A Phase I Open-Label Trial to Evaluate the Safety and Immunogenicity of an HIV-1 Subtype C gp140 Vaccine With MF59 Adjuvant in Healthy, HIV-1 Uninfected Adult Participants Previously Primed or Unprimed With HIV-1 Subtype B Envelope Subunit Vaccines With MF59
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- HIV Infections
- Sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)
- Enrollment
- 36
- Locations
- 3
- Primary Endpoint
- Frequency of severe local and systemic reactogenicity signs and symptoms
- Status
- Completed
- Last Updated
- 4 years ago
Overview
Brief Summary
The purpose of this study is to evaluate the safety and immune response to an HIV vaccine in healthy, HIV-uninfected adults who have participated in a previous HIV vaccine clinical trial and in healthy, HIV-uninfected adults who have not participated in a previous HIV vaccine clinical trial.
Detailed Description
Previous clinical trials have shown that people who receive a second vaccine for certain conditions after having received a prior vaccine may have a better antibody response to the second vaccine than people who receive the vaccine for the first time. This is known as "priming" and it may occur in people receiving a second vaccine even if the first vaccine was received several years previously. This study will enroll healthy, HIV-uninfected adults who have participated in a previous HIV vaccine clinical trial and received HIV-1 subtype B envelope subunit vaccines with MF59 adjuvant, and healthy, HIV-uninfected adults who have not participated in a previous HIV vaccine clinical trial and therefore have not previously received any HIV vaccines. Participants in this study will receive a total of two injections, each 6 months apart, of the HIV-1 Sub Cgp140 vaccine with MF59 adjuvant. Researchers will evaluate the safety and immune response to the study vaccine and determine if people who participated in a previous HIV vaccine clinical trial demonstrate an improved antibody response to the study vaccine versus people who have never received an HIV vaccine. This study will enroll two groups of participants. Group 1 will include healthy, HIV-uninfected adults who have participated in a previous HIV vaccine clinical trial. Group 2 will include healthy, HIV-uninfected adults who have not participated in an HIV vaccine clinical trial. All participants will receive the study vaccine injected into their upper arm at baseline and Month 6. At the baseline study visit, all participants will undergo a physical examination, a medical and medication history review, and blood collection. Female participants will also take a pregnancy test. Participants will complete questionnaires and receive counseling on HIV risk reduction and pregnancy prevention. Saliva samples will be obtained from all participants and rectal fluids, semen samples, and cervical secretions will be obtained from some participants. 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 the vaccination, participants will record any side effects in a symptom log. Participants in Group 1 will attend study visits 1 and 2 weeks after the first vaccination study visit, at Month 6 for the second vaccination, 1 and 2 weeks after the Month 6 study visit, and at Months 9 and 12. Participants in Group 2 will attend study visits 1 and 3 days and 1 and 2 weeks after the first vaccination study visit, at Month 6 for the second vaccination, 1 and 3 days and 1 and 2 weeks after the Month 6 study visit, and at Months 9 and 12. Follow-up study visits will include select study procedures. Blood collected during study visits may be saved for future testing. Study researchers will contact participants at Month 18 for follow-up health monitoring. In July 2013, an extension to the study was announced. Current study participants will be screened to see if they are eligible to participate in the study extension. Participants who are eligible will receive one additional injection of the study vaccine, at a visit approximately 14 to 20 months after their second (Month 6) vaccination. Additional study visits will occur 2 weeks, and 3 and 6 months after receiving the third vaccination. Select visits will include a physical examination, blood collection, saliva collection, pregnancy test for female participants, HIV testing and risk reduction counseling, and interviews and questionnaires. Study researchers will contact participants 1 year after the third vaccination for follow-up health monitoring.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Access to a participating HVTN Clinical Research Site (CRS) and willing to be followed for the planned duration of the study
- •Able and willing to provide informed consent
- •Assessment of understanding: must demonstrate understanding of this study and the Step Study results; completes a questionnaire prior to first vaccination with verbal demonstration of understanding of all questionnaire items answered incorrectly
- •Willing to receive HIV test results
- •Willing to discuss HIV infection risks, amenable to HIV risk reduction counseling, and committed to maintaining behavior consistent with low risk of HIV exposure through the last required study clinic visit
- •Assessed by the clinic staff as being at low risk for HIV infection
- •Agrees not to enroll in another study of an investigational research agent prior to completion of last required study clinic visit
- •In good general health as shown by medical history, physical exam, and screening laboratory tests
- •For Group 1: Prior receipt of an HIV-1 subtype B envelope subunit vaccine (gp120, gp140) with MF59 adjuvant. More information on this criterion can be found in the protocol.
- •Hemoglobin greater than or equal to 11.0 g/dL for participants who were born female, greater than or equal to 13.0 g/dL for participants who were born male
Exclusion Criteria
- •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 within the 12 months prior to study entry
- •Untreated or incompletely treated syphilis infection
- •For Group 2 only: HIV vaccine(s) received in a prior HIV vaccine trial. For potential participants who have received control/placebo in an HIV vaccine trial, the HVTN 088 Protocol Safety Review Team (PSRT) will determine eligibility on a case-by-case basis.
- •Non-HIV experimental vaccine(s) or adjuvant(s) other than MF59 received within the 5 years prior to study entry in a prior vaccine trial. Exceptions may be made for vaccines/adjuvants that have subsequently undergone licensure by the FDA. For potential participants who have received an experimental vaccine(s)/adjuvant(s) greater than 5 years before study entry, eligibility for enrollment will be determined by the PSRT on a case-by-case basis. For potential participants who have received control/placebo in an experimental vaccine trial, the HVTN 088 PSRT will determine eligibility on a case-by-case basis.
- •Live attenuated vaccines other than influenza vaccine received within 30 days before first vaccination or scheduled within 14 days after injection (e.g., measles, mumps, and rubella \[MMR\]; oral polio vaccine \[OPV\]; varicella; yellow fever)
- •Influenza vaccine or any vaccines that are not live attenuated vaccines (e.g., pneumococcal, tetanus, hepatitis A or B) and were received within 14 days prior to any vaccination
- •Allergy treatment with antigen injections within 30 days before first vaccination or that are scheduled within 14 days after first vaccination
- •Immunosuppressive medications received within 168 days before first vaccination. (Not excluded: \[1\] corticosteroid nasal spray for allergic rhinitis; \[2\] topical corticosteroids for mild, uncomplicated dermatitis; or \[3\] oral/parenteral corticosteroids given for non-chronic conditions not expected to recur \[length of therapy 10 days or less with completion at least 30 days prior to study entry\].)
- •Blood products received within 120 days before first vaccination
- •Immunoglobulin received within 60 days before first vaccination
Outcomes
Primary Outcomes
Frequency of severe local and systemic reactogenicity signs and symptoms
Time Frame: Measured within the first 3 days after vaccination
Summary reports of the frequency of adverse events (AEs) by group, by body system, MedDRA preferred term, severity, and assessed relationship to study product
Time Frame: Measured through 12 months post last vaccination
All serious adverse events (SAEs)
Time Frame: Measured through 12 months post last vaccination
Laboratory measures of safety at baseline and following vaccinations: descriptive analyses of white blood cells (WBC), neutrophils, lymphocytes, hemoglobin, platelets, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and creatinine
Time Frame: Measured through 3 months post last vaccination
Neutralizing antibody titers to SF162 and TV1
Time Frame: Measured through 6 months post last vaccination
Neutralizing antibody titers and breadth against heterologous primary isolates
Time Frame: Measured through 6 months post last vaccination
Secondary Outcomes
- SF162 Env-specific non-neutralizing antibodies and TV1 Env-specific antibodies as determined by multiplex antibody assays(Measured through 6 months post last vaccination)
- ConS gp140 specific IgG subclass characterization (IgG1- IgG4) and IgA measurement by custom HIV-1 multiplex assay(Measured through 6 months post last vaccination)
- Intracellular cytokine staining to evaluate polyfunctional cytokine responses by antigen-specific CD4 T cells(Measured through 6 months post last vaccination)
- Lymphoproliferation of antigen-specific CD4 T cells by carboxyfluorescein diacetate succinimidyl ester (CFSE) assay(Measured through 6 months post last vaccination)