A Phase 1 Placebo Controlled Clinical Trial to Evaluate the Safety and Immunogenicity of a Prime-Boost Vaccine Regimen of GEO-D03 DNA and MVA/HIV62B Vaccines in Healthy, HIV-1-Uninfected Vaccinia Naive Adult Participants
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- HIV Infections
- Sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)
- Enrollment
- 48
- Locations
- 4
- Primary Endpoint
- Frequency and severity of local injection site reactogenicity signs and symptoms
- Status
- Completed
- Last Updated
- 4 years ago
Overview
Brief Summary
This study will test the safety and immune responses of a prime-boost regimen of two HIV vaccines- a DNA vaccine followed by a modified vaccinia Ankara (MVA) vaccine- in healthy, HIV-uninfected, vaccinia-naive adults.
Detailed Description
Although multiple candidate HIV vaccines are being studied, there is not yet an effective preventive HIV vaccine. This study will test the safety and immune responses of prime-boost regimens of two HIV vaccines: two injections of GEO-D03 DNA priming vaccine followed by either two or three boosting injections of MVA/HIV62B (MVA62B) vaccine. This study will enroll 48 healthy, HIV-1-uninfected, vaccinia-naive adults into 1 of 3 groups. Participants within each group will be randomly assigned to receive either the study vaccine regimen (40 total participants) or placebo vaccine regimen (8 total participants). The total study duration will be approximately 45 months. Participants in Group 1 will attend clinic visits for 14 months followed by annual health contacts, for a total of 3 years after initial study injection. Participants in Group 2 will attend clinic visits for 22 months followed by annual health contacts, for a total of 3 years after initial study injection. Participants in Group 3 will attend clinic visits for 20 months followed by annual health contacts, for a total of 3 years after initial study injection. Participants in Group 1 will have 17 study visits, participants in Group 2 will have 23 visits, and participants in Group 3 will have 21 visits. At the screening visit, participants will give a medical history and undergo a complete physical exam, electrocardiogram (ECG), urine collection, blood collection, interview, HIV test, and pregnancy test (for participants who were born female). Participants will receive an intramuscular (IM) vaccination (study vaccine or placebo) into the deltoid on the schedule assigned to their group. The vaccination schedule is as follows: Group 1 participants will receive an injection on Days 0, 56, 112, 168, and 224; Group 2 participants will receive an injection on Days 0, 56, 112, 168, and 303; Group 3 participants will receive an injection on Days 0, 56, 112, and 224. On vaccination visits, participants will also undergo an abbreviated physical exam, a pregnancy test (for participants who were born female), risk-reduction counseling, and blood collection. Immediately following vaccination, participants will remain in the clinic for observation for 30 minutes; participants will be given a post-vaccination symptom log and instructed on how to complete it. Follow-up visits will consist of a brief physical exam, blood collection, and interview; some follow-up visits may also consist of a urine collection, HIV test, or ECG. The last clinic visit will be at Day 425 for participants in Group 1, Day 667 for participants in Group 2, and Day 607 for participants in Group 3; after this visit, participants will be contacted for annual health follow-up consisting of confirming vital status, collecting safety information, and reporting a new HIV diagnosis or a pregnancy. A clinic visit will only be required if HIV confirmatory testing is necessary.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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: participant demonstrates understanding of this study and completes a questionnaire prior to first vaccination with verbal demonstration of understanding of all questionnaire items answered incorrectly
- •Willingness to receive HIV test results
- •Willingness 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 protocol clinic visit
- •Willing to be contacted annually after completion of scheduled clinic visits for a total of 3 years following initial study injection
- •Agrees not to enroll in another study of an investigational research agent prior to completion of last required protocol clinic visit (excludes annual contacts for safety surveillance)
- •Good general health as shown by medical history, physical exam, and screening laboratory tests
- •Assessed by the clinic staff as being at low risk of HIV infection
- •Hemoglobin greater than or equal to 11.0 g/dL for participants who were born female, or greater than or equal to 13.0 g/dL for participants who were born male
Exclusion Criteria
- •Vaccinia (smallpox) vaccine determined by (1) clinical evidence of vaccinia scarification; (2) self-reported history of vaccinia vaccination; (3) date of birth; or (4) U.S. military service prior to 1989 or after December 2002 (not excluded: a participant born before 1975, or with past U.S. military service, who self-reports he/she did not receive vaccinia vaccine and has no evidence of scarification)
- •Untreated or incompletely treated syphilis infection
- •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 094 Protocol Safety Review Team (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 for vaccines that have subsequently undergone licensure by the FDA. For potential participants who have received control/placebo in an experimental vaccine trial, the HVTN 094 PSRT will determine eligibility on a case-by-case basis. For potential participants who have received an experimental vaccine(s) greater than 5 years ago, eligibility for enrollment will be determined by the HVTN 094 PSRT on a case-by-case basis.
