HIV Infections
Conditions
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.
Interventions
BIOLOGICALGEO-D03 DNA vaccine
Either a 0.3-mg (Group 1: study vaccine) or 3-mg dose (Groups 2 and 3: study vaccine) administered as a 1-mL IM injection into the deltoid
BIOLOGICALMVA/HIV62B (MVA62B) vaccine
1 x 10\^8-TCID50 dose of MVA62B vaccine, administered as a 1-mL IM injection into the deltoid
BIOLOGICALPlacebo for GEO-D03 DNA
Administered as a 1-mL IM injection into the deltoid
BIOLOGICALPlacebo for MVA62B:
Administered as a 1-mL IM injection into the deltoid
Sponsors
GeoVax, Inc.
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
Yes
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 * White blood cell (WBC) count of 3,300 to 12,000 cells/mm\^3 * Total lymphocyte count greater than or equal to 800 cells/mm\^3 * Remaining differential either within institutional normal range or with site physician approval * Platelet level of 125,000 to 550,000/mm\^3 * Chemistry panel: ALT, AST, alkaline phosphatase, and creatinine values less than or equal to institutional upper limits of normal * Negative HIV-1 and HIV-2 blood test: U.S. participants must have a negative Food and Drug Administration (FDA)-approved immunoassay * Negative hepatitis B surface antigen (HBsAg) * Negative anti-hepatitis C virus (HCV) antibodies or negative HCV polymerase chain reaction (PCR) if the anti-HCV is positive * Normal urine: negative urine glucose, negative or trace urine protein, and negative or trace urine hemoglobin (if trace hemoglobin is present on dipstick, a microscopic urinalysis for red blood cells \[RBCs\] within institutional normal range) * Participants who were born female: negative serum or urine beta human chorionic gonadotropin (HCG) pregnancy test performed prior to vaccination on the day of initial vaccination * Reproductive status: A participant who was born female must either: (1) Agree to consistently use effective contraception for sexual activity that could lead to pregnancy, from at least 21 days prior to enrollment through the last required protocol clinic visit. Effective contraception is defined as using any of the following methods: condoms (male or female) with or without a spermicide, diaphragm or cervical cap with spermicide, intrauterine device (IUD), hormonal contraception, or successful vasectomy in the male partner (considered successful if a participant reports that a male partner has either documentation of azoospermia by microscopy or a vasectomy more than 2 years ago with no resultant pregnancy despite sexual activity postvasectomy); or (2) Not be of reproductive potential, such as having reached menopause (no menses for 1 year) or having undergone hysterectomy, bilateral oophorectomy, or tubal ligation; or (3) Be sexually abstinent. * Participants who were born female must also agree not to seek pregnancy through alternative methods, such as artificial insemination or in vitro fertilization until after the last required protocol clinic visit
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 * Influenza vaccine or any vaccines that are not live attenuated vaccines and were received within 14 days prior to first vaccination (e.g., tetanus, pneumococcal, hepatitis A or B) * Allergy treatment with antigen injections within 30 days before first vaccination or that are scheduled within 14 days after first vaccination * Current anti-tuberculosis (TB) prophylaxis or therapy * Clinically significant medical condition, physical examination findings, clinically significant abnormal laboratory results, or past medical history with clinically significant implications for current health. A clinically significant condition or process includes but is not limited to: * A process that would affect the immune response * A process that would require medication that affects the immune response * Any contraindication to repeated injections or blood draws * A condition that requires active medical intervention or monitoring to avert grave danger to the participant's health or well-being during the study period * A condition or process for which signs or symptoms could be confused with reactions to vaccine; or * Any condition specifically listed among the
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Frequency and severity of local injection site reactogenicity signs and symptoms | 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 | 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 | 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 | 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 | Group 1: Measured through Day 425; Group 2: Measured through Day 667; Group 3: Measured through Day 607 | — |
Secondary
| Measure | Time frame |
|---|---|
| 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 |
| 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 |
| 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 |
| Concentrations of cytokines and chemokines in serum and/or plasma samples | Measured through Day 126 (in Groups 2 and 3) |
| Blood concentrations of lymphocyte populations (T, B, and NK cells), dendritic cells, monocytes, and granulocytes | Measured through Day 126 (in Groups 2 and 3) |
| 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 |
| 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 |
Countries
United States
Outcome results
None listed