A Phase 1 Double-Blind, Randomized Clinical Trial to Evaluate the Safety and Immunogenicity of a Recombinant Oligomeric gp145 Clade C Env Protein (gp145 C.6980) in Healthy, HIV-1-Uninfected Adult Participants in the US
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- HIV Infections
- Sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)
- Enrollment
- 45
- Locations
- 3
- Primary Endpoint
- Number of Participants Reporting Local Reactogenicity Signs and Symptoms: Pain and/or Tenderness
- Status
- Completed
- Last Updated
- 4 years ago
Overview
Brief Summary
The purpose of this study is to evaluate the safety, tolerability, and immunogenicity of an HIV vaccine (gp145 C.6980) with aluminum hydroxide adjuvant in healthy, HIV-1-uninfected adults in the United States.
Detailed Description
This study will evaluate the safety, tolerability, and immunogenicity of an HIV vaccine (gp145 C.6980) with aluminum hydroxide adjuvant in healthy, HIV-1-uninfected adults in the United States. Participants will be randomly assigned to one of three groups. Participants in Group 1 will receive 300 mcg of gp145 C.6980 and aluminum hydroxide adjuvant on Day 0 and Months 2 and 6. Participants in Group 2 will receive 100 mcg of gp145 C.6980 and aluminum hydroxide adjuvant on Day 0 and Months 2 and 6. Participants in Group 3 will receive placebo on Day 0 and Months 2 and 6. Study visits will occur at Day 0 (study entry), Weeks 1 and 2, and Months 2, 2.5, 6, 6.25, 6.5, 9, and 12. Visits may include physical examinations, blood and urine collection, HIV testing, risk reduction counseling, and questionnaires.
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 and completes a questionnaire prior to first vaccination with verbal demonstration of understanding of all questionnaire items initially answered incorrectly
- •Agrees not to enroll in another study of an investigational research agent before the last scheduled protocol clinic visit
- •Good general health as shown by medical history, physical exam, and screening laboratory tests
- •HIV-Related Criteria:
- •Willingness to receive HIV test results
- •Willingness to discuss HIV infection risks and amenable to HIV risk reduction counseling.
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 122 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 122 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 122 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 122 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 122 PSRT on a case-by-case basis.
- •Live attenuated vaccines other than influenza vaccine received within 30 days before or scheduled and intended to be received within 14 days after the first vaccination (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: Pain and/or Tenderness
Time Frame: Measured through 7 days after first vaccination at Month 0
Graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events. Corrected Version 2.1, dated July 2017. The maximum grade observed for each symptom over the time frame is presented.
Number of Participants Reporting Local Reactogenicity Signs and Symptoms：Erythema and/or Induration
Time Frame: Measured through 7 days after first vaccination at Month 0
Graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events. Corrected Version 2.1, dated 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 7 days after first vaccination at Month 0
Graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events. Corrected Version 2.1, dated July 2017. The following symptoms are considered as systemic reactogenicity if the onset date was within the periods of assessment specified in the protocol: malaise and/or fatigue, myalgia, headache, nausea, vomiting, chills, arthralgia, and body temperature. The item Max. Systemic Reaction is the maximum of the individual systemic variables for a participant. It does not include temperature.
Number of Participants Reporting Adverse Events (AEs), by Severity Grade
Time Frame: Measured through 30 days after first vaccination at Month 0
Severity definitions are found in The Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Corrected Version 2.1, dated July 2017); 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 30 days after first vaccination at Month 0
Measured as outlined in Version 2.0 (January 2010) of the Manual for Expedited Reporting of Adverse Events to DAIDS (DAIDS EAE Manual)
Chemistry and Hematology Laboratory Measures With Grade 1 or Higher, Through First Vaccination
Time Frame: Measured at 2 weeks after first vaccination
Laboratory results are summarized by analyte and timepoint. Analytes and timepoint combinations with grade 1 or higher results are shown.
Number of Participants Reporting Adverse Events (AEs), by Relationship to Study Product
Time Frame: Measured through 30 days after first vaccination at Month 0
Severity definitions are found in The Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Corrected Version 2.1, dated July 2017); For participants reporting multiple AEs over the time frame, the maximum severity grade is counted.
Chemistry Laboratory Measures: Hemoglobin, Creatinine
Time Frame: Measured at 2 weeks after first vaccination
For each chemistry laboratory measure, summary statistics were presented by analyte and treatment group for the overall population.
Chemistry Laboratory Measures: ALT
Time Frame: Measured at 2 weeks after first vaccination
For each chemistry laboratory measure, summary statistics were presented by analyte and treatment group for the overall population.
Hematology Laboratory Measures: WBC, Neutrophils , Lymphocytes and Platelets
Time Frame: Measured at 2 weeks after first vaccination
For each chemistry laboratory measure, summary statistics were presented by analyte and treatment group for the overall population.
Secondary Outcomes
- Number of Participants Reporting Local Reactogenicity Signs and Symptoms：Erythema and/or Induration(Measured through Month 6.5)
- Chemistry and Hematology Laboratory Results With Grade 1 or Higher, Through All Vaccinations(Measured during Screening, Month 0.5, 2.5, 6.5 and 9)
- Hematology Laboratory Measures: WBC, Platelets, Lymphocytes, Neutrophils , Through All Vaccinations(Measured during Screening, Month 0.5, 2.5, 6.5 and 9)
- Chemistry Laboratory Measures: ALT, Through All Vaccinations(Measured during Screening, Month 0.5, 2.5, 6.5 and 9)
- Number of Participants Reporting Local Reactogenicity Signs and Symptoms: Pain and/or Tenderness(Measured through Month 6.5)
- Number of Participants Reporting Adverse Events (AEs), by Relationship to Study Product(Measured through Month 7)
- Number of Participants Reporting Adverse Events (AEs), by Severity Grade(Measured through Month 7)
- Level of Vaccine-induced Binding Antibodies to HIV Proteins Measured by the Binding Antibody Multiplex Assay (BAMA)(Measured at 2 weeks after the third vaccination)
- Level of Neutralizing Antibody Responses Against HIV-1 Isolates(Measured at 2 weeks after the third vaccination)
- Chemistry Laboratory Measures: Hemoglobin, Creatinine, Through All Vaccinations(Measured during Screening, Month 0.5, 2.5, 6.5 and 9)
- Number of Participants Reporting Systemic Reactogenicity Signs and Symptoms(Measured through Month 6.5)
- Frequency of Serious Adverse Events (SAEs)(Measured through Month 12)
- Occurrence of Vaccine-induced Binding Antibodies to HIV Proteins Measured by the Binding Antibody Multiplex Assay (BAMA)(Measured at 2 weeks after the third vaccination)
- Occurrence of HIV-specific CD4+ and CD8+ T-cell Responses to the HIV Proteins Included in the Vaccine. Measured by Flow Cytometry.(Measured at 2 weeks after the third vaccination)
- Levels of CD4+ and CD8+ T Cells Responses to the HIV Proteins Included in the Vaccine. Measured by Flow Cytometry.(Measured at 2 weeks after the third vaccination)
- Occurrence of Neutralizing Antibody Responses Against HIV-1 Isolates(Measured at 2 weeks after the third vaccination)