A Phase 1 Clinical Trial to Evaluate the Safety and Immunogenicity of Polyvalent Env (A,B,C,A/E) / Gag (C) DNA and gp120 (A,B,C,A/E) Protein/GLA-SE HIV-1 Vaccines (PDPHV-201401) as a Prime-boost Regimen or Co-administered in Repeated Doses, in Healthy, HIV-1-Uninfected Adult Participants
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- HIV Infections
- Sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)
- Enrollment
- 60
- Locations
- 6
- Primary Endpoint
- Number of Participants Reporting Local Reactogenicity Signs and Symptoms
- Status
- Completed
- Last Updated
- 4 years ago
Overview
Brief Summary
The purpose of this study is to evaluate the safety, tolerability, and immunogenicity of env (A,B,C,A/E)/gag (C) DNA and gp120 (A,B,C,A/E) protein/GLA-SE HIV-1 vaccines (PDPHV-201401) as a prime-boost regimen or co-administered in repeated doses, in healthy, HIV-1-uninfected adults.
Detailed Description
This study will evaluate the safety, tolerability, and immunogenicity of env (A,B,C,A/E)/gag (C) DNA and gp120 (A,B,C,A/E) protein/GLA-SE HIV-1 vaccines (PDPHV-201401) as a prime-boost regimen or co-administered in repeated doses, in healthy, HIV-1-uninfected adults. The study will be conducted in two parts (Part A and Part B). Participants in Part A will be randomly assigned to either Group 1 (Treatment) or Group 1 (Control). Participants in Group 1 (Treatment) will receive the gp120 (A,B,C,A/E) protein vaccine admixed with GLA-SE adjuvant on Day 0 and Month 2. Participants in Group 1 (Control) will receive placebo on Day 0 and Month 2. Researchers will evaluate study data from Part A before enrolling participants in Part B. Participants in Part B will be enrolled in either Groups 2 or 3. Within Group 2, participants will be randomly assigned to either Group 2 (Treatment) or Group 2 (Control). Participants in Group 2 (Treatment) will receive the env (A,B,C,A/E)/gag (C) DNA vaccine and placebo on Day 0 and Months 1 and 3. At Months 6 and 8, participants will receive the gp120 (A,B,C,A/E) protein vaccine admixed with GLA-SE adjuvant and a placebo vaccine. Participants in Group 2 (Control) will receive placebo on Day 0 and Months 1, 3, 6, and 8. Participants in Group 3 will be randomly assigned to either Group 3 (Treatment) or Group 3 (Control). Participants in Group 3 (Treatment) will receive the env (A,B,C,A/E)/gag (C) DNA vaccine and the gp120 (A,B,C,A/E) protein vaccine admixed with GLA-SE adjuvant on Day 0 and Months 1, 3, 6, and 8. Participants in Group 3 (Control) will receive placebo on Day 0 and Months 1, 3, 6, and 8. Study visits for participants in Part A will occur on Day 0, Week 2, and Months 2, 2.5, 5, and 8. Study visits for participants in Part B will occur on Day 0, Week 2, and Months 1, 1.5, 3, 3.5, 6, 6.5, 8, 8 + 1 Week, 8.5, 11, and 14. Visits may include physical examinations, blood and urine collection, HIV testing, risk reduction counseling, and questionnaires. Participants in Part B may also have optional saliva, semen, cervical fluid, rectal fluid, and stool sample collection. Study staff will contact all participants 12 months after the last vaccination for follow-up health monitoring.
Investigators
Eligibility Criteria
Inclusion Criteria
- •General and Demographic Criteria
- •Age of 18 to 50 years
- •Access to a participating HIV Vaccine Trials Network (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 12 months after the last vaccination
- •Agrees not to enroll in another study of an investigational research agent
- •Good general health as shown by medical history, physical exam, and screening laboratory tests
- •HIV-Related Criteria:
- •Willingness to receive HIV test results
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; or BMI greater than or equal to 35 with 2 or more of the following: age greater than 45, systolic blood pressure greater than 140 mm Hg, diastolic blood pressure greater than 90 mm Hg, current smoker, known hyperlipidemia
- •Intent to participate in another study of an investigational research agent or any other study that requires non-HVTN HIV antibody testing during the planned duration of the HVTN 124 study
- •Pregnant or breastfeeding
- •Active duty and reserve US military personnel
- •Vaccines and other Injections
- •HIV vaccine(s) received in a prior HIV vaccine trial. For volunteers who have received control/placebo in an HIV vaccine trial, the HVTN 124 PSRT will determine eligibility on a case-by-case basis.
- •Non-HIV experimental vaccine(s) received within the last 5 years in a prior vaccine trial. Exceptions may be made by the HVTN 124 PSRT for vaccines that have subsequently undergone licensure by the FDA. For volunteers who have received control/placebo in an experimental vaccine trial, the HVTN 124 PSRT will determine eligibility on a case-by-case basis. For volunteers who have received an experimental vaccine(s) greater than 5 years ago, eligibility for enrollment will be determined by the HVTN 124 PSRT on a case-by-case basis.
- •Live attenuated vaccines received within 30 days before first vaccination or scheduled within 14 days after injection (eg, measles, mumps, and rubella \[MMR\]; oral polio vaccine \[OPV\]; varicella; yellow fever)
Outcomes
Primary Outcomes
Number of Participants Reporting Local Reactogenicity Signs and Symptoms
Time Frame: Measured through 3 days after participants' each vaccination at Months 0, 2 for part A and Months 0, 1, 3, 6, 8 for part B
Graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017. The maximum grade observed for each symptom over the time frame is presented.
Number of Participants Reporting Systemic Reactogenicity Signs and Symptoms
Time Frame: Measured through 3 days after participants' each vaccination at Months 0, 2 for part A and Months 0, 1, 3, 6, 8 for part B
Graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017. The maximum grade observed for each symptom over the time frame is presented.
Number of Participants Reporting Adverse Events (AEs), by Relationship to Study Product
Time Frame: Measured through 30 days after each vaccine dose at Months 0, 2 for part A and Months 0, 1, 3, 6, 8 for part B
For participants reporting multiple AEs over the time frame, the maximum relationship is counted.
Number of Participants Reporting Adverse Events (AEs), by Severity Grade
Time Frame: Measured through 30 days after each vaccine dose at Months 0, 2 for part A and Months 0, 1, 3, 6, 8 for part B
For participants reporting multiple AEs over the time frame, the maximum severity grade is counted.
Number of Participants Reporting Serious Adverse Events (SAEs)
Time Frame: Measured through Month 8 for part A and Month 14 for part B
Measured as outlined in Version 2.0 (January 2010) of the Manual for Expedited Reporting of Adverse Events to DAIDS (DAIDS EAE Manual).
Number of Participants Reporting Adverse Events of Special Interest (AESIs)
Time Frame: Measured through Month 8 for part A and Month 14 for part B
Adverse events of special interest were described in Appendix N of the protocol. AESI for this protocol include but are not limited to potential immune-mediated diseases. There were no adverse events of special interest reported by any participant.
Numbers of Participants With Grade 1 or Higher Local Laboratory Results
Time Frame: Measured during Screening, Day 14, Day 70, Day140 for part A and visits Screening, Day 14, Day 42, Day 98, Day 182, Day 238 and Day 334 for part B
The number (percentage) of participants with local laboratory values recorded as meeting Grade 1 AE criteria or above as specified in the DAIDS AE Grading Table were tabulated by treatment arm for each post-vaccination time point. Laboratory results are summarized by analyte and timepoint. Analytes and timepoint combinations with no grade 1 or higher results are not shown.
Alk Phos, AST, ALT in UL
Time Frame: Measured through Screening, Day 14, Day 70, Day140 for part A and visits Screening, Day 14, Day 42, Day 98, Day 182, Day 238 and Day 334 for part B
Laboratory results are summarized by analyte and timepoint.
Hemoglobin, Creatinine in g/dL
Time Frame: Measured through Screening, Day 14, Day 70, Day140 for part A and visits Screening, Day 14, Day 42, Day 98, Day 182, Day 238 and Day 334 for part B
Laboratory results are summarized by analyte and timepoint.
WBC, Platelets, Lymphocytes, Neutrophils in Thousand Cells/Cubic mm
Time Frame: Measured through Screening, Day 14, Day 70, Day140 for part A and visits Screening, Day 14, Day 42, Day 98, Day 182, Day 238 and Day 334 for part B
Laboratory results are summarized by analyte and timepoint.
Number of Participants With Early Discontinuation of Vaccinations and Reason for Discontinuation
Time Frame: Measured through study completion, up to 31 months
From the study product discontinuation form, study product administration reasons are tabulated by treatment arm
Secondary Outcomes
- Occurrence of IgG HIV-1 Env-specific IgG Responses Two Weeks After the Last Vaccination(Measured at Month 2.5 for part A and 8.5 for part B)
- Levels of IgG HIV-1 Env-specific IgG Responses Two Weeks After the Last Vaccination(Measured at Month 2.5 for part A and 8.5 for part B)
- Breadth of IgG HIV-1 Env-specific IgG Responses Two Weeks After the Last Vaccination(Measured at Month 2.5 for part A and 8.5 for part B)
- Part B: Occurrence of Serum Neutralizing Antibody Responses Against Tier 1A, Tier 1B, and Selected Tier 2 Viruses Two Weeks After the Last Vaccination(Measured at Month 8.5 for part B only)
- Part B: Levels of Serum Neutralizing Antibody Responses Against Tier 1A, Tier 1B, and Selected Tier 2 Viruses Two Weeks After the Last Vaccination(Measured at Month 8.5 for part B only)
- Breadth of gp70-V1V2 IgG and gp120 IgA, Assessed by Binding Antibody Multiplex Assay, and ADCC Activities Against HIV-1 Subtypes A, B, C and A/E Two Weeks After the Last Vaccination in Part B(Measured at Month 8.5 for part B only)
- Occurrence of CD4+ T Cell Responses to the HIV Proteins Included in the Vaccine Two Weeks After the Last Vaccination. Measured by Flow Cytometry.(Measured at Month 8.5 for part B only)
- Level of CD4+ T Cell Responses to the HIV Proteins Included in the Vaccine Two Weeks After the Last Vaccination. Measured by Flow Cytometry.(Measured at Month 8.5 for part B only)
- Occurrence of CD8+ T Cell Responses to the HIV Proteins Included in the Vaccine Two Weeks After the Last Vaccination. Measured by Flow Cytometry.(Measured at Month 8.5 for part B only)
- Level of CD8+ T Cell Responses to the HIV Proteins Included in the Vaccine Two Weeks After the Last Vaccination. Measured by Flow Cytometry.(Measured at Month 8.5 for part B only)