: New York
country: United States
facility: Cornell Univ., Div. of Ped. Infectious Diseases & Immunology
state: New York
city: New York
country: United States
facility: Columbia IMPAACT CRS
state: New York
city: New York
country: United States
facility: Harlem Hosp. Ctr. NY NICHD CRS
state: New York
city: Rochester
country: United States
facility: Strong Memorial Hospital Rochester NY NICHD CRS
state: New York
city: Syracuse
country: United States
facility: SUNY Upstate Med. Univ., Dept. of Peds.
state: New York
city: Philadelphia
country: United States
facility: The Children's Hosp. of Philadelphia IMPAACT CRS
state: Pennsylvania
city: Philadelphia
country: United States
facility: St. Christopher's Hosp. for Children
state: Pennsylvania
city: Memphis
country: United States
facility: St. Jude/UTHSC CRS
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt Univ. Med. Ctr., Div. of Ped. Infectious Diseases
state: Tennessee
Study officials:
name: Anne Gershon
role: STUDY_CHAIR
References: