A Combination Efficacy Study in Africa of Two DNA-MVA-Env Protein or DNA-Env Protein HIV-1 Vaccine Regimens With PrEP
PrEPVacc
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
1 other identifier
interventional
1,512
1 country
1
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2 hiv-infections
Started Dec 2020
Typical duration for phase_2 hiv-infections
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 8, 2019
CompletedFirst Posted
Study publicly available on registry
August 26, 2019
CompletedStudy Start
First participant enrolled
December 15, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 31, 2024
CompletedStudy Completion
Last participant's last visit for all outcomes
December 31, 2024
CompletedJanuary 22, 2025
January 1, 2025
4 years
August 8, 2019
January 20, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (4)
Incident HIV infection
HIV acquisition by a participant who completed three immunisations and was HIV negative at week 26.
after week 26
Incident HIV infection
HIV acquisition at or before week 26 by a participant who was HIV negative at enrolment
week 0-26
A clinical decision to discontinue the vaccine regimen for an adverse event that is considered related to product
A clinical decision to discontinue the vaccine regimen for an adverse event that is considered related to product
week 0-48
A clinical decision to discontinue PrEP regimen for an adverse event that is considered related to product
A clinical decision to discontinue PrEP regimen for an adverse event that is considered related to product
week 0-26
Secondary Outcomes (12)
Grade 3 and worse solicited clinical and laboratory adverse events
week 0-74
Discontinuation or interruption of vaccine regimen
week 0-74
Discontinuation or interruption of PrEP
week 0-26
Grade 3 and worse solicited clinical and laboratory adverse events
within 7 days of receiving vaccine injection
Serious adverse events
week 0-74
- +7 more secondary outcomes
Study Arms (6)
Group A
EXPERIMENTAL278 participants will receive DNA-HIV-PT123 vaccine and AIDSVAX® B/E protein at weeks 0, 4, 24 and 48. 1ml of DNA-HIV-PT123 will be injected into the deltoid muscle of the left upper arm 1ml of AIDSVAX® B/E will be injected into the deltoid muscle of the right arm 1 tab of Truvada (0-26 weeks)
Group B
EXPERIMENTAL278 participants will receive DNA-HIV-PT123 and CN54gp140+MPLA-L at weeks 0 and 4, then MVA and CN54gp140+MPLA-L at weeks 24 and 48 1ml of DNA-HIV-PT123 will be injected into the deltoid muscle of the left upper arm 1ml (1x108 pfu) of MVA will be injected into the deltoid muscle of the left upper arm 0.4mL containing a mixture of 100mcg CN54gp140 and 5mcg MPLA-L will be injected into the deltoid muscle of the right upper arm 1 tab of Truvada (0-26 weeks)
Group C:
PLACEBO COMPARATOR278 participants will receive Sodium Chloride 0.9% (Normal Saline) placebo at weeks 0,4,24, and 48 The volume will be matched to the vaccine at 1ml for DNA, MVA and AIDSVAX® B/E, but 0.4ml for CN54gp140 in MPLA-L. Participants will be randomly divided in a 1:1 ratio to receive 1ml in each arm at the four timepoints or 1ml in the left arm and 0.4ml in the right arm at the four timepoints. 1 tab of Truvada (0-26 weeks)
Group D
ACTIVE COMPARATOR278 participants will receive DNA-HIV-PT123 vaccine and AIDSVAX® B/E protein at weeks 0, 4, 24 and 48. 1ml of DNA-HIV-PT123 will be injected into the deltoid muscle of the left upper arm 1ml of AIDSVAX® B/E will be injected into the deltoid muscle of the right arm 1 tab of Descovy (0-26 weeks)
Group E
EXPERIMENTAL278 participants will receive DNA-HIV-PT123 and CN54gp140+MPLA-L at weeks 0 and 4, then MVA and CN54gp140+MPLA-L at weeks 24 and 48 1ml of DNA-HIV-PT123 will be injected into the deltoid muscle of the left upper arm 1ml (1x108 pfu) of MVA will be injected into the deltoid muscle of the left upper arm 0.4mL containing a mixture of 100mcg CN54gp140 and 5mcg MPLA-L will be injected into the deltoid muscle of the right upper arm 1 tab of Descovy (0-26 weeks)
Group G
PLACEBO COMPARATOR278 participants will receive Sodium Chloride 0.9% (Normal Saline) placebo at weeks 0,4,24, and 48 The volume will be matched to the vaccine at 1ml for DNA, MVA and AIDSVAX® B/E, but 0.4ml for CN54gp140 in MPLA-L. Participants will be randomly divided in a 1:1 ratio to receive 1ml in each arm at the four timepoints or 1ml in the left arm and 0.4ml in the right arm at the four timepoints. 1 tab of Descovy (0-26 weeks)
Interventions
1. DNA-HIV-PT123 HIV vaccine includes three DNA plasmids that encode clade C ZM96 Gag, clade C ZM96 Env, and CN54 Pol-Nef. 2. AIDSVAX® B/E is a bivalent HIV gp120 glycoprotein encompassing both subtype B (MN) and subtype E (A244) proteins that are adsorbed onto 600mcg of aluminum hydroxide gel suspension as adjuvant.
