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 HIV-1 Vaccines (PDPHV-201401) Co-administered With or Without Adjuvant GLA-SE in Repeated Doses, in Healthy, HIV-1 Uninfected Adult Participants
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- HIV Infections
- Sponsor
- Worcester HIV Vaccine
- Enrollment
- 42
- Locations
- 1
- Primary Endpoint
- Frequency of local injection site (including DTH) reactogenicity signs and symptoms
- Status
- Completed
- Last Updated
- 2 years ago
Overview
Brief Summary
The purpose of the study is to evaluate the safety, tolerability, and immunogenicity of polyvalent env (A,B,C,A/E)/gag (C) DNA and gp120 (A,B,C,A/E) protein vaccines (PDPHV201401) co-administered together with or without adjuvant in repeated doses in healthy, HIV-uninfected adults
Detailed Description
The purpose of the study is to evaluate the safety, tolerability, and immunogenicity of polyvalent env (A,B,C,A/E)/gag (C) DNA and gp120 (A,B,C,A/E) protein vaccines (PDPHV201401) co-administered together with or without adjuvant in repeated doses in healthy, HIV-uninfected adults. Participants will be enrolled in either Group 1 or 2 with Group 1 being enrolled first to compensate for the longer duration of vaccination period. Within each group, participants will be randomly assigned to either Treatment or Control. Participants in Group 1 (Treatment) will receive polyvalent env (A,B,C,A/E)/gag (C) DNA vaccine in one arm and polyvalent gp120 (A,B,C,A/E) protein vaccine mixed with GLA-SE adjuvant in the other arm on Day 0 and at Months 3, 6, and 12. Participants in Group 1 (Control) will receive placebo on Day 0 and at Months 3, 6, and 12. Participants in Group 2 (Treatment) will receive a mixture of polyvalent env (A,B,C,A/E)/gag (C) DNA vaccine and polyvalent gp120 (A,B,C,A/E) protein vaccine (without GLA-SE adjuvant) divided into two doses and administered into each arm on Day 0 and at Months 1, 3, 6, and 8. Participants in Group 2 (Control) will receive placebo on Day 0 and at Months 1, 3, 6, and 8. Study visits for participants in Group 1 will occur on Day 0, Week 2, Months 3, 3.5, 6, 6.5, 12, 12 + 1 Week, 12.5, 18, and 24. Study visits for participants in Group 2 will occur on Day 0, Week 2, Months 1, 1.5, 3, 3.5, 6, 6.5, 8, 8 + 1 Week, 8.5, 14, and 20. Visits may include physical examination, blood and urine collection, HIV testing, risk reduction counseling, and questionnaires.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Age of 18 to 50 years
- •Access to BWH trial site 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
- •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
- •Willingness to receive HIV test results
- •Willingness to discuss HIV infection risks and amenable to HIV risk reduction counseling.
- •Assessed by the clinic staff as being at "low risk" for HIV infection and committed to maintaining behavior consistent with low risk of HIV exposure through the last required protocol clinic visit. HVTN low risk guidelines will be used.
- •Laboratory Inclusion Values Hemogram/CBC
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) ≥ 40; or BMI ≥ 35 with 2 or more of the following: age \> 45, systolic blood pressure \> 140 mm Hg, diastolic blood pressure \> 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
- •Pregnant or breastfeeding
- •Active duty and reserve US military personnel Vaccines and other Injections
- •HIV vaccine(s) received in a prior HIV vaccine trial.
- •Non-HIV experimental vaccine(s) received within the last 5 years in a prior vaccine trial, unless the vaccine subsequently received regulatory approval or emergency authorization.
- •Live attenuated vaccines, other than influenza vaccine, 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)
- •Any vaccines that are not live attenuated vaccines and were received within 14 days prior to first vaccination (eg, tetanus, pneumococcal, Hepatitis A or B)
Outcomes
Primary Outcomes
Frequency of local injection site (including DTH) reactogenicity signs and symptoms
Time Frame: Measured through participants' last study visit, at Month 20 to 24, depending on which part of the study participants are enrolled in
Graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017
Frequency of systemic reactogenicity signs and symptoms
Time Frame: Measured through participants' last study visit, at Month 20 to 24, depending on which part of the study participants are enrolled in
Graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017
Frequency of adverse events (AEs)
Time Frame: Measured through participants' last study visit, at Month 20 to 24, depending on which part of the study participants are enrolled in
AEs categorized by Medical Dictionary for Regulatory Activities (MedDRA) system organ class, MedDRA preferred term, severity, and assessed relationship to study products
Number of participants with early discontinuation of vaccinations
Time Frame: Measured through participants' last study visit, at Month 20 to 24, depending on which part of the study participants are enrolled in
Tabulated by reason and treatment arm
Severity of local injection site (including DTH) reactogenicity signs and symptoms
Time Frame: Measured through participants' last study visit, at Month 20 to 24, depending on which part of the study participants are enrolled in
Graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017
Severity of adverse events (AEs)
Time Frame: Measured through participants' last study visit, at Month 20 to 24, depending on which part of the study participants are enrolled in
AEs categorized by MedDRA system organ class, MedDRA preferred term, severity, and assessed relationship to study products
Severity of systemic reactogenicity signs and symptoms
Time Frame: Measured through participants' last study visit, at Month 20 to 24, depending on which part of the study participants are enrolled in
Graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017
Secondary Outcomes
- Serum neutralizing antibody responses against Tier 1A, Tier 1B, and selected Tier 2 viruses(Measured at 2 weeks after the last vaccination)
- Frequency of HIV-1 specific CD4+ and CD8+ T-cell responses(Measured at 2 weeks after the last vaccination)
- Magnitude of serum HIV-1 Env-specific IgG responses(Measured at 2 weeks after the last vaccination)
- Breadth of gp70-V1V2 IgG and gp120 IgA(Measured at 2 weeks after the last vaccination)