A Phase 1 Clinical Trial to Evaluate the Safety and Immunogenicity of VSV-Indiana HIV Gag Vaccine Given Intramuscularly in Healthy, HIV-1-Uninfected Adult Participants
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- HIV Infections
- Sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)
- Enrollment
- 60
- Locations
- 4
- Primary Endpoint
- Change in frequency and severity of local injection site 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 HIV-uninfected adults. Study researchers will also determine the maximum dose of the vaccine that participants can safely receive.
Detailed Description
Many HIV vaccines that are in development use a virus vector to deliver the vaccine into the body's cells in order to elicit an immune response. Vesicular stomatitis virus (VSV) is a vector that has been studied in animals. As an HIV vaccine vector, it has been shown to prevent disease progression in monkeys infected with simian/human immunodeficiency virus (SHIV). This study will evaluate the safety and immune response to the VSV-Indiana (one type of VSV vector) HIV gag vaccine in healthy, HIV-uninfected adults. In addition, study researchers will determine the maximum dose of the vaccine that can be safely tolerated. This study will enroll healthy, HIV-uninfected adults. Five groups of participants will be enrolled, with each subsequent group receiving a slightly higher dose of the vaccine. Within each group, participants will be randomly assigned to receive the study vaccine or a placebo vaccine. Study researchers will examine safety data and how participants react to the study vaccine before enrolling the next group of participants. At baseline and Week 8, participants will receive two injections of the study vaccine or placebo vaccine-one in each upper arm at each time point. At the baseline study visit, all participants will undergo a physical examination; mouth examination; a medical and medication history review; and saliva, blood, and urine collection. Female participants will also take a pregnancy test. Participants will complete questionnaires to assess mental status and 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 7 days after the vaccination, participants will record any side effects in a symptom log. Participants will attend study visits 3 days and 1 and 2 weeks after the baseline study visit, at Week 8 for the second vaccination, 3 days and 1 and 2 weeks after the Week 8 visit, and at Months 5 and 8. Follow-up study visits will include select baseline study procedures. Participants will be contacted annually for 3 years 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
- •Demonstrate understanding of this study by completing 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 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 study clinic visit (excludes annual contacts for safety surveillance)
- •In 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, greater than or equal to 13.0 g/dL for participants who were born male
Exclusion Criteria
- •Excessive daily alcohol use, frequent binge drinking, chronic marijuana abuse, or any other use of illicit drugs within the 6 months prior to 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 within the 12 months prior to study entry
- •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 090 Protocol Safety Review Team (PSRT) will determine eligibility on a case-by-case basis.
- •Non-HIV experimental vaccine(s) received within the 5 years prior to study entry 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 090 PSRT will determine eligibility on a case-by-case basis. For potential participants who have received an experimental vaccine(s) greater than 5 years prior to study entry, eligibility for enrollment will be determined by the 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 \[length of therapy 10 days or fewer with completion at least 30 days prior to study entry\].)
- •Blood products received within 120 days before first vaccination
- •Immunoglobulin received within 12 months 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)
- •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)
Outcomes
Primary Outcomes
Change in frequency and severity of local injection site reactogenicity signs and symptoms
Time Frame: Measured at Days 0, 1, 2, 4, 5, 6, 7, 60, 61, 62, 63, 64, 65, 66, and 67
Pain, tenderness, erythema, induration, and maximum severity of pain and/or tenderness; frequency and severity of systemic reactogenicity signs and symptoms: fever, malaise/fatigue, myalgia, headache, nausea, vomiting, chills, arthralgia, and maximum severity of systemic symptoms
Frequency of adverse events (AEs) categorized by Medical Dictionary for Regulatory Activities (MedDRA) body system
Time Frame: Participants will be followed for the duration of the study, an expected average of 8 months
Frequency of AEs categorized by MedDRA body system, MedDRA preferred term, severity and assessed relationship to study products; detailed description of all serious adverse events (SAEs)
Change in distribution of values of safety laboratory measures
Time Frame: Measured at Days 3, 5, 9, and 140
White blood cells (WBCs), neutrophils, lymphocytes, hemoglobin, alkaline phosphatase, platelets, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and creatinine at baseline and at follow-up visits postvaccination
Number of participants with early discontinuation
Time Frame: Participants will be followed for the duration of the study, an expected average of 8 months
Number of participants with early discontinuation of vaccinations and reason for discontinuation
Secondary Outcomes
- Change in response rates of CD4 T-cell responses(Measured at Days 7, 14, 68, and 70)
- Change in response rates of CD8 T-cell responses(Measured at Days 7, 14, 68, and 70)
- Change in response rates of T-cell responses(Measured at Days 7, 14, 68, and 70)
- Change in induction of binding antibodies to HIV-1 gag(Measured at Days 7, 14, and 70)