1. DNA-HIV-PT123 (see above) 2. CN54gp140+MPLA-L. Recombinant CN54gp140 is a HIV-1 envelope protein from the clade C strain 97/CN/54 isolate, which comprises a sequence of 634 amino acids. MPLA is a non-toxic version of LipoPolySaccharide (LPS), which is isolated from the LPS lipid A region of Salmonella Minnesota R595 and retains the immune-stimulatory properties of LPS, but exhibits low toxicity. 3. MVA-CMDR (Modified Vaccinia Ankara-Chiang Mai Double Recombinant) is a non-replicating, highly attenuated strain of Vaccina virus that has been genetically engineered to express the HIV-1 genes envgp160 CM235 Subtype E and gag and pol CM240 Subtype A (integrase-deleted and reverse transcriptase non-functional).
Sodium Chloride (NaCl) for injection, 0.9%
Each tablet of Truvada contains 245mg of tenofovir disoproxil (TDF) and 200mg of emtricitabine (FTC), both of which are nucleot/side analogue HIV-1 reverse transcriptase inhibitors.
Each tablet of Descovy contains 25mg of tenofovir alfenamide (TAF) and 200mg of emtricitabine (FTC), both of which are nucleot/side analogue HIV-1 reverse transcriptase inhibitors.
Eligibility Criteria
You may qualify if:
- HIV uninfected adults aged between 18 and 40 years old on the day of screening
- Willing and able to provide informed consent prior to participation
- Willing and able to comply with the visit schedule and provide blood, urine and other samples at the required time points
- Home address accessible for visiting and intending to remain within the recruitment area for at least 82 weeks from screening
- Likely to be at risk from exposure to HIV during follow up
- Willing to undergo HIV testing, receive HIV test results and risk reduction counselling which includes promotion of PrEP and condoms
- 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
- If male and not sterilised, willing to avoid impregnating female partners from screening until 18 weeks after the last injection
You may not qualify if:
- HIV infection or indeterminate HIV result at screening or enrolment
- Hepatitis B surface antigen positive
- If female, currently pregnant (evidence from positive serum or urine pregnancy test), or lactating
- Participating in another biomedical research study or in receipt of a live vaccine within 30 days prior to randomisation
- Participation in a previous HIV vaccine or HIV immunotherapy trial
- Receiving blood products or immunoglobulins within 12 weeks of screening
- 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
- 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
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- MRC/UVRI and LSHTM Uganda Research Unitlead
- Imperial College Londoncollaborator
- University College, Londoncollaborator
- International AIDS Vaccine Initiativecollaborator
- EuroVacc Foundationcollaborator
- Medical Research Council, South Africacollaborator
- National Institute for Medical Research, Tanzaniacollaborator
- Muhimbili University of Health and Allied Sciencescollaborator
- Instituto Nacional de Saúde, Mozambiquecollaborator
- Ludwig-Maximilians - University of Munichcollaborator
- King's College Londoncollaborator
- Centre Hospitalier Universitaire Vaudoiscollaborator
- Karolinska Institutetcollaborator
- CONRADcollaborator
- Gilead Sciencescollaborator
Study Sites (1)
MRC/UVRI and LSHTM Uganda Research Unit
Entebbe, Uganda
Related Publications (3)
Ambikile JS, Tarimo EAM, Iseselo MK, Lukumay G, Munseri P, Bakari M, Lyamuya E, Aboud S, Kawuma R, Seeley J. The experience of trial participation disclosure among sex workers in a phase IIb HIV vaccine trial: A qualitative study in urban Tanzania. PLOS Glob Public Health. 2025 Nov 19;5(11):e0005511. doi: 10.1371/journal.pgph.0005511. eCollection 2025.
PMID: 41259346DERIVEDChimukuche RS, Shandu L, Zulu S, Khanyile P, Singh N, Gaffoor Z, Kawuma R, McCormack S, Seeley J; PrEPVacc Study Group. HIV risk perception, trust and PrEP adherence among participants in an HIV prevention trial: a qualitative longitudinal study, South Africa. BMJ Open. 2025 Apr 23;15(4):e086742. doi: 10.1136/bmjopen-2024-086742.
PMID: 40268488DERIVEDChimukuche RS, Kawuma R, Mahapa N, Mkhwanazi S, Singh N, Siva S, Ruzagira E, Seeley J; PrEPVacc Study Group. Examining oral pre-exposure prophylaxis (PrEP) literacy among participants in an HIV vaccine trial preparedness cohort study. BMC Health Serv Res. 2022 Nov 10;22(1):1336. doi: 10.1186/s12913-022-08730-8.
PMID: 36357877DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Pontiano Kaleebu, PhD
MRC/UVRI and LSHTM Uganda Resae
- STUDY CHAIR
Sheena McCormack, MSc
MRC CTU at UCL
- STUDY DIRECTOR
Jonathan Weber, PhD
Imperial College London
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- TRIPLE
- Who Masked
- CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Masking Details
- 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. Clinic 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. The 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.
- Purpose
- PREVENTION
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 8, 2019
First Posted
August 26, 2019
Study Start
December 15, 2020
Primary Completion
December 31, 2024
Study Completion
December 31, 2024
Last Updated
January 22, 2025
Record last verified: 2025-01
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF, CSR
- Time Frame
- The approved versions of the study protocol and global informed consent form will be in the public domain throughout. The Statistical Analysis Plan will be in the public domain prior to database lock. The clinical study report will be available a year after the last participant visit.
- Access Criteria
- The approved protocols and final version of the SAP will be in the public domain. The clinical study report will be available on request.
The investigators will ensure that optimal use is made of the data generated in this trial through a controlled access approach to data sharing. Access will be controlled to ensure that there is a scientific rationale for the data, that no data are released that could compromise the ongoing trial, that the appropriate consent is in place, that an appropriate agreement is in place for secure transfer and storage, and that resources required to process data release are adequate.