A Phase 1 Clinical Trial to Evaluate the Immunogenicity of AIDSVAX B/E Bivalent gp120 Vaccine and MVA/HIV62B in Healthy, HIV-1-Uninfected Adult Participants Who Previously Received MVA/HIV62B in DNA/MVA or MVA/MVA Regimens in HVTN 205
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- HIV Infections
- Sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)
- Enrollment
- 27
- Locations
- 9
- Primary Endpoint
- Chemistry and Hematology Laboratory Measures, for Each Boost: Alkaline Phosphatase, AST, ALT in U/L
- Status
- Completed
- Last Updated
- 3 years ago
Overview
Brief Summary
The purpose of this study is to evaluate the safety, tolerability, and immunogenicity of the AIDSVAX B/E vaccine and the MVA/HIV62B vaccine in healthy, HIV-1-uninfected adults who previously received MVA/HIV62B in DNA/MVA or MVA/MVA vaccine regimens in the HVTN 205 study.
Detailed Description
This study will evaluate the safety, tolerability, and immunogenicity of the AIDSVAX B/E vaccine and the MVA/HIV62B vaccine in healthy, HIV-1-uninfected adults who previously received MVA/HIV62B in DNA/MVA or MVA/MVA vaccine regimens as part of the HVTN 205 study. Participants in this study will be assigned to one of five groups based on their previous vaccine regimen received in HVTN 205. Depending on their group, participants will receive the MVA/HIV62B vaccine, the AIDSVAX B/E vaccine, or both the MVA/HIV62B vaccine and the AIDSVAX B/E vaccine. All participants will receive their assigned vaccines at study entry (Day 0) and Month 4. Participants will attend several study visits through Month 10. Visits will include physical examinations, blood collection, HIV testing and risk reduction counseling, and interviews and questionnaires. Optional procedures at some visits include collection of rectal fluids, cervical fluids, and semen. Study staff will contact participants 2 years following the initial study injection for follow-up health monitoring.
Investigators
Eligibility Criteria
Inclusion Criteria
- •General and Demographic Criteria:
- •Age of 18 to 55 years
- •Prior participation in HVTN 205 with assignment to treatment (not placebo) arm:
- •Assigned to HVTN 205 Group 1 or Group 3, and received all 4 scheduled vaccinations (2 injections of pGA2/JS7 DNA (months 0, 2) and 2 injections of MVA/HIV62 (months 4, 6); OR
- •Assigned to HVTN 205 Group 4, and received at least vaccinations 1, 2 and 4 (3 injections of MVA/HIV62 at months 0, 2 and 6).
- •Access to a participating HVTN clinical research site (CRS) and willingness to be followed for the planned duration of the study
- •Ability and willingness to provide informed consent
- •Assessment of understanding: volunteer demonstrates understanding of this study; completes a questionnaire prior to first vaccination with verbal demonstration of understanding of all questionnaire items answered incorrectly
- •Willing to be contacted 2 years following initial study injection.
- •Agrees not to enroll in another study of an investigational research agent
Exclusion Criteria
- •Blood products received within 120 days before first vaccination
- •Investigational research agents received within 30 days before first vaccination
- •Body mass index (BMI) greater than or equal to 40
- •Volunteer has 2 or more of the following cardiac risk factors:
- •Participant report of history of elevated blood cholesterol defined as fasting LDL greater than 160 mg/dL;
- •First degree relative (eg, mother, father, brother, or sister) who had coronary artery disease before the age of 50 years;
- •Current smoker; or
- •BMI greater than or equal to 35
- •Pregnant or breastfeeding
- •Active duty and reserve U.S. military personnel
Outcomes
Primary Outcomes
Chemistry and Hematology Laboratory Measures, for Each Boost: Alkaline Phosphatase, AST, ALT in U/L
Time Frame: Measured during screening, and 2 weeks after each boost at Month 0 and 4
For each chemistry laboratory measure, summary statistics were presented by analyte and treatment group for the overall population.
