A Phase 1 Randomized, Double-Blind, Placebo Controlled Clinical Trial to Evaluate the Safety, Mucosal Immunogenicity and Innate Immune Responses of Recombinant Adenovirus Serotype 26 HIV-1 Vaccine (Ad26.ENVA.01) in Healthy, HIV-1 Uninfected Adults (Ad26.ENVA.01 (rAd26) HIV-1 Mucosal/IPCAVD-003 Vaccine Study)
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- HIV Infections
- Sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)
- Enrollment
- 24
- Locations
- 1
- Primary Endpoint
- Adverse and serious adverse experiences
- Status
- Completed
- Last Updated
- 8 years ago
Overview
Brief Summary
The purpose of this study is to evaluate the safety and immune response of an adenovirus-based HIV vaccine in HIV-uninfected adults.
Detailed Description
Control of the global HIV pandemic will require the development of a safe and effective vaccine. Many HIV preventive vaccines that are in development use a recombinant adenovirus serotype 5 (rAd5) vector as a way of delivering the vaccine into cells. However, the majority of people, particularly in the developing world, have immunity against the Ad5 vector, which means the vaccine will not be effective at preventing HIV infection. This study will use a rAd26 vector as part of a HIV vaccine, as research has shown that relatively few people have immunity against this vector. The purpose of this study is to evaluate the safety and immunogenicity of a rAd26 vector preventive HIV-1 vaccine. This study will enroll healthy, HIV-uninfected people. Participants will be randomly assigned to receive either the rAd26 vaccine or a placebo vaccine. All vaccines will be injected into the upper arm. At the vaccination study visit, participants will undergo a medical and medication history review, physical examination, and a rectal sampling procedure. They will then receive their assigned vaccine. After receiving the vaccine, participants will remain in the clinic for at least 30 minutes for observation and monitoring of side effects. Participants will receive counseling on HIV risk reduction and pregnancy prevention. For 7 days after the vaccination, participants will monitor their temperature and side effects. Additional study visits will occur at Days 1, 3, 7, 14, 28, 61, 168, and 365. At these visits, participants will undergo a medical history review, physical examination, counseling, and blood collection. At the Day 14 and 168 visits, a rectal sampling procedure will be performed. Participants will attend a study visit or be contacted by study researchers by telephone or e-mail 18 months after receiving the vaccine for follow-up health and safety monitoring. Participants may elect to attend optional follow-up visits for blood collection at Years 2, 3, 4, and 5.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Willing to be followed for the planned duration of the study
- •Able and willing to provide informed consent
- •Assessment of understanding, including the completion of a questionnaire prior to vaccination; verbally demonstrated understanding of all questionnaire items answered incorrectly
- •Willing to receive HIV test results
- •In good general health as shown by medical history, physical exam, and screening laboratory tests
- •Hemoglobin levels greater than or equal to 11.0 g/dL for women and greater than or equal to 12.5 g/dL for men
- •White blood cell (WBC) count between 3,300 and 12,000 cells/mm3
- •Total lymphocyte count greater than or equal to 800 cells/mm3
- •Remaining differential either within institutional normal range or accompanied by site physician approval
- •Platelet levels between 125,000 and 550,000/mm3
Exclusion Criteria
- •Received HIV vaccine(s) in a prior HIV vaccine trial. Participants who received a control/placebo in an HIV vaccine trial are not excluded but documentation of the identity of the study control/placebo must be obtained.
- •Immunosuppressive medications received within 168 days before vaccination (e.g., oral/parenteral corticosteroids, and/or cytotoxic medications). People taking corticosteroid nasal spray for allergic rhinitis and topical corticosteroids for mild, uncomplicated dermatitis are not excluded.
- •Blood products received within 120 days before vaccination
- •Immunoglobulin received within 60 days before vaccination
- •Live attenuated vaccines received within 30 days before vaccination (e.g., measles, mumps, and rubella \[MMR\]; oral polio vaccine \[OPV\]; varicella; yellow fever; Flumist® influenza)
- •Investigational research agents received within 30 days before vaccination
- •Any vaccines that are not live attenuated vaccines and were received within 14 days prior to vaccination (e.g., influenza, tetanus, pneumococcal, Hepatitis A or B)
- •Clinically significant medical condition, physical examination findings, clinically significant abnormal laboratory results, or past medical history with clinically significant implications for current health. More information on this criterion can be found in the protocol.
- •Any medical, psychiatric, or social condition, or occupational or other responsibility that, in the judgment of the investigator, would interfere with, or serve as a contraindication to, protocol adherence, assessment of safety or reactogenicity, or a participant's ability to give informed consent
- •Serious adverse reactions to vaccines including anaphylaxis and related symptoms such as hives, respiratory difficulty, angioedema, and/or abdominal pain. People who had a nonanaphylactic adverse reaction to the pertussis vaccine as a child are not excluded.
Outcomes
Primary Outcomes
Adverse and serious adverse experiences
Time Frame: Measured through the 18-month follow-up visit
Local and systemic reactions to vaccine
Time Frame: Measured through the 18-month follow-up visit
Secondary Outcomes
- Mucosal immune responses, including histopathology and T-cell responses by flow cytometry(Measured through the 18-month follow-up visit)
- Innate immune responses, including cytokine levels and natural killer (NK) cell populations(Measured through the 18-month follow-up visit)
- Humoral immune responses, including neutralizing antibodies against HIV and Ad26 and binding antibodies(Measured through the 18-month follow-up visit)
- Cell mediated immunity, including T-cell gamma interferon responses by enzyme-linked immunosorbent spot (ELISPOT) and T-cell responses by flow cytometry(Measured through the 18-month follow-up visit)
- Genotyping(Measured through the 18-month follow-up visit)