A Prophylactic HIV Vaccine Trial to Evaluate the Safety and Immunogenicity of HIV Clade C DREP Alone and in Combination With a Clade C ENV Protein in Healthy HIV-uninfected Adults

EHVA P01 is an international, phase I, prophylactic HIV vaccine trial to evaluate the safety and immunogenicity of HIV Clade C DREP alone and in Combination with a Clade C ENV protein in healthy HIV-uninfected adults.

The study is looking at the use of a new vaccine against the HIV virus. There are two parts to the study. One part is open-label to assess the safety of this vaccine, since this will be the first time that it has been used in humans. The second part is to see how well, and for how long, the vaccine activates the immune system. But this trial is not looking at whether or not the vaccine is effective in terms of protection against HIV. It is just assessing whether and how well the immune system responds.

Since this is the first time the vaccine has been used in humans, the safety will be assessed initially in healthy young adults. 10 participants aged 18-55 years will be given one of two different doses (0.2 and 1.0 mg) by injection into the arm muscle. There will be careful monitoring for any reactions to the vaccine.

As long as there are no safety concerns, the second part of the study can then be started. This will see how well the immune system has been activated using different dose levels of the vaccine. About 60 participants aged 18-55 years will be given one of three doses schedules (0.2mg, 1.0mg of the new vaccine and 4.0mg of a conventional vaccine). Chance will determine which dose each individual is given. Participants are only blind to the dose of vaccine administered but laboratory technicians assessing the safety parameters and immune responses will be blinded. The vaccine is given by injection into the muscle of the upper arm. Two injections, four weeks apart, are needed for the first part of the trial. There are three vaccinations in part two of the trial. There are likely to be mild side-effects near to the injection site. There may also be more general side-effects such as headache, temperature and chills. Participants will be asked to record any symptoms in an online diary. In order to see how well the immune system is responding, participants will need to give blood samples at several time points. The vaccines are not made from HIV and cannot cause HIV infection. However, the vaccines are likely to cause participants to produce antibodies against HIV that are detected by the rapid HIV antibody tests that are used in routine testing and a test that detects and measures antibodies in the blood used for confirmation. It is recommended that participants have an up to date vaccination status for any required immunisations including authorised COVID-19 vaccines. Vaccination with licensed (including authorised COVID-19) vaccines should be avoided from 28 days before and after each injection .

An independent steering committee will regularly review the information on safety and look at the immune responses to see which dose of the candidate vaccine could go forward to effectiveness testing in future trials. Before this study can start, the protocol describing the procedures and information to be provided to volunteers will be reviewed by the national drug authority and a multi-centre research ethics committee in the participating countries.

Eligibility Criteria:
Inclusion Criteria:

1. Healthy adults aged 18- 55 years on the day of screening
2. BMI between 18-30 kg/m2 (inclusive)
3. Unlikely to acquire HIV during follow-up
4. Willing and able to provide written informed consent
5. If female and of childbearing potential\* age and not sterilised, willing to use a highly effective method of contraception from screening until 12 weeks after last injection
6. If male and not sterilised, willing to avoid impregnating female partners from screening until 12 weeks after last injection\*\*
7. Willing to avoid all other vaccines from 28 days before the first injection through to 28 days after subsequent study injections
8. Willing and able to comply with visit schedule and provide blood samples
9. Being covered by medical insurance or in National Healthcare System

   * A woman will be considered of childbearing potential following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy.

     * It is recommended that participants have an up to date vaccination status for any required immunisations including authorised COVID-19 vaccines

Exclusion Criteria:

1. Pregnant or lactating
2. Has a significant clinical history, physical finding on clinical examination during screening, or presence of a disease that is active or requires treatment to control it, including cardiac, respiratory, endocrine, metabolic, autoimmune, liver, neurological, oncological, psychiatric, immunosuppresive/immunodeficient or other disorders which in the opinion of the investigator is not compatible with healthy status, may compromise the volunteer's safety, preclude vaccination or compromise interpretation of the immune response to vaccine. Individuals with mild/moderate, well-controlled comorbidities are allowed.
3. HIV 1 or 2 infection or indeterminate test at screening
4. History of anaphylaxis or angioedema
5. History of severe or multiple allergies to drugs or pharmaceutical agents
6. Known hypersensitivity to any component of the vaccine formulation used in this trial
7. History of severe local or general reaction to vaccination defined as

   1. local: extensive, indurated redness and swelling involving most of the arm, not resolving within 72 hours
   2. general: fever \>= 39.5oC within 48 hours; anaphylaxis; bronchospasm; laryngeal oedema; collapse; convulsions or encephalopathy within 72 hours
8. Receipt of any experimental vaccine within 5 years from screening.
9. Receipt of blood products or immunoglobulins within 18 weeks of screening.
10. Receipt any of immunosuppressive agents within 18 weeks of screening by any route other than skin and intranasal.
11. Detection of antibodies to hepatitis B \& C
12. Participating in another clinical trial with an investigational drug or device, or treated with an investigational drug within 28 days of screening
13. Any of the values that are confirmed on repeat testing as defined in protocol