Occurrence of Env-specific IgA Responses for gp120, gp41, V1V2, and the IDR of gp41 at 2 Weeks After Each Boost
Time Frame: Measured at Month 0.5 and 4.5
Serum HIV-1-specific IgA responses were measured on a Bio-Plex instrument using a standardized custom Luminex assay. The readout is background-subtracted mean fluorescent intensity (MFI), with background adjustment for an antigen-specific plate level control. For each sample, response magnitude is net MFI, defined as experimental antigen MFI minus reference antigen MFI. Net MFI less than 1 is set to 1. The measure unit fluorescence units are relative to assay background, not relative to the placebo arm. Background is used here rather than negative control stimulation, since the antigens are used as bead coating rather than stimulation. IgA responses to V1V2 and the IDR of gp41 were not assayed.
Level of Env-specific IgA Responses for gp120, gp41, V1V2, and the IDR of gp41 at 2 Weeks After Each Boost
Time Frame: Measured at Month 0.5 and 4.5
Serum HIV-1-specific IgA responses were measured on a Bio-Plex instrument using a standardized custom Luminex assay. The readout is background-subtracted mean fluorescent intensity (MFI), with background adjustment for an antigen-specific plate level control. For each sample, response magnitude is net MFI, defined as experimental antigen MFI minus reference antigen MFI. Net MFI less than 1 is set to 1. The measure unit fluorescence units are relative to assay background, not relative to the placebo arm. Background is used here rather than negative control stimulation, since the antigens are used as bead coating rather than stimulation. IgA responses to V1V2 and the IDR of gp41 were not assayed.
Number of Participants With Study Product Discontinuation Associated With an AE or Reactogenicity
Time Frame: Measured through the Month 4 boost
From the study product discontinuation form, study product administration reasons are tabulated by treatment arm
Chemistry and Hematology Laboratory Measures, for Each Boost: WBC, Platelets, Lymphocytes, Neutrophils
Time Frame: Measured during screening, and 2 weeks after each boost at Month 0 and 4
For each chemistry laboratory measure, summary statistics were presented by analyte and treatment group for the overall population.
Number of Participants Reporting Local Reactogenicity Signs and Symptoms of the Left Arm (MVA/HIV62B or Placebo)
Time Frame: Measured through 3 days after the boost at Month 0 and Month 4
Graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.0 \[November 2014\], The maximum grade observed for each symptom over the time frame is presented.
Number of Participants Reporting Local Reactogenicity Signs and Symptoms of the Right Arm (AIDSVAX B/E or Placebo)
Time Frame: Measured through 3 days after the boost at Month 0 and Month 4
Graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.0 \[November 2014\], The maximum grade observed for each symptom over the time frame is presented.
Number of Participants Reporting Systemic Reactogenicity Signs and Symptoms During the Boost Regimen
Time Frame: Measured through Month Measured through 3 days after each boost at Month 0 and 4
Graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.0 \[November 2014\], The maximum grade observed for each symptom over the time frame is presented.
Number of Participants With Early Study Termination Associated With an AE or Reactogenicity
Time Frame: Measured through Month 10
From the study termination form, early termination reasons associated with an AE or reactogenicity are tabulated by treatment arm
Occurrence of Env-specific IgG Responses for gp120, gp41, V1/V2, and the IDR of gp41 at 2 Weeks After Each Boost
Time Frame: Measured at Month 0.5 and 4.5
Serum HIV-1-specific IgG responses were measured on a Bio-Plex instrument using a standardized custom Luminex assay. The readout is background-subtracted mean fluorescent intensity (MFI), with background adjustment for an antigen-specific plate level control. For each sample, response magnitude is net MFI, defined as experimental antigen MFI minus reference antigen MFI. Net MFI less than 1 is set to 1. The measure unit fluorescence units are relative to assay background, not relative to the placebo arm. Background is used here rather than negative control stimulation, since the antigens are used as bead coating rather than stimulation. The responses to the IDR of gp41 was not assayed.
Level of Env-specific IgG Responses for gp120, gp41, V1/V2, and the IDR of gp41 at 2 Weeks After Each Boost
Time Frame: Measured at Month 0.5 and 4.5
Serum HIV-1-specific IgG responses were measured on a Bio-Plex instrument using a standardized custom Luminex assay. The readout is background-subtracted mean fluorescent intensity (MFI), with background adjustment for an antigen-specific plate level control. For each sample, response magnitude is net MFI, defined as experimental antigen MFI minus reference antigen MFI. Net MFI less than 1 is set to 1. The measure unit fluorescence units are relative to assay background, not relative to the placebo arm. Background is used here rather than negative control stimulation, since the antigens are used as bead coating rather than stimulation. The responses to the IDR of gp41 was not assayed.
