A Phase IIb Three-arm, Two-stage HIV Prophylactic Vaccine Trial With a Second Randomisation to Compare TAF/FTC to TDF/FTC as Pre-exposure Prophylaxis

RGPK190803

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.

2020-12-15

2024-12-31

2024-12-31

Early phase I

1668

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

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE2'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'PARALLEL', 'interventionModelDescription': 'Group A: DNA-HIV-PT123/AIDSVAX B/E®/TDF/FTC (Truvada) once daily (wks 0-26) Group B: DNA-HIV-PT123 and CN54gp140+MPLA-L (wks 0,4), then MVA-CMDR and CN54gp140+MPLA-L/ TDF/FTC(Truvada) once daily (wks 0-26) Group C: Saline placebo (wks 0,4,24,48)/ TDF/FTC (Truvada) once daily (wks 0-26) Group D: DNA-HIV-PT123/AIDSVAX B/E®/ TAF/FTC (Descovy) once daily (wks 0-26) Group E: DNA-HIV-PT123 and CN54gp140+MPLA-L (wks 0,4), then MVA-CMDR and CN54gp140+MPLA-L/ TAF/FTC (Descovy) once daily (wks 0-26) Group F: Saline placebo (wks 0,4,24,48)/ TAF/FTC (Descovy) once daily (wks 0-26)\n\nGroup G: Saline placebo (wks 0,4,24,48)/ TAF/FTC (Descovy) once daily (wks 0-26)', 'primaryPurpose': 'PREVENTION', 'maskingInfo': {'masking': 'TRIPLE', 'maskingDescription': 'The vaccine component of PrEPVacc is placebo-controlled. Study staff, participants, laboratory staff and clinical staff assessing safety outcomes will not know who has been allocated vaccine or placebo, but pharmacy staff will know. The committee assessing the efficacy endpoints will not see the allocation in the first instance. The IDMC and statistical staff preparing the closed reports for the IDMC will also know the allocation.\n\nClinic staff will see the difference in volume between CN54gp140 in MPLA-L/matched placebo (0.4ml) and DNA-HIV-PT123/matched placebo (1ml) due to the position of the plunger, but they will not be able to differentiate between active and placebo.\n\nThe randomisation to control PrEP: experimental PrEP is 1:1 and all study staff and participants will know the allocation after randomisation as this is open-label.', 'whoMasked': ['CARE_PROVIDER', 'INVESTIGATOR', 'OUTCOMES_ASSESSOR']}}, 'enrollmentInfo': {'count': 1668, 'type': 'ESTIMATED'}}

2023-10-24