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

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.

Conditions

• HIV Infections

Interventions

BIOLOGICAL

Vaccine Group A: DNA-HIV-PT123 and AIDSVAX® B/E (weeks 0,4,24,48)

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.

BIOLOGICAL

Vaccine Group B: DNA-HIV-PT123 and CN54gp140+MPLA-L (weeks 0,4), then MVA and CN54gp140+MPLA-L (weeks 24,48)

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).

BIOLOGICAL

Vaccine Group C: Saline placebo (weeks 0,4,24,48)

Sodium Chloride (NaCl) for injection, 0.9%

DRUG

Control PrEP:TDF/FTC once daily (weeks 0-26)

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.

DRUG

Experimental PrEP:TAF/FTC once daily (weeks 0-26)

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.

Sponsors & Collaborators

• Imperial College London

  collaborator OTHER

• University College, London

  collaborator OTHER

• International AIDS Vaccine Initiative

  collaborator NETWORK

• EuroVacc Foundation

  collaborator OTHER

• Medical Research Council, South Africa

  collaborator OTHER

• National Institute for Medical Research, Tanzania

  collaborator OTHER_GOV

• Muhimbili University of Health and Allied Sciences

  collaborator OTHER

• Instituto Nacional de Saúde, Mozambique

  collaborator OTHER_GOV

• Ludwig-Maximilians - University of Munich

  collaborator OTHER

• King's College London

  collaborator OTHER

• Centre Hospitalier Universitaire Vaudois

  collaborator OTHER

• Karolinska Institutet

  collaborator OTHER

• CONRAD

  collaborator OTHER

• Gilead Sciences

  collaborator INDUSTRY

• MRC/UVRI and LSHTM Uganda Research Unit

  lead OTHER

Principal Investigators

• Pontiano Kaleebu, PhD · MRC/UVRI and LSHTM Uganda Resae

• Sheena McCormack, MSc · MRC CTU at UCL

• Jonathan Weber, PhD · Imperial College London

Study Design

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

TRIPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

40 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2020-12-15

Primary Completion

2024-12-31

Completion

2024-12-31

FDA Drug

Yes

Countries

• Uganda

Study Locations