Clinical trial NCT00000879: A Study of the Effects of Giving Two Anti-HIV Vaccines to Babies of HIV-Positive Mothers
Official title: A Phase I/II Study to Evaluate the Safety and Immunogenicity of ALVAC HIV Vaccines Alone and With AIDSVAX B/B in Children Born to HIV-Infected Mothers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: HIV Infections
HIV Seronegativity
Keywords: Pregnancy
Pregnancy Complications, Infectious
AIDS Vaccines
Disease Transmission, Vertical
Avipoxvirus
HIV Preventive Vaccine
HIV Therapeutic 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: 48
Sex: ALL
Minimum age (years): 0
Maximum age (years): 3
Standard ages: CHILD
Accepts healthy volunteers: no
Primary purpose: PREVENTION

Brief summary: The purpose of this study is to see if giving the ALVAC vCP1452 anti-HIV vaccine alone or with another vaccine called AIDSVAX B/B to babies of HIV-positive mothers is safe. The study will also look at how these vaccines affect a baby's immune system. Most HIV-positive children get HIV from their mothers during pregnancy or birth. Treatment with anti-HIV drugs can reduce the baby's risk of getting HIV. Vaccines also may help prevent HIV infection. This study will look at whether the ALVAC vCP1452 vaccine and the AIDSVAX B/B vaccine can help the body fight off HIV infection. There is no chance of getting HIV infection from the vaccines. (This study has been changed. In earlier versions, ALVAC vCP205 and AIDSVAX B/E were going to be used.)

Detailed description: Transmission of HIV from an untreated infected mother to her offspring is thought to occur to some infants perinatally and others at parturition. It is possible that administration of an immunogenic vaccine can reduce the vertical transmission of HIV-1 or moderate its course in infected infants. Successful early sensitization to HIV epitopes might succeed in preventing HIV infection. Alternately, the enhancement of HIV-specific immune function might also succeed in modifying HIV replication and affecting disease progression.

Sixty infants are treated in this randomized, double-blind study; 45 infants receive recombinant Canarypox virus, ALVAC-HIV vCP205, and 15 receive placebo. Mothers serve as proxy for their infants. All infants receive a minimum of four immunizations, at Weeks 0 (within 72 hours of birth), 4, 8, and 12. Initially, 24 patients are randomized to receive one of two doses of vCP205 or a saline placebo. When a suitable subunit vaccine is available, the protocol will be amended and 36 additional infants will be randomized to receive vCP205 alone or with a subunit vaccine at Weeks 4 and 8 (or vaccine placebo with or without subunit placebo). \[AS PER AMENDMENT 11/5/97: 18 infants receive ALVAC-HIV vCP205 at one of two doses and 6 receive placebo.\] \[AS PER AMENDMENT 9/9/99: Cohort 1 received vCP205. Cohort 2 received a higher dose of vCP205. Cohort A received vCP205 placebo (saline). Cohorts 1, 2, and A were double-blinded and closed to accrual in March 1999. As of September 1999, infants are randomized to one of four new cohorts. Cohort 3 receives vCP1452 at Weeks 0, 4, 8, and 12. Cohort 4 receives vCP1452 at Weeks 0 and 4, then receives vCP1452 plus AIDSVAX B/E gp120 at Weeks 8 and 12. Cohort B receives vCP1452 placebo at Weeks 0, 4, 8, and 12. Cohort C receives vCP1452 placebo at Weeks 0 and 4, then receives vCP1452 placebo plus AIDSVAX B/E placebo at Weeks 8 and 12. All infants are followed every 2 weeks for the first 14 weeks of life, and then every 6 months until age 2. Cord blood is used to establish autologous B cell lines, and CTL assays are performed to characterize the immune response to HIV. In addition, CD4 count, viral load, and mucosal antibody responses are measured. Immunized infants who are not infected with HIV serve as controls for the immunogenicity of the vaccines in the infected infants.\] \[AS PER AMENDMENT 1/24/00: AIDSVAX B/E has been replaced with AIDSVAX B/B.\]

Eligibility criteria: Inclusion Criteria

The infant may be eligible if the mother:

* Is HIV-positive.
* Is willing to follow the study guidelines.
* Had her baby at Week 37 of pregnancy or later.

Exclusion Criteria

The infant will not be eligible if the mother:

* Has hepatitis B.
* Is breast-feeding her baby.
* Used certain medications during pregnancy.

The infant will not be eligible if he/she:

* Is more than 3 days old at study entry.
* Has a serious infection or life-threatening illness.

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: Orange
country: United States
facility: Children's Hosp. of Orange County
state: California
city: San Francisco
country: United States
facility: UCSF Pediatric AIDS CRS
state: California
city: Torrance
country: United States
facility: Harbor - UCLA Med. Ctr. - Dept. of Peds., Div. of Infectious Diseases
state: California
city: Chicago
country: United States
facility: Mt. Sinai Hosp. Med. Ctr. - Chicago, Womens & Childrens HIV Program
state: Illinois
city: Chicago
country: United States
facility: Chicago Children's CRS
state: Illinois
city: New Orleans
country: United States
facility: Tulane Univ. Health Science Ctr., Tulane Univ. Hosp. & Clinic
state: Louisiana
city: Baltimore
country: United States
facility: Univ. of Maryland Med. Ctr., Div. of Ped. Immunology & Rheumatology
state: Maryland
city: Boston
country: United States
facility: HMS - Children's Hosp. Boston, Div. of Infectious Diseases
state: Massachusetts
city: Worcester
country: United States
facility: WNE Maternal Pediatric Adolescent AIDS CRS
state: Massachusetts
city: Bronx
country: United States
facility: Jacobi Med. Ctr. Bronx NICHD CRS
state: New York
city: New York
country: United States
facility: Nyu Ny Nichd Crs
state: New York
city: New York
country: United States
facility: Columbia IMPAACT 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: Univ. of Pennsylvania Health System, Hosp. of the Univ. of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: The Children's Hosp. of Philadelphia IMPAACT CRS
state: Pennsylvania
city: Seattle
country: United States
facility: Seattle Children's Hospital CRS
state: Washington
Study officials:
name: John Lambert
role: STUDY_CHAIR
name: Daniel Johnson
role: STUDY_CHAIR
name: Stuart Starr
role: STUDY_CHAIR
References:
citation: Johnson D, McFarland E, Muresan P, Fenton T, Lambert J, McNamara J, Hawkins E, Bouquin P, Read J, Estep S, Gunurathan S, Gurwith M, PACTG 326 Protocol Team. PACTG 326: A Phase I/II Study to Evaluate the Safety and Immunogenicity of Alvac HIV Vaccines Alone and with AIDSVax B/B in Children Born to HIV-infected Mothers: Preliminary Results. 10th Conference on Retroviruses and Oppurtunistic Infections. Feb 2003. Abstract 404.
citation: Lambert JS. HIV vaccines in infants and children. Paediatr Drugs. 2005;7(5):267-76. doi: 10.2165/00148581-200507050-00001.