A Combination Efficacy Study in Africa of Two DNA-MVA-Env Protein or DNA-Env Protein HIV-1 Vaccine Regimens With PrEP

• Status: Not yet recruiting
• Trial end date: 2023-03-01
• Target enrollment: 0
• Participant gender: All

Summary

This international, multi-centre, double-blind vaccine study is a three-arm prospective 1:1:1 randomisation comparing each of two experimental combination vaccine regimens i.e. DNA/AIDSVAX (weeks 0,4,24,48) and DNA/CN54gp140 (weeks 0,4) + MVA/CN54gp140 (weeks 24,48) with placebo control. There will be a concurrent open-label 1:1 randomisation to compare daily TAF/FTC (week 0-26) to daily TDF/FTC (weeks 0-26) as pre-exposure prophylaxis.

The study aims to randomise up to 1668 eligible adults (18-40 years) through collaborating clinical research centres in 4 countries (Mozambique; South Africa; Tanzania; and Uganda). Each participant will be followed for a minimum of 74 weeks after enrolment.

The trial is designed to detect a reduction in HIV incidence that has public health relevance sufficient to justify implementation of the combination vaccine regimen. In light of the high level of effectiveness demonstrated in the PrEP trials (up to 86% reduction in HIV), this trial is powered to detect a protective vaccine efficacy of 70% at the final analysis.

The PrEP component will determine whether the effectiveness of TAF/FTC is unacceptably lower than the effectiveness of TDF/FTC.

• Phase: Phase 2
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: MRC/UVRI and LSHTM Uganda Research Unit; MRC/UVRI Uganda Research Unit on Aids
• Collaborators: Centre Hospitalier Universitaire Vaudois; CONRAD; EuroVacc Foundation; Gilead Sciences; Imperial College London; Instituto Nacional de Saúde, Mozambique; International AIDS Vaccine Initiative; Karolinska Institutet; King's College London; Ludwig-Maximilians - University of Munich; Medical Research Council, South Africa; Muhimbili University of Health and Allied Sciences; National Institute for Medical Research, Tanzania; University College, London
• Treatments: Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Vaccines

Criteria

Inclusion criteria

1. HIV uninfected adults aged between 18 and 40 years old on the day of screening

2. Willing and able to provide informed consent prior to participation

3. Willing and able to comply with the visit schedule and provide blood, urine and other samples at the required time points

4. Home address accessible for visiting and intending to remain within the recruitment area for at least 82 weeks from screening

5. Likely to be at risk from exposure to HIV during follow up

6. Willing to undergo HIV testing, receive HIV test results and risk reduction counselling which includes promotion of PrEP and condoms

7. If female, of child-bearing age and not sterilised, willing to use a highly effective method of contraception from screening until 18 weeks after the last injection

8. If male and not sterilised, willing to avoid impregnating female partners from screening until 18 weeks after the last injection

Exclusion criteria

1. HIV infection or indeterminate HIV result at screening or enrolment

2. Hepatitis B surface antigen positive

3. If female, currently pregnant (evidence from positive serum or urine pregnancy test), or lactating

4. Participating in another biomedical research study or in receipt of a live vaccine within 30 days prior to randomisation

5. Participation in a previous HIV vaccine or HIV immunotherapy trial

6. Receiving blood products or immunoglobulins within 12 weeks of screening

7. Known hypersensitivity to any component of the vaccine formulations used in this trial or history of severe or multiple allergies to vaccines, drugs or pharmaceutical agents

8. Presence of a systemic disease at the time of randomisation or history of chronic illness that in the opinion of the investigator may compromise the participant's safety, preclude vaccination or compromise an immune response to vaccine

9. Abnormalities in routine laboratory parameters (Hb, creatinine, AST/ALT, alkaline phosphatase, total Bilirubin and glucose) of Grade 2 and above using the DAIDS toxicity table, version 2.1 July 2017 or estimated glomerular filtration rate less than 50ml/min