Level of Env-specific IgG3 Responses for gp120, gp41, V1/V2, and the IDR of gp41 at 2 Weeks After Each Boost
Time Frame: Measured at Month 0.5 and 4.5
Serum HIV-1-specific IgG3 responses were measured on a Bio-Plex instrument using a standardized custom Luminex assay. The readout is background-subtracted mean fluorescent intensity (MFI), with background adjustment for an antigen-specific plate level control. For each sample, response magnitude is net MFI, defined as experimental antigen MFI minus reference antigen MFI. Net MFI less than 1 is set to 1. The measure unit fluorescence units are relative to assay background, not relative to the placebo arm. Background is used here rather than negative control stimulation, since the antigens are used as bead coating rather than stimulation. The responses to the IDR of gp41 was not assayed.
Occurrence of Neutralizing Ab Titers and Breadth Against the Env Vaccine Strain and Heterologous Tier 1 Strains at 2 Weeks After Each Boost
Time Frame: Measured at Month 0.5 and 4.5
Neutralizing antibodies against HIV-1 were measured as a function of reductions in Tat-regulated luciferase (Luc) reporter gene expression in TZM-bl cells. The assay measured neutralization titers against a panel of autologous and heterologous Env-pseudotyped viruses.
Chemistry and Hematology Laboratory Measures, for Each Boost: Hemoglobin, Creatinine in g/dL
Time Frame: Measured during screening, and 2 weeks after each boost at Month 0 and 4
For each chemistry laboratory measure, summary statistics were presented by analyte and treatment group for the overall population.
Occurrence of Env-specific IgG3 Responses for gp120, gp41, V1/V2, and the IDR of gp41 at 2 Weeks After Each Boost
Time Frame: Measured at Month 0.5 and 4.5
Serum HIV-1-specific IgG3 responses were measured on a Bio-Plex instrument using a standardized custom Luminex assay. The readout is background-subtracted mean fluorescent intensity (MFI), with background adjustment for an antigen-specific plate level control. For each sample, response magnitude is net MFI, defined as experimental antigen MFI minus reference antigen MFI. Net MFI less than 1 is set to 1. The measure unit fluorescence units are relative to assay background, not relative to the placebo arm. Background is used here rather than negative control stimulation, since the antigens are used as bead coating rather than stimulation. The responses to the IDR of gp41 was not assayed.
Level of Neutralizing Ab Titers and Breadth Against the Env Vaccine Strain and Heterologous Tier 1 Strains at 2 Weeks After Each Boost
Time Frame: Measured at Month 0.5 and 4.5
Neutralizing antibodies against HIV-1 were measured as a function of reductions in Tat-regulated luciferase (Luc) reporter gene expression in TZM-bl cells. The assay measured neutralization titers against a panel of autologous and heterologous Env-pseudotyped viruses. A serum neutralization titer was defined as the serum dilution that reduced relative luminescence units (RLUs) by 50% (ID50) relative to the RLUs in virus control wells (cells + virus only) after subtraction of background RLU (cells only). Titer \< 10 is truncated at 5.
Secondary Outcomes
- Occurrence of CD4+ T Cell Responses to the HIV Proteins Included in the Vaccine 2 Weeks After Each Boost(Measured at Month 4.5)
- Level of CD4+ T Cell Responses to the HIV Proteins Included in the Vaccine 2 Weeks After Each Boost(Measured at Month 4.5)
- Level of CD8+ T Cell Responses to the HIV Proteins Included in the Vaccine 2 Weeks After Each Boost(Measured at Month 4.5)
- Occurrence of CD8+ T Cell Responses to the HIV Proteins Included in the Vaccine 2 Weeks After Each Boost(Measured at Month 4.5)
- Occurrence of Env-specific IgG Responses for gp120, gp140, V1/V2, and the IDR of gp41 at 6 Months After the Final Boost(Measured at Month 10)
- Level of Env-specific IgG Responses for gp120, gp41, V1/V2, and the IDR of gp41 at 6 Months After the Final Boost(Measured at Month 10)