A Phase I Study to Evaluate the Safety and Immunogenicity of Recombinant HIV-1 Envelope Antigen in Children Born to HIV-Infected Mothers

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.

Study Overview

• Status: Completed
• Conditions: HIV Infections; HIV Seronegativity
• Intervention / Treatment: Biological: rgp120/HIV-1MN; Biological: rgp120/HIV-1 SF-2; Biological: Placebo version of rgp120/HIV-1MN; Biological: Placebo version of rgp120/HIV-1SF2

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).

• Study Type: Interventional
• Enrollment (Actual): 156
• Phase: Phase 1

Contacts and Locations

Study Locations

• Puerto Rico
  • San Juan, Puerto Rico, 009367344
    • San Juan City Hosp. PR NICHD CRS
• United States
  • California
    • Long Beach, California, United States, 90801
      • Long Beach Memorial Med. Ctr., Miller Children's Hosp.
    • Los Angeles, California, United States, 900951752
      • UCLA-Los Angeles/Brazil AIDS Consortium (LABAC) CRS
    • San Diego, California, United States, 920930672
      • UCSD Maternal, Child, and Adolescent HIV CRS
    • San Francisco, California, United States, 941430105
      • UCSF Pediatric AIDS CRS
    • San Francisco, California, United States, 94110
      • San Francisco Gen. Hosp.
    • Torrance, California, United States, 905022004
      • Harbor - UCLA Med. Ctr. - Dept. of Peds., Div. of Infectious Diseases
  • Colorado
    • Aurora, Colorado, United States, 802181088
      • Univ. of Colorado Denver NICHD CRS
  • Connecticut
    • New Haven, Connecticut, United States, 06504
      • Yale Univ. School of Medicine - Dept. of Peds., Div. of Infectious Disease
  • Florida
    • Jacksonville, Florida, United States, 32209
      • Univ. of Florida Jacksonville NICHD CRS
    • Miami, Florida, United States, 33161
      • Univ. of Miami Ped. Perinatal HIV/AIDS CRS
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Cook County Hosp.
    • Chicago, Illinois, United States, 606143394
      • Chicago Children's CRS
    • Chicago, Illinois, United States, 606371470
      • Univ. of Chicago - Dept. of Peds., Div. of Infectious Disease
  • Louisiana
    • New Orleans, Louisiana, United States
      • Tulane/LSU Maternal/Child CRS
    • New Orleans, Louisiana, United States, 701122699
      • Tulane Univ. Health Science Ctr., Tulane Univ. Hosp. & Clinic
  • Maryland
    • Baltimore, Maryland, United States, 212874933
      • Johns Hopkins Hosp. & Health System - Dept. of Peds., Div. of Infectious Diseases
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • BMC, Div. of Ped Infectious Diseases
    • Boston, Massachusetts, United States
      • HMS - Children's Hosp. Boston, Div. of Infectious Diseases
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hosp., Div. of Infectious Disease
    • Springfield, Massachusetts, United States, 01199
      • Baystate Health, Baystate Med. Ctr.
  • New Jersey
    • Newark, New Jersey, United States, 07103
      • NJ Med. School CRS
    • Paterson, New Jersey, United States
      • St. Joseph's Hosp. & Med. Ctr. of New Jersey
  • New York
    • Bronx, New York, United States, 10457
      • Bronx-Lebanon Hosp. IMPAACT CRS
    • New York, New York, United States, 10032
      • Columbia IMPAACT CRS
    • New York, New York, United States, 10016
      • NYU Med. Ctr., Dept. of Medicine
    • New York, New York, United States, 10032
      • Incarnation Children's Ctr.
    • Rochester, New York, United States, 14642
      • Strong Memorial Hospital Rochester NY NICHD CRS
    • Rochester, New York, United States
      • Univ. of Rochester ACTG CRS
    • Stony Brook, New York, United States, 117948111
      • SUNY Stony Brook NICHD CRS
    • Syracuse, New York, United States, 13210
      • SUNY Upstate Med. Univ., Dept. of Peds.
    • Worcester, New York, United States
      • WNE Maternal Pediatric Adolescent AIDS CRS
  • North Carolina
    • Durham, North Carolina, United States, 277103499
      • DUMC Ped. CRS
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Univ. of Pennsylvania Health System, Hosp. of the Univ. of Pennsylvania
    • Philadelphia, Pennsylvania, United States, 191044318
      • The Children's Hosp. of Philadelphia IMPAACT CRS
  • Texas
    • Houston, Texas, United States, 77030
      • Texas Children's Hosp. CRS
  • Washington
    • Seattle, Washington, United States, 981050371
      • UW School of Medicine - CHRMC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 day to 3 days (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; Patients who will receive rgp120/HIV-1MN	Biological: rgp120/HIV-1MN; Administered at weeks 0, 4, 8, 12, and 20. Individual group assignment will determine specific dosage and schedule.
Experimental: 2; Patients who will receive rgp120/HIV-1SF2	Biological: rgp120/HIV-1 SF-2; Administered at weeks 0, 4, 8, 12, and 20. Individual group assignment will determine specific dosage and schedule.
Placebo Comparator: 3; Patients who will receive the placebo counterpart of 120/HIV-1MN	Biological: Placebo version of rgp120/HIV-1MN; Administered at weeks 0, 4, 8, 12, and 20. Individual group assignment will determine specific dosage and schedule.
Placebo Comparator: 4; Patients who will receive the placebo counterpart of rgp120/HIV-1SF2	Biological: Placebo version of rgp120/HIV-1SF2; Administered at weeks 0, 4, 8, 12, and 20. Individual group assignment will determine specific dosage and schedule.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Development of adverse clinical, laboratory, or immunological responses to any of the recombinant vaccines	Throughout study
Changes in viral load in infants found to be HIV infected	Throughout study
Changes in the slope of absolute CD4 counts in all immunized children	Throughout study

Secondary Outcome Measures

Outcome Measure	Time Frame
Changes in immune response to the vaccine candidates	Throughout study

Collaborators and Investigators

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Collaborators: Genentech, Inc.; Biocine
• Investigators: Study Chair: Borkowsky W, NYU Medical Center; Study Chair: Wara DW, UCSF Moffit Hospital

Publications and helpful links

General Publications

• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Completion (Actual): January 1, 1999

Study Registration Dates

• First Submitted: November 2, 1999
• First Submitted That Met QC Criteria: August 30, 2001
• First Posted (Estimate): August 31, 2001

Study Record Updates

• Last Update Posted (Actual): November 4, 2021
• Last Update Submitted That Met QC Criteria: October 27, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: Vaccines, Synthetic; AIDS Vaccines; HIV Preventive Vaccine; HIV Therapeutic Vaccine; HIV Envelope Protein gp120; Virus Replication
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections
• Other Study ID Numbers: ACTG 230; 11207 (Registry Identifier: DAIDS ES Registry Number)