Clinical trial NCT00000774: A Phase I Study to Evaluate the Safety and Immunogenicity of Recombinant HIV-1 Envelope Antigen in Children Born to HIV-Infected Mothers
Official title: A Phase I Study to Evaluate the Safety and Immunogenicity of Recombinant HIV-1 Envelope Antigen in Children Born to HIV-Infected Mothers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: HIV Infections
HIV Seronegativity
Keywords: Vaccines, Synthetic
Virus Replication
HIV Envelope Protein gp120
AIDS Vaccines
HIV Preventive Vaccine
HIV Therapeutic Vaccine
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
Collaborators: name: Genentech, Inc.
name: Biocine
First posted: 2001-08-31
Enrollment: 156
Sex: ALL
Minimum age (years): 1
Maximum age (years): 3
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: PRIMARY: To determine the safety of envelope recombinant proteins rgp120/HIV-1MN (Genentech) and rgp120/HIV-1SF2 (Chiron/Biocine) in infants who are of indeterminate HIV status born to HIV-infected women. To evaluate changes in viral load in infants proven to be infected and absolute CD4 counts in all immunized infants.

SECONDARY: To evaluate the immunogenicity of these envelope recombinant proteins in infants of indeterminate HIV status born to HIV-infected women.

Only 30-50 percent of HIV-infected infants have detectable virus at birth. Successful early sensitization to HIV envelope epitopes may help prevent infection or, alternatively, may enhance HIV-specific immune function to alter HIV replication and disease progression.

Detailed description: Only 30-50 percent of HIV-infected infants have detectable virus at birth. Successful early sensitization to HIV envelope epitopes may help prevent infection or, alternatively, may enhance HIV-specific immune function to alter HIV replication and disease progression.

Newborns are randomized to one of three different doses of either rgp120/HIV-1MN or rgp120/HIV-1SF2 or their matching placebos. At each dose level, 12 patients receive vaccine and three patients receive placebo. Immunizations are performed at 0, 4, 12, and 20 weeks, and patients are followed until 2 years of age. Three of four patients treated at a given dose level must have received two immunizations without evidence of grade 3 or 4 clinical or laboratory toxicity before dose escalation occurs. Twelve additional patients are treated with the optimal dose of each vaccine at weeks 0, 2, 8, and 20 (An accelerated schedule PER AMENDMENT 3/20/96. Changed from - 0, 4, 8, and 20) accompanied by three additional placebo patients per vaccine. PER AMENDMENT 3/20/96: The optimal dose of rgp120/HIV-1MN is 100 mcg and will be given to the 12 patients and the placebo will be given to 3. The optimal dose of rgp120/HIV-1SF2 is 5 mcg and will be given to the 12 patients and the placebo will be given to 3.

PER 2/3/95 AMENDMENT: After the initial patients are enrolled, 18 additional newborns will be randomized to one of the three dose levels of rgp120/HIV-1MN (with no placebos). PER AMENDMENT 6/5/95: Another group of 18 newborns will be randomized to one of three treatments representing 3 different doses of the Chiron/Biocine vaccine (with no placebos).

Eligibility criteria: Inclusion Criteria

Concurrent Medication:

Allowed:

* Antiretroviral therapy.
* Coenrollment in a therapeutic protocol if begun at least 30 days following the week 20 immunization.
* Routine immunizations if given more than 1 week before or after study vaccine.

Patients must be:

* \> 37 weeks gestation and \< 72 hours of age born to HIV-infected women.
* NOT born to women who received either passive or active immunotherapy during pregnancy.
* NOT breast-fed.
* NOT born to women who are hepatitis B surface antigen positive.
* Receiving AZT at study entry (except infants enrolled in ACTG 076).

NOTE:

* Parent or guardian must provide informed consent and be willing to comply with study requirements.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

* Documented or suspected serious bacterial infection, metabolic illness, or other immediate life-threatening conditions.

Concurrent Medication:

Excluded:

* Passive or active HIV-specific immunotherapy other than the study candidate vaccines.
* Investigational medications.

Primary outcomes:
measure: Development of adverse clinical, laboratory, or immunological responses to any of the recombinant vaccines
timeFrame: Throughout study
measure: Changes in viral load in infants found to be HIV infected
timeFrame: Throughout study
measure: Changes in the slope of absolute CD4 counts in all immunized children
timeFrame: Throughout study
Secondary outcomes:
measure: Changes in immune response to the vaccine candidates
timeFrame: Throughout study
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: UCLA-Los Angeles/Brazil AIDS Consortium (LABAC) CRS
state: California
city: San Diego
country: United States
facility: UCSD Maternal, Child, and Adolescent HIV CRS
state: California
city: San Francisco
country: United States
facility: San Francisco Gen. Hosp.
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: Aurora
country: United States
facility: Univ. of Colorado Denver NICHD CRS
state: Colorado
city: New Haven
country: United States
facility: Yale Univ. School of Medicine - Dept. of Peds., Div. of Infectious Disease
state: Connecticut
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: Chicago
country: United States
facility: Cook County Hosp.
state: Illinois
city: Chicago
country: United States
facility: Chicago Children's CRS
state: Illinois
city: Chicago
country: United States
facility: Univ. of Chicago - Dept. of Peds., Div. of Infectious Disease
state: Illinois
city: New Orleans
country: United States
facility: Tulane Univ. Health Science Ctr., Tulane Univ. Hosp. & Clinic
state: Louisiana
city: New Orleans
country: United States
facility: Tulane/LSU Maternal/Child CRS
state: Louisiana
city: Baltimore
country: United States
facility: Johns Hopkins Hosp. & Health System - Dept. of Peds., Div. of Infectious Diseases
state: Maryland
city: Boston
country: United States
facility: Brigham and Women's Hosp., Div. of Infectious Disease
state: Massachusetts
city: Boston
country: United States
facility: BMC, Div. of Ped Infectious Diseases
state: Massachusetts
city: Boston
country: United States
facility: HMS - Children's Hosp. Boston, Div. of Infectious Diseases
state: Massachusetts
city: Springfield
country: United States
facility: Baystate Health, Baystate Med. Ctr.
state: Massachusetts
city: Newark
country: United States
facility: NJ Med. School CRS
state: New Jersey
city: Paterson
country: United States
facility: St. Joseph's Hosp. & Med. Ctr. of New Jersey
state: New Jersey
city: Bronx
country: United States
facility: Bronx-Lebanon Hosp. IMPAACT CRS
state: New York
city: New York
country: United States
facility: NYU Med. Ctr., Dept. of Medicine
state: New York
city: New York
country: United States
facility: Columbia IMPAACT CRS
state: New York
city: New York
country: United States
facility: Incarnation Children's Ctr.
state: New York
city: Rochester
country: United States
facility: Strong Memorial Hospital Rochester NY NICHD CRS
state: New York
city: Rochester
country: United States
facility: Univ. of Rochester ACTG CRS
state: New York
city: Stony Brook
country: United States
facility: SUNY Stony Brook NICHD CRS
state: New York
city: Syracuse
country: United States
facility: SUNY Upstate Med. Univ., Dept. of Peds.
state: New York
city: Worcester
country: United States
facility: WNE Maternal Pediatric Adolescent AIDS CRS
state: New York
city: Durham
country: United States
facility: DUMC Ped. CRS
state: North Carolina
city: Philadelphia
country: United States
facility: The Children's Hosp. of Philadelphia IMPAACT CRS
state: Pennsylvania
city: Philadelphia
country: United States
facility: Univ. of Pennsylvania Health System, Hosp. of the Univ. of Pennsylvania
state: Pennsylvania
city: Houston
country: United States
facility: Texas Children's Hosp. CRS
state: Texas
city: Seattle
country: United States
facility: UW School of Medicine - CHRMC
state: Washington
city: San Juan
country: Puerto Rico
facility: San Juan City Hosp. PR NICHD CRS
Study officials:
affiliation: NYU MEDICAL CENTER
name: Borkowsky W
role: STUDY_CHAIR
affiliation: UCSF Moffit Hospital
name: Wara DW
role: STUDY_CHAIR
References:
citation: Rogers MF, Mofenson LM, Moseley RR. Reducing the risk of perinatal HIV transmission through zidovudine therapy: treatment recommendations and implications. J Am Med Womens Assoc (1972). 1995 May-Aug;50(3-4):78-82, 93.
citation: Cunningham CK, Wara DW, Kang M, Fenton T, Hawkins E, McNamara J, Mofenson L, Duliege AM, Francis D, McFarland EJ, Borkowsky W; Pediatric AIDS Clinical Trials Group 230 Collaborators. Safety of 2 recombinant human immunodeficiency virus type 1 (HIV-1) envelope vaccines in neonates born to HIV-1-infected women. Clin Infect Dis. 2001 Mar 1;32(5):801-7. doi: 10.1086/319215. Epub 2001 Feb 28.
citation: Borkowsky W, Wara D, Fenton T, McNamara J, Kang M, Mofenson L, McFarland E, Cunningham C, Duliege AM, Francis D, Bryson Y, Burchett S, Spector SA, Frenkel LM, Starr S, Van Dyke R, Jimenez E. Lymphoproliferative responses to recombinant HIV-1 envelope antigens in neonates and infants receiving gp120 vaccines. AIDS Clinical Trial Group 230 Collaborators. J Infect Dis. 2000 Mar;181(3):890-6. doi: 10.1086/315298.