Study of Safety and Immunogenicity of HIV Vaccines in Healthy Volunteers
Condition: Vaccine Response
Study type: Interventional
Phase: Phase 1

Summary: 
      Background:

      - Vaccines create resistance to disease. This study tests experimental human immunodeficiency
      virus (HIV) vaccines that use an adenovirus as a transporter. Transporters may help vaccines
      stimulate an immune response against HIV. This means the body works to fight infection.
      Researchers want to see if different ways of giving the vaccines cause different immune
      responses. They also want to see if the vaccines adenovirus is contagious. Adenoviruses cause
      cold symptoms or mild eye infections.

      Participants cannot get HIV from these vaccines. But they can get the adenovirus, so their
      entire household and intimate contacts must participate.

      Objective:

      - To test the safety of experimental HIV vaccines.

      Eligibility:

      - Healthy adults 18-49 years old.

      Design:

        -  Participants will be screened with medical history, physical exam, and blood and urine
           tests.

        -  Participants will receive the vaccine 3 times over 6 months. Each time, they will have a
           physical exam and blood and urine tests. Samples will be taken from their nose, rectum,
           and cervix.

        -  Some participants will receive the vaccine by swallowing 11 capsules with water. Clinic
           staff will observe them for 1 hour.

        -  Some participants will receive the vaccine swabbed in their throat. They will get dose 1
           at the hospital and stay there for 1 week. They will have medical tests and nose swabs.
           Doses 2 and 3 will not require a hospital stay.

        -  Participants will have 7 follow-up visits over 6 months, with a physical exam and blood
           tests. Samples will be taken from their nose, throat, and rectum.

        -  Household and intimate contacts will have 4 clinic visits over 8 months, with a physical
           exam and blood tests.
    

Detailed description: 
      This is a Phase 1, single center, randomized, double-blind study designed to evaluate the
      safety and immunogenicity of live, replication-competent recombinant Adenovirus type 4-HIV
      vaccine regimens. The oral route will also contain a placebo control. The vaccine candidates
      Ad4-mgag and Ad4-EnvC150 will be formulated as enteric-coated capsules to be delivered
      orally, and as an aqueous formulation for intranasal administration. Determining the optimal
      regimen and route will greatly accelerate investigations of these vectors as HIV vaccine
      platforms.

      Participants volunteering to receive the vaccine orally will be randomized to 1 of 4
      treatment arms, and those volunteering to receive the vaccine via the intranasal route will
      be randomized to 1 of 3 treatment arms. Participants will receive either 1 or both vaccines
      or placebo, depending on group assignment. The study vaccines will be administered to
      participants in 3 rounds of vaccination at 0, 2, and 6 months. All participants will receive
      a booster vaccination with a bivalent HIV gp120 glycoprotein at 8 months. Intranasal vaccine
      recipients with household contact(s) will receive the first vaccine in the NIH Special
      Clinical Studies Unit or other appropriate unit and be followed on an inpatient basis to
      allow for respiratory isolation. Intranasal vaccinees without household contact(s) may also
      receive the vaccination as inpatients or may opt to receive the vaccine on an outpatient
      basis if they agree to follow precautions for preventing the spread of adenovirus. Beginning
      4 days after vaccination, inpatient participants will be tested daily for respiratory
      shedding of Ad4 by nasopharyngeal wash. They will be discharged to home with close monitoring
      on Day 7 or after 2 consecutive negative washes, whichever comes first; they may remain on
      the unit longer if medically necessary. Prior to receiving the second dose of vaccine on an
      outpatient basis, seroconversion to Ad4 will be confirmed in the intranasal vaccine
      recipients. Those who have household contact(s) and have not seroconverted will continue to
      receive subsequent doses as inpatients until they show seroconversion. Those who do not have
      household contact(s) and those who have seroconverted may receive the remaining vaccinations
      as inpatients or may opt to receive the doses on an outpatient basis if they agree to follow
      precautions for preventing the spread of adenovirus. If they decline these options, they may
      withdraw from the study and will be replaced. Oral capsule recipients will be vaccinated and
      discharged to home.

      In addition to clinical and laboratory monitoring of safety, the principal assessments will
      be shedding of this viruses in rectal, cervicovaginal, throat, and nasal swabs, and
      assessment of the antibody (mucosal and systemic) response to the HIV and to the Ad4 virus.

      The candidate vaccines will also be administered to 2 groups of participants who have
      previously received an unrelated HIV vaccine in another clinical study and/or are Ad4
      seropositive. The aim for these groups is to explore the boost potential of the enteric
      coated capsule and aqueous formulations of the Ad4-mgag and Ad4- EnvC150 vaccines when given
      to subjects who have previously received another HIV vaccine and/or are Ad4 seropositive.

      The adenovirus vaccines will not be retested for stability in 2018, and therefore will be out
      of specifications on May 9th 2018. In an effort to capture as much information on
      immunogenicity and adenoviral replication as possible, we will implemement the following
      change beginning in 2018. The study will continue with enrollment into the remaining
      treatment groups in a nonrandomized manner such that remaining participants receive both the
      Ad4-mgag and Ad4-EnvC150 intranasally. These participants will receive 2 rounds of the
      intranasal vaccine at Months 0 and 2 followed by a single dose of the booster vaccination at
      Month 4.

      All participants will be followed for a total of 6 months following the final dose of study
      vaccine. Household and intimate contacts will also be enrolled and monitored for Adenovirus
      and HIV antibodies for up to 8 months.
    

Intervention name(s): Ad4-mgag; Ad4-EnvC150; gp 120 Protein Boost
Intervention type(s): Biological; Biological; Biological
Intervention description(s): Ad4 live virus vaccine with an HIV insert; Ad4 live virus vaccine with an HIV insert; HIV protein boost
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Prevention
Keywords: HIV Vaccine; Healthy Volunteer