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

This study has been completed.
Sponsor:
Collaborators:
Genentech
Biocine
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00000774
First received: November 2, 1999
Last updated: May 22, 2012
Last verified: May 2012
  Purpose

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.


Condition Intervention Phase
HIV Infections
HIV Seronegativity
Biological: rgp120/HIV-1MN
Biological: rgp120/HIV-1 SF-2
Biological: Placebo version of rgp120/HIV-1MN
Biological: Placebo version of rgp120/HIV-1SF2
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:
  • Development of adverse clinical, laboratory, or immunological responses to any of the recombinant vaccines [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
  • Changes in viral load in infants found to be HIV infected [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  • Changes in the slope of absolute CD4 counts in all immunized children [ Time Frame: Throughout study ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Changes in immune response to the vaccine candidates [ Time Frame: Throughout study ] [ Designated as safety issue: No ]

Enrollment: 156
Study Completion Date: January 1999
Arms Assigned Interventions
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.

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

Ages Eligible for Study:   up to 3 Days
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00000774

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

Publications:
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00000774     History of Changes
Other Study ID Numbers: ACTG 230, 11207
Study First Received: November 2, 1999
Last Updated: May 22, 2012
Health Authority: United States: Federal Government
United States: Food and Drug Administration

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Vaccines, Synthetic
Virus Replication
HIV Envelope Protein gp120
AIDS Vaccines
HIV Preventive Vaccine
HIV Therapeutic Vaccine

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases

ClinicalTrials.gov processed this record on April 15, 2014