A Phase I Study of the Safety and Immunogenicity of PENNVAX-G DNA (ENV & GAG) Administered by Intramuscular Biojector 2000 or CELLECTRA Intramuscular Electroporation Device Followed by MVA-CMDR (HIV-1 CM235 ENV/CM240 GAG/POL) Boost in Healthy, HIV Uninfected Adults
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- HIV Infections
- Sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)
- Enrollment
- 92
- Locations
- 4
- Primary Endpoint
- Severe local toxicity at injection site
- Status
- Completed
- Last Updated
- 4 years ago
Overview
Brief Summary
The purpose of this study is to evaluate the safety of and immune response to an HIV vaccine, administered using two different devices, followed by a vaccine boost, in healthy, HIV-uninfected adults.
Detailed Description
Despite advances in treatment, HIV/AIDS rates remain high in low- and middle-income countries in resource-limited areas of the world. Preventive HIV vaccines would be an effective way to decrease the spread of HIV/AIDS. This study will evaluate an experimental HIV preventive vaccine followed by booster: the PENNVAX-G DNA vaccine and the Modified Vaccinia Ankara-Chiang Mai Double Recombinant (MVA-CMDR) booster vaccine. The MVA virus is a mild form of a vaccinia virus that is used in smallpox vaccines and does not cause smallpox infection. It has been safely used in vaccines for many years. Study researchers will examine if the combination of the two vaccines will provide an effective way for the body to build a defense against HIV. The PENNVAX-G vaccine will be administered to participants using one of two devices-the Biojector 2000 needleless device or the CELLECTRA intramuscular (IM) electroporation (EP) device-to evaluate how the immune response to the vaccine changes based on the device that is used. The purpose of this study is to evaluate the safety and immunogenicity of the PENNVAX-G vaccine, administered by either Biojector 2000 injection or CELLECTRA EP, followed by an MVA-CMDR vaccine boost, in healthy, HIV-uninfected adults. This study will be conducted in two parts. Participants in the first part of the study will attend a baseline study visit, and they will undergo blood and urine collection, a medical history review, physical examination, and HIV testing counseling. All participants will receive the PENNVAX-G vaccine at baseline and Day 28. They will be randomly assigned to receive the vaccine by either the Bioinjector 2000 needleless device or the CELLECTRA IM EP device. On Days 84 and 168, all participants will receive the MVA-CMDR vaccine by IM injection delivered via needle and syringe. Participants will remain in the clinic for 1 hour after each vaccination for observation and vital sign monitoring, and they will record their temperatures and any symptoms in a diary for 7 days after each vaccination. Study staff will contact participants 1 to 2 days after each vaccination for follow-up monitoring. In addition to the vaccination study visits, participants will attend study visits at Weeks 1, 2, 4, 5, 6, 13, 14, 25, 26, 37, 50, and 52 and will repeat the baseline study procedures. At the conclusion of the first part of the study, participants' study data will be reviewed and the safety of the vaccine regimen will be determined. If the regimen is found to be safe, then the second part of the study will begin. Participants in the second part of the study will be randomly assigned to receive the PENNVAX-G vaccine administered by either the Bioinjector 2000 device or the CELLECTRA EP device at baseline and Day 28, followed by the MVA-CDMR boost at Days 84 and 168, or they will receive placebo PENNVAX-G vaccine administered by either the Bioinjector 2000 device or the CELLECTRA EP device at baseline and Day 28, followed by a placebo MVA-CDMR boost at Days 84 and 168. All study visits and procedures that occurred during the first part of the study will also take place in the second part of the study. Participants in the second part of the study will have the option of enrolling in a substudy. The purpose of the substudy is to evaluate the antibody response of the reproductive tract mucosa to the PENNVAX-G DNA, MVA-CDMR, and placebo vaccines administered in the main part of study. The substudy will also evaluate the effectiveness of using the Instead Softcup as a collection method to collect vaginal secretions for testing. Mucosal specimens and urine samples will be collected from participants at the screening visit and during the Week 2, 6, 14, 26, and 50 study visits.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Low risk of HIV infection (as defined by the Study Risk Assessment Tool captured during the medical history)
- •Amenable to HIV risk reduction counseling, committed to maintaining behavior consistent with low risk of HIV exposure through the last required protocol clinic visit, and committed to 18 months of follow-up contact
- •Pass the Test of Understanding and demonstrate an understanding of STEP study results (HVTN 502/Merck 023 trial)
- •Assessed by the clinic staff as being at low risk of HIV infection on the basis of sexual behaviors within the 12 months prior to enrollment as follows: sexually abstinent, or had two or fewer mutually monogamous relationships with HIV-uninfected partners and who have not used illicit drugs, or had two or fewer partners believed to be HIV uninfected and who did not use illicit drugs and with whom he/she regularly uses condoms for sexual intercourse
- •Healthy men and women (determined by medical history, physical examination, and clinical judgment)
- •Available and willing to participate for 12 months for study visits and annual follow-up for 18 months after study completion
- •Must be willing to have photo or fingerprint taken for identification purposes
- •Must be willing to be taken home at enrollment visit and allow home visits, if needed
- •Able to read and willing to complete the informed consent process
- •Has the following laboratory criteria within 45 days prior to study entry:
Exclusion Criteria
- •Confirmed HIV-1 or HIV-2 infection
- •Engaged in excessive daily alcohol use, frequent binge drinking, or illicit drug use within the 12 months prior to study entry
- •History of new onset, sexually acquired infection, as determined by local, syndromic diagnostics standards or, as available, serologic and microbiologic diagnosis within the 12 months prior to study entry
- •Has a known current high-risk partner or had such a partner within the 12 months prior to study entry
- •Hepatitis B, hepatitis C, or syphilis infection; active syphilis documented by exam or serology unless positive serology is because of remote treated infection or positive rapid plasma reagin
- •Pregnant, planning on becoming pregnant during the study, or breastfeeding
- •Any clinically significant acute or chronic medical condition that, in the opinion of the investigator, would preclude study participation (e.g., history of seizure disorders, bleeding/clotting disorder, autoimmune disease, malignancy, tuberculosis, other systemic infections)
- •Major surgery within the 4 weeks prior to study entry
- •History of or known active heart disease including:
- •Previous myocardial infarction (heart attack)
Outcomes
Primary Outcomes
Severe local toxicity at injection site
Time Frame: Measured after each vaccination
Severe systemic symptoms judged to be probably or definitely related to the vaccine
Time Frame: Measured after each vaccination