A Prophylactic HIV Vaccine Trial to Evaluate the Safety and Immunogenicity of HIV Clade C DREP Alone and in Combination With a Clade C ENV Protein in Healthy HIV-uninfected Adults

NCT04844775 | Completed Phase 1 DMC

• 2 other identifiers: EHVA P01/ANRS VRI082020-005888-31
• Study Type: interventional
• Target: 68
• Locations: 3 countries
• Sites: 4

Brief Summary

EHVA P01 is an international, phase I, prophylactic HIV vaccine trial to evaluate the safety and immunogenicity of HIV Clade C DREP alone and in Combination with a Clade C ENV protein in healthy HIV-uninfected adults.

Conditions

Healthy Adults

Outcome Measures

Primary Outcomes (3)

• Part 1- Dose Escalation- Any adverse reaction that results in a clinical decision to stop immunisations

  Any adverse reaction that results in a clinical decision that no further immunisations can be given

  From week 0 up to Week 4

• Part 2- Randomised Comparison - Any adverse reaction that results in a clinical decision to stop immunisations

  Any adverse reaction that results in a clinical decision that no further immunisations can be given

  From week 0 up to Week 9

• PART 2 Randomised comparison- Total IgG Binding antibody response rate

  1. Env-specific total IgG binding antibody response rates assessed by binding antibody multiplex assay (BAMA) 2. Magnitude of Env-specific total IgG binding antibody responses to HIV-1 Env proteins assessed by binding antibody multiplex assay (BAMA)

  At week 26

Secondary Outcomes (3)

• Part 1- Dose Escalation - Occurrence of Adverse events

  From week 0 to Week 11

• Part 1- Dose Escalation - Binding antibodies to ZM96gp140

  At week 6 and Week 26

• PART 2 Randomised comparison- Total IgG binding antibody response rates

  1, 2 (At week 6); 3,5 (At week 26) and 4,6 (At week 36)

Study Arms (3)

Drep-HIV-PT1 0.2mg and CN54gp140/MPLA-L

EXPERIMENTAL

0.1mL of DREP-HIV-PT1 will be diluted with saline (Sodium Chloride for Injection, 0.9%) and administered intramuscularly (total volume of 0.5mL) in the LEFT deltoid muscle using a needle-free device (Pharmajet Stratis®) 0.4mL of MPLA-L from a vial containing 0.55mL of MPLA-L (25µg/mL) and add this to a vial containing 0.35mL of CN54gp140 (500µg/mL). The vial contents will be mixed by gentle agitation and 0.45mL of will be withdrawn from the vial to make a concentration of 100µg CN54gp140 and 5µg MPLA-L . The combined products will be injected into the RIGHT deltoid muscle using a needle and syringe.

Biological: Drep-HIV-PT1 0.2mg and CN54gp140/MPLA-L

Drep-HIV-PT1 1.0mg and CN54gp140/MPLA-L

EXPERIMENTAL

0.5mL of DREP-HIV-PT1 will be administered intramuscularly in the LEFT deltoid muscle using the a needle-free device (Pharmajet Stratis®) 0.4mL of MPLA-L from a vial containing 0.55mL of MPLA-L (25µg/mL) and add this to a vial containing 0.35mL of CN54gp140 (500µg/mL). The vial contents will be mixed by gentle agitation and 0.45mL of will be withdrawn from the vial to make a concentration of 100µg CN54gp140 and 5µg MPLA-L . The combined products will be injected into the RIGHT deltoid muscle using a needle and syringe.

Biological: DREP-HIV-PT1 1mg and CN54gp140/MPLA-L (see above)

DNA HIV PT123 4mg and CN54gp140/MPLA-L

EXPERIMENTAL

1ml of DNA-HIV-PT123 will be injected into the LEFT deltoid muscle using a needle and syringe. 0.4mL of MPLA-L from a vial containing 0.55mL of MPLA-L (25µg/mL) and add this to a vial containing 0.35mL of CN54gp140 (500µg/mL). The vial contents will be mixed by gentle agitation and 0.45mL of will be withdrawn from the vial to make a concentration of 100µg CN54gp140 and 5µg MPLA-L . The combined products will be injected into the RIGHT deltoid muscle using a needle and syringe.

Biological: DNA-HIV-PT123 4mg and CN54gp140/MPLA-L

Interventions

DNA-HIV-PT123 4mg and CN54gp140/MPLA-L BIOLOGICAL

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. 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.

DNA HIV PT123 4mg and CN54gp140/MPLA-L

Drep-HIV-PT1 0.2mg and CN54gp140/MPLA-L BIOLOGICAL

1. Drep-HIV-PT1 The DREP-HIV-PT1 is a vaccine designed to elicit an immune response against human immunodeficiency virus-1 (HIV-1) and prevent infection by HIV-1 and/or disease caused by HIV-1. It is an alphavirus-based DNA replicon in which the sequences coding for the viral capsid and envelope have been replaced by the sequences encoding HIV-1 gp140 (96ZM651) antigen. 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.

Drep-HIV-PT1 0.2mg and CN54gp140/MPLA-L

DREP-HIV-PT1 1mg and CN54gp140/MPLA-L (see above) BIOLOGICAL

1. Drep-HIV-PT1 1mg (see above) 2. Drep-HIV-PT1 1mg (see above)

Drep-HIV-PT1 1.0mg and CN54gp140/MPLA-L

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy adults aged 18- 55 years on the day of screening
• BMI between 18-30 kg/m2 (inclusive)
• Unlikely to acquire HIV during follow-up
• Willing and able to provide written informed consent
• If female and of childbearing potential\* age and not sterilised, willing to use a highly effective method of contraception from screening until 12 weeks after last injection
• If male and not sterilised, willing to avoid impregnating female partners from screening until 12 weeks after last injection\*\*
• Willing to avoid all other vaccines from 28 days before the first injection through to 28 days after subsequent study injections
• Willing and able to comply with visit schedule and provide blood samples
• Being covered by medical insurance or in National Healthcare System
• A woman will be considered of childbearing potential following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy.
• It is recommended that participants have an up to date vaccination status for any required immunisations including authorised COVID-19 vaccines

You may not qualify if:

• Pregnant or lactating
• Has a significant clinical history, physical finding on clinical examination during screening, or presence of a disease that is active or requires treatment to control it, including cardiac, respiratory, endocrine, metabolic, autoimmune, liver, neurological, oncological, psychiatric, immunosuppresive/immunodeficient or other disorders which in the opinion of the investigator is not compatible with healthy status, may compromise the volunteer's safety, preclude vaccination or compromise interpretation of the immune response to vaccine. Individuals with mild/moderate, well-controlled comorbidities are allowed.
• HIV 1 or 2 infection or indeterminate test at screening
• History of anaphylaxis or angioedema
• History of severe or multiple allergies to drugs or pharmaceutical agents
• Known hypersensitivity to any component of the vaccine formulation used in this trial
• History of severe local or general reaction to vaccination defined as
• local: extensive, indurated redness and swelling involving most of the arm, not resolving within 72 hours
• general: fever \>= 39.5oC within 48 hours; anaphylaxis; bronchospasm; laryngeal oedema; collapse; convulsions or encephalopathy within 72 hours
• Receipt of any experimental vaccine within 5 years from screening.
• Receipt of blood products or immunoglobulins within 18 weeks of screening.
• Receipt any of immunosuppressive agents within 18 weeks of screening by any route other than skin and intranasal.
• Detection of antibodies to hepatitis B \& C
• Participating in another clinical trial with an investigational drug or device, or treated with an investigational drug within 28 days of screening
• Any of the values that are confirmed on repeat testing as defined in protocol

Sponsors & Collaborators

• ANRS, Emerging Infectious Diseases: lead
• Medical Research Council: collaborator
• Henri Mondor University Hospital: collaborator
• Chelsea and Westminster Hospital, UK: collaborator
• EuroVacc Foundation: collaborator
• European Commission: collaborator
• Swiss Government: collaborator
• University College London Hospitals: collaborator
• Imperial College London: collaborator
• Recherche Clinique Paris Descartes Necker Cochin Sainte Anne: collaborator

Study Sites (4)

CIC Cochin

Paris, Paris Cedex 14, 75679, France

Location

Hôpital Henri Mondor

Créteil, Paris, 94010, France

Location

CHUV

Lausanne, Canton of Vaud, 1011, Switzerland

Location

Chelsea and Westminster Hospital

London, SW10 9NH, United Kingdom

Location

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 24, 2021
• First Posted: April 14, 2021
• Study Start: August 5, 2022
• Primary Completion: September 9, 2024
• Study Completion: September 9, 2024
• Last Updated: June 8, 2026

Record last verified: 2026-06

Locations

GB (1); FR (2); CH (1)