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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04066881
Recruitment Status : Not yet recruiting
First Posted : August 26, 2019
Last Update Posted : August 26, 2019
Sponsor:
Collaborators:
Imperial College London
University College, London
International AIDS Vaccine Initiative
EuroVacc Foundation
Medical Research Council, South Africa
National Institute for Medical Research, Tanzania
Muhimbili University of Health and Allied Sciences
Instituto Nacional de Saúde, Mozambique
Ludwig-Maximilians - University of Munich
King's College London
Centre Hospitalier Universitaire Vaudois
Karolinska Institutet
CONRAD
Gilead Sciences
Information provided by (Responsible Party):
Prof Pontiano Kaleebu, MRC/UVRI Uganda Research Unit on Aids

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.


Condition or disease Intervention/treatment Phase
HIV Infections Biological: Vaccine Group A: DNA-HIV-PT123 and AIDSVAX® B/E (weeks 0,4,24,48) Biological: Vaccine Group B: DNA-HIV-PT123 and CN54gp140+MPLA-L (weeks 0,4), then MVA and CN54gp140+MPLA-L (weeks 24,48) Biological: Vaccine Group C: Saline placebo (weeks 0,4,24,48) Drug: Control PrEP:TDF/FTC once daily (weeks 0-26) Drug: Experimental PrEP:TAF/FTC once daily (weeks 0-26) Phase 2

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 1668 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

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)

Group G: Saline placebo (wks 0,4,24,48)/ TAF/FTC (Descovy) once daily (wks 0-26)

Masking: Triple (Care Provider, Investigator, Outcomes Assessor)
Masking Description:

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.

Primary Purpose: Prevention
Official Title: 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
Estimated Study Start Date : January 2020
Estimated Primary Completion Date : March 2023
Estimated Study Completion Date : March 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Arm Intervention/treatment
Experimental: Group A

278 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)

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.

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.
Other Name: Truvada

Experimental: Group B

278 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)

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).

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.
Other Name: Truvada

Placebo Comparator: Group C:

278 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)

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.
Other Name: Truvada

Active Comparator: Group D

278 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)

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.

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.
Other Name: Descovy

Experimental: Group E

278 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)

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).

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.
Other Name: Descovy

Placebo Comparator: Group G

278 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)

Biological: Vaccine Group C: Saline placebo (weeks 0,4,24,48)
Sodium Chloride (NaCl) for injection, 0.9%

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.
Other Name: Descovy




Primary Outcome Measures :
  1. Incident HIV infection [ Time Frame: after week 26 ]
    HIV acquisition by a participant who completed three immunisations and was HIV negative at week 26.

  2. Incident HIV infection [ Time Frame: week 0-26 ]
    HIV acquisition at or before week 26 by a participant who was HIV negative at enrolment

  3. A clinical decision to discontinue the vaccine regimen for an adverse event that is considered related to product [ Time Frame: week 0-48 ]
    A clinical decision to discontinue the vaccine regimen for an adverse event that is considered related to product

  4. A clinical decision to discontinue PrEP regimen for an adverse event that is considered related to product [ Time Frame: week 0-26 ]
    A clinical decision to discontinue PrEP regimen for an adverse event that is considered related to product


Secondary Outcome Measures :
  1. Grade 3 and worse solicited clinical and laboratory adverse events [ Time Frame: week 0-74 ]
    Grade 3 and worse solicited clinical and laboratory adverse events

  2. Discontinuation or interruption of vaccine regimen [ Time Frame: week 0-74 ]
    A clinical decision to discontinue or interrupt the vaccine regimen for an adverse event that is considered related to product

  3. Discontinuation or interruption of PrEP [ Time Frame: week 0-26 ]
    A clinical decision to discontinue or interrupt the PrEP regimen for an adverse event that is considered related to product

  4. Grade 3 and worse solicited clinical and laboratory adverse events [ Time Frame: within 7 days of receiving vaccine injection ]
    Grade 3 and worse solicited clinical and laboratory adverse events

  5. Serious adverse events [ Time Frame: week 0-74 ]
    Serious adverse events

  6. Other clinical and laboratory adverse events [ Time Frame: week 0-74 ]
    Other clinical and laboratory adverse events

  7. Binding antibodies [ Time Frame: week 0-74 ]
    Binding antibodies to Cn54gp140 and AIDSVAX® B/E gp120

  8. Resistance mutations to tenofovir and emtricitabine [ Time Frame: week 0-74 ]
    Genotypic resistance at HIV seroconversion, focussing on the mutations selected by tenofovir and emtricitabine (codons 65, 70, 184 in reverse transcriptase)

  9. Number of PrEP pills missed [ Time Frame: week 0-26 ]
    Adherence to PrEP assessed by self-report

  10. Tenofovir level in urine [ Time Frame: week 0-26 ]
    Adherence to PrEP assessed by results of point of care urine tests

  11. Tenofovir level in red blood cells [ Time Frame: week 0-26 ]
    Adherence assessed by TFV DP levels measured on DBS in red blood cells

  12. Number of PrEP Pills dispensed [ Time Frame: week 0-26 ]
    Adherence assessed by total number of PrEP pills dispensed



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 40 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04066881


Contacts
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Contact: Bernadette K Nayiga, MSc +25641770400 ext 187 Berna.kalanzi@mrcuganda.org
Contact: Eugene Ruzagira, PhD +256417704000 Eugene.ruzagira@mrcuganda.org

Locations
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Uganda
MRC/UVRI and LSHTM Uganda Research Unit Not yet recruiting
Entebbe, Uganda
Contact: Eugene Ruzagira, PHD    +256417704000    Eugene.ruzagira@mrcuganda.org   
Contact: Bernadette K Nayiga, MSc    +256417704000 ext 187    Berna.kalanzi@mrcuganda.org   
Sponsors and Collaborators
MRC/UVRI Uganda Research Unit on Aids
Imperial College London
University College, London
International AIDS Vaccine Initiative
EuroVacc Foundation
Medical Research Council, South Africa
National Institute for Medical Research, Tanzania
Muhimbili University of Health and Allied Sciences
Instituto Nacional de Saúde, Mozambique
Ludwig-Maximilians - University of Munich
King's College London
Centre Hospitalier Universitaire Vaudois
Karolinska Institutet
CONRAD
Gilead Sciences
Investigators
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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

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Responsible Party: Prof Pontiano Kaleebu, Principal Investigator, MRC/UVRI Uganda Research Unit on Aids
ClinicalTrials.gov Identifier: NCT04066881     History of Changes
Other Study ID Numbers: PV1
First Posted: August 26, 2019    Key Record Dates
Last Update Posted: August 26, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: 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.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (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.


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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Keywords provided by Prof Pontiano Kaleebu, MRC/UVRI Uganda Research Unit on Aids:
HIV
Vaccine
Pre-exposure prophylaxis
Africa
Additional relevant MeSH terms:
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HIV Infections
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination
Vaccines
Immunologic Factors
Physiological Effects of Drugs
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Anti-HIV Agents