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

Study Overview
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Brief Summary
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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
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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).

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

Conditions
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HIV Infections, HIV Seronegativity

Intervention / Treatment
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* Biological: rgp120/HIV-1MN
* Biological: rgp120/HIV-1 SF-2
* Biological: Placebo version of rgp120/HIV-1MN
* Biological: Placebo version of rgp120/HIV-1SF2


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 1 Day
Maximum Age: 3 Days

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Vaccines, Synthetic, Virus Replication, HIV Envelope Protein gp120, AIDS Vaccines, HIV Preventive Vaccine, HIV Therapeutic Vaccine