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

HIV Infections Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00000774
• Other study ID #: ACTG 230
• Secondary ID: 11207
• Status: Completed
• Phase: Phase 1
• Est. completion date: January 1999

Study information

• Verified date: October 2021
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 156
• Est. completion date: January 1999
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: N/A to 3 Days

Eligibility

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.

Related Conditions & MeSH terms

• HIV Infections
• HIV Seronegativity

Intervention

Biological:
• rgp120/HIV-1MN
Administered at weeks 0, 4, 8, 12, and 20. Individual group assignment will determine specific dosage and schedule.
• rgp120/HIV-1 SF-2
Administered at weeks 0, 4, 8, 12, and 20. Individual group assignment will determine specific dosage and schedule.
• 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 version of rgp120/HIV-1SF2
Administered at weeks 0, 4, 8, 12, and 20. Individual group assignment will determine specific dosage and schedule.

Locations

Country	Name	City	State
Puerto Rico	San Juan City Hosp. PR NICHD CRS	San Juan
United States	Univ. of Colorado Denver NICHD CRS	Aurora	Colorado
United States	Johns Hopkins Hosp. & Health System - Dept. of Peds., Div. of Infectious Diseases	Baltimore	Maryland
United States	BMC, Div. of Ped Infectious Diseases	Boston	Massachusetts
United States	Brigham and Women's Hosp., Div. of Infectious Disease	Boston	Massachusetts
United States	HMS - Children's Hosp. Boston, Div. of Infectious Diseases	Boston	Massachusetts
United States	Bronx-Lebanon Hosp. IMPAACT CRS	Bronx	New York
United States	Chicago Children's CRS	Chicago	Illinois
United States	Cook County Hosp.	Chicago	Illinois
United States	Univ. of Chicago - Dept. of Peds., Div. of Infectious Disease	Chicago	Illinois
United States	DUMC Ped. CRS	Durham	North Carolina
United States	Texas Children's Hosp. CRS	Houston	Texas
United States	Univ. of Florida Jacksonville NICHD CRS	Jacksonville	Florida
United States	Long Beach Memorial Med. Ctr., Miller Children's Hosp.	Long Beach	California
United States	UCLA-Los Angeles/Brazil AIDS Consortium (LABAC) CRS	Los Angeles	California
United States	Univ. of Miami Ped. Perinatal HIV/AIDS CRS	Miami	Florida
United States	Yale Univ. School of Medicine - Dept. of Peds., Div. of Infectious Disease	New Haven	Connecticut
United States	Tulane Univ. Health Science Ctr., Tulane Univ. Hosp. & Clinic	New Orleans	Louisiana
United States	Tulane/LSU Maternal/Child CRS	New Orleans	Louisiana
United States	Columbia IMPAACT CRS	New York	New York
United States	Incarnation Children's Ctr.	New York	New York
United States	NYU Med. Ctr., Dept. of Medicine	New York	New York
United States	NJ Med. School CRS	Newark	New Jersey
United States	St. Joseph's Hosp. & Med. Ctr. of New Jersey	Paterson	New Jersey
United States	The Children's Hosp. of Philadelphia IMPAACT CRS	Philadelphia	Pennsylvania
United States	Univ. of Pennsylvania Health System, Hosp. of the Univ. of Pennsylvania	Philadelphia	Pennsylvania
United States	Strong Memorial Hospital Rochester NY NICHD CRS	Rochester	New York
United States	Univ. of Rochester ACTG CRS	Rochester	New York
United States	UCSD Maternal, Child, and Adolescent HIV CRS	San Diego	California
United States	San Francisco Gen. Hosp.	San Francisco	California
United States	UCSF Pediatric AIDS CRS	San Francisco	California
United States	UW School of Medicine - CHRMC	Seattle	Washington
United States	Baystate Health, Baystate Med. Ctr.	Springfield	Massachusetts
United States	SUNY Stony Brook NICHD CRS	Stony Brook	New York
United States	SUNY Upstate Med. Univ., Dept. of Peds.	Syracuse	New York
United States	Harbor - UCLA Med. Ctr. - Dept. of Peds., Div. of Infectious Diseases	Torrance	California
United States	WNE Maternal Pediatric Adolescent AIDS CRS	Worcester	New York

Sponsors (3)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)	Biocine, Genentech, Inc.

Countries where clinical trial is conducted

United States,  Puerto Rico, 

References & Publications (3)

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. — View 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. Epub 2001 Feb 28. — View 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. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Development of adverse clinical, laboratory, or immunological responses to any of the recombinant vaccines		Throughout study
Primary	Changes in viral load in infants found to be HIV infected		Throughout study
Primary	Changes in the slope of absolute CD4 counts in all immunized children		Throughout study
Secondary	Changes in immune response to the vaccine candidates		Throughout study