A Phase 1 Clinical Trial to Evaluate the Safety and Immunogenicity of Heterologous Prime-Boost Regimens Utilizing Recombinant Adenovirus Serotype 35 (rAd35) With HIV-1 Clade A Env Insert and Recombinant Adenovirus Serotype 5 (rAd5) With HIV-1 Clade A or B Env Inserts in Healthy, HIV-1-Uninfected Adults
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- HIV Infections
- Sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)
- Enrollment
- 180
- Locations
- 8
- Primary Endpoint
- Frequency of adverse events (AEs) categorized by MedDRA body system, MedDRA preferred term, severity and assessed relationship to study products; detailed description of all AEs meeting DAIDS criteria for expedited reporting
- Status
- Completed
- Last Updated
- 4 years ago
Overview
Brief Summary
The purpose of this study is to evaluate the safety and immune response of an adenovirus-based HIV-1 vaccine regimen that includes two vaccines given at different time points in HIV-uninfected adults.
Detailed Description
One approach to developing a preventive HIV vaccine includes the use of a prime-boost vaccine strategy. This type of strategy involves two vaccines, given sequentially at different time points. The goal is to stimulate different parts of the immune system and enhance the body's overall immune response to HIV. In this study, participants will receive two HIV vaccines 3 months apart. Heterologous-insert prime-boost vaccine regimens, which use the same gene from different HIV-1 subtypes, may be more effective than traditional homologous insert prime-boost vaccine regimens at eliciting immune responses directed at epitopes that are highly prevalent, possibly leading to a more effective immune system response to the vaccine. The purpose of this study is to assess the safety and immunogenicity of a heterologous-insert prime-boost HIV vaccine regimen that uses inserts from different HIV-1 subtypes and different adenovirus vectors. This study will enroll healthy, HIV-uninfected people. Participants will be randomly assigned to one of five study groups: * Group 1 will receive the recombinant adenovirus serotype 35 (rAd35) Env A vaccine at baseline and the recombinant adenovirus serotype 5 (rAd5) Env A vaccine at Month 3. * Group 2 will receive the rAd35 Env A vaccine at baseline and the rAd5 Env B vaccine at Month 3. * Group 3 will receive the rAd35 Env A vaccine at baseline and at Month 3. * Group 4 will receive the rAd5 Env A vaccine at baseline and at Month 3. * Group 5 will receive the rAd5 Env A vaccine at baseline and the rAd5 Env B vaccine at Month 3. All vaccines will be injected into the upper arm. At both vaccination study visits, participants will undergo a physical exam, a medical and medication history review, a blood and urine collection, and questionnaires. Participants will receive counseling on HIV risk reduction and pregnancy prevention. After receiving the vaccine, participants will remain in the clinic for at least 30 minutes for observation and monitoring of side effects. For 3 days after each vaccination, participants will record their temperature and side effects in a symptom log. In addition to the vaccine study visits, other study visits will occur at Week 2, two weeks after the Month 3 visit, and at Months 4, 6, and 9, at which time various study procedures will be repeated. Participants will be contacted by study researchers once a year for 5 years for follow-up safety monitoring. Safety monitoring will not involve visiting a clinic except if a confirmatory HIV test is needed. Questions will assess health and adverse events. The primary objective of this study is to assess the safety and tolerability, as well as the ability, of a heterologous-insert prime-boost vaccine regimen using env inserts from different HIV-1 clades to increase T-cell responses. In addition, this study is evaluating the effectiveness of a heterologous-insert prime-boost and vector prime-boost vaccine regimen at increasing T-cell responses. The study will also compare the degree of polyfunctionality of insert specific T cells after vaccination within heterologous and homologous vector vaccine regimens.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Assessed by clinic staff as being "low risk" for HIV infection
- •Access to a participating HIV Vaccine Trials Network (HVTN) clinical research site (CRS) and willing to be followed for the duration of the study
- •Able and willing to provide informed consent
- •Assessment of understanding, including the completion of a questionnaire before the first vaccination and demonstration of understanding for all questionnaire items answered incorrectly
- •Willing to receive HIV test results
- •Willing to discuss HIV infection risks, amenable to HIV risk reduction counseling, committed to maintaining behavior consistent with low risk of HIV exposure through the last required study visit
- •Willing to continue annual follow-up contact after the final study visit for a total of 5 years after study entry
- •In good general health, as shown by medical history, physical exam, and screening laboratory tests
- •Assessed by the clinic staff as having a low risk of HIV infection on the basis of sexual behaviors in the 12 months before study entry. More information on this criterion can be found in the protocol.
- •Adenovirus 5 nAb titer less than 1:18
Exclusion Criteria
- •Excessive daily alcohol use, frequent binge drinking, chronic marijuana abuse, or use of any other illicit drugs in the 12 months before study entry
- •History of newly acquired syphilis, gonorrhea, non-gonococcal urethritis, herpes simplex virus type 2 (HSV2), chlamydia, pelvic inflammatory disease (PID), trichomonas, mucopurulent cervicitis, epididymitis, proctitis, lymphogranuloma venereum, chancroid, or hepatitis B in the 12 months before study entry
- •Received non-HIV experimental vaccines in a previous vaccine trial in the 5 years before study entry
- •Received HIV vaccines in a prior HIV vaccine trial
- •Immunosuppressive medications received within 168 days before the first study vaccination
- •Blood products received within 120 days before the first study vaccination
- •Immunoglobulin received within 60 days before the first study vaccination
- •Live attenuated vaccines received within 30 days before the first study vaccination or scheduled within 14 days after injection
- •Investigational research agents received within 30 days before the first study vaccination
- •Intent to participate in another investigational drug study
Outcomes
Primary Outcomes
Frequency of adverse events (AEs) categorized by MedDRA body system, MedDRA preferred term, severity and assessed relationship to study products; detailed description of all AEs meeting DAIDS criteria for expedited reporting
Time Frame: Measured at Month 9
Frequency and severity of local injection site reactogenicity signs and symptoms, including pain, tenderness, erythema, induration, and maximum severity of pain and/or tenderness
Time Frame: Measured at baseline and Month 3
Number of participants with early discontinuation of vaccinations and reason for discontinuation
Time Frame: Measured at Month 9
Distribution of values of safety laboratory measures, including white blood cells (WBCs), neutrophils, lymphocytes, hemoglobin, platelets, and alanine aminotransferase (ALT) at baseline and at postvaccination follow-up study visits
Time Frame: Measured at Month 9
Number of shared HIV epitopes targeted by T-cells
Time Frame: Measured at 4 weeks following the final vaccination
Frequency and severity of systemic reactogenicity signs and symptoms, including fever, malaise/fatigue, myalgia, headache, nausea, vomiting, chills, arthralgia, and maximum severity of systemic symptoms
Time Frame: Measured at baseline and Month 3
HIV-1-specific interferon gamma (IFN-y) ELISpot responses
Time Frame: Measured at 4 weeks following the final vaccination
Secondary Outcomes
- Binding and neutralizing antibody titers(Measured at baseline and at 4 weeks following the final vaccination)
- Number of shared HIV epitopes targeted by T-cells(Measured at 4 weeks following the final vaccination)
- HIV-1-specific IFN-y ELISpot responses(Measured at 4 weeks following the final vaccination)
- Frequency of insert-specific CD4 and CD8 cells(Measured at 4 weeks following the final vaccination)
- Functional spectrum of CD4 and CD8 cells by intracellular cytokine staining (ICS) assay for IFN-y, IL-2, and TNF-a(Measured at Month 9)
- Number of HIV epitopes targeted by T-cells(Measured at 4 weeks following the final vaccination)