A HIV Vaccine Trial in Individuals Who Started Antiretrovirals During Primary or Chronic Infection (EHVA T02)

NCT04120415 | Completed Phase 2 DMC

• 1 other identifier: EHVA T02/ANRS VRI07
• Study Type: interventional
• Target: 2
• Locations: 3 countries
• Sites: 4

Brief Summary

EHVA T02 is an international, phase II, double-blind study to evaluate two experimental arms each compared to placebo control in HIV-1 positive participants to see if either has a clinically relevant impact on viral replication.

Conditions

HIV-1-infection

Outcome Measures

Primary Outcomes (1)

• Area under the HIV RNA curve

  Area under the HIV RNA curve from treatment interruption (scheduled for 18 weeks after entering the trial)

  Time from treatment interruption (scheduled for 18 weeks after entering the trial) to 24 weeks post-treatment interruption

Secondary Outcomes (6)

• Virological outcome measures

  For participants commencing treatment interruption only, critical time points weeks 19 through to to week 42.

• Virological outcome measures

  From randomisation to study completion about 54 weeks

• Virological outcome measures

  From randomisation to study completion about 54 weeks

• Virological outcome measures

  Time from treatment interruption, only in participants commencing treatment interruption, up to 24 weeks after ATI

• Virological outcome measures

  Time from treatment interruption, only in participants commencing treatment interruption, up to 24 weeks after ATI

Other Outcomes (8)

• Safety outcome measures: Grade 3 or worse solicited clinical and laboratory adverse events

  From randomisation to study completion about 54 weeks

• Safety outcome measures: Any adverse event leading to interruption in the vaccine/placebo or vedolizumab/placebo

  From randomisation to study completion about 54 weeks

• Safety outcome measures: Any event that results in resuming treatment during the ATI

  Time form treatment interruption to resuming treatment, up to 24 weeks after ATI

Study Arms (3)

Vaccine and Vedolizumab infusion

EXPERIMENTAL

Vaccine: The vaccine is MVA HIV-B which is a solution of HIV MVA vectors in S08 buffer (10mM Tris/hydrochloride (Tris/HCl), Saccharose 5% (w/v), 10mM Sodium Glutamate (Na Glu), 50mM Sodium Chloride (NaCl), water PPI, pH 8.0). Vedolizumab infusion (Entyvio): Vedolizumab (300mg) is administered as an intravenous infusion (255 ml).

Biological: Vaccine and vedolizumab (Entyvio)

Placebo vaccine and Vedolizumab infusion

EXPERIMENTAL

Placebo vaccine: The placebo for MVA HIV-B to be used in this trial is a solution composed of S08 buffer (as for the MVA vaccine). Vedolizumab infusion (Entyvio): Vedolizumab (300mg) is administered as an intravenous infusion (255 ml)

Biological: Placebo vaccine and vedolizumab infusion (Entyvio)

Placebo vaccine and placebo infusion

PLACEBO COMPARATOR

Placebo vaccine: The placebo for MVA HIV-B to be used in this trial is a solution composed of S08 buffer (as for the MVA vaccine). Placebo infusion: Sodium Chloride (NaCl) 0.9% administered as an intravenous infusion (255ml)

Biological: Placebo vaccine and placebo infusion

Interventions

Vaccine and vedolizumab (Entyvio) BIOLOGICAL

Vaccine and vedolizumab infusion (Entyvio): 0.5ml of MVA HIV-B (1 x 108 pfu/ml) will be administered intramuscularly in the deltoid muscle of the non-dominant upper arm at weeks 0 and 8. Participants will be observed after the injection. Vedolizumab (300mg) is administered as an intravenous infusion (255 ml) over 30 mins in the dominant arm at weeks 10,12,16,20,24,28 and 32. After infusion, the line should be flushed with 30ml of normal saline. Participants will be observed throughout and after the infusion.

Vaccine and Vedolizumab infusion

Placebo vaccine and vedolizumab infusion (Entyvio) BIOLOGICAL

Placebo Vaccine: The placebo for MVA HIV-B to be used is a solution composed of S08 buffer (as for the MVA vaccine) that will be intramuscularly in the deltoid muscle of the non-dominant upper arm at weeks 0 and 8. Participants will be observed after the injection. Vedolizumab infusion (