- •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 enrollment)
- •Blood products received within 120 days before first vaccination
- •Immunoglobulin received within 60 days before first vaccination
- •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)
- •Investigational research agents received within 30 days before first vaccination
- •Intent to participate in another study of an investigational research agent during the planned duration of the HVTN 094 study
Outcomes
Primary Outcomes
Frequency and severity of local injection site reactogenicity signs and symptoms
Time Frame: Measured within the initial 72-hour period following each vaccination visit (Days 0, 56, 112, 168, 224, and 303)
Signs and symptoms include pain, tenderness, erythema, induration, and maximum severity of pain and/or tenderness.
Frequency and severity of systemic reactogenicity signs and symptoms and maximum severity of systemic symptoms
Time Frame: Measured within the initial 72-hour period following each vaccination visit (Days 0, 56, 112, 168, 224, and 303)
Systemic reactogenicity signs and symptoms include fever, malaise/fatigue, myalgia, headache, nausea, vomiting, chills, and arthralgia.
Distribution of values of safety laboratory measures: complete blood count (CBC), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, and creatinine
Time Frame: Group 1: Measured through Day 334; Group 2: Measured through Day 394; Group 3: Measured through Day 334
Frequency of adverse events (AEs) categorized by MedDRA System Organ Class and MedDRA Preferred Term; severity and assessed relationship to study products; detailed description of all AEs meeting DAIDS criteria for expedited reporting
Time Frame: Group 1: Measured through Day 425; Group 2: Measured through Day 667; Group 3: Measured through Day 607
Report of the number of participants with early discontinuation of vaccinations, by treatment group and reason for discontinuation
Time Frame: Group 1: Measured through Day 425; Group 2: Measured through Day 667; Group 3: Measured through Day 607
Secondary Outcomes
- Frequency and magnitude of HIV-1 envelope (env)-specific binding antibody and isotypes(Group 2: Measured at Day 317; Group 3: Measured at Day 238)
- Frequency of neutralizing antibody responses to HIV-1(Group 2: Measured at Day 317; Group 3: Measured at Day 238)
- In individuals with neutralizing antibodies to HIV-1, neutralizing antibody titers (magnitude) and breadth of neutralizing activity(Group 2: Measured at Day 317; Group 3: Measured at Day 238)
- Frequency and magnitude of HIV-1 specific CD4+ and CD8+ T cell responses as measured by intracellular cytokine staining (ICS) at 2 weeks after the second vaccination for Groups 2 and 3(Measured at Day 70)
- Frequency and magnitude of HIV-1 specific CD4+ and CD8+ T cell responses as measured by ICS at 2 weeks after the last vaccination for Groups 2 and 3(Group 2: Measured at Day 317; Group 3: Measured at Day 238)
- Avidity indices for env-specific binding antibody(Group 2: Measured at Day 317; Group 3: Measured at Day 238)
- Concentrations of secreted cytokines and chemokines by multiplex analysis of stimulated cell supernatants following peptide stimulation of PBMC 2 weeks after the last vaccination for Groups 2 and 3(Group 2: Measured at Day 317; Group 3: Measured at Day 238)
- Blood concentrations of lymphocyte populations (T, B, and NK cells), dendritic cells, monocytes, and granulocytes(Measured through Day 126 (in Groups 2 and 3))
- Concentrations of cytokines and chemokines in serum and/or plasma samples(Measured through Day 126 (in Groups 2 and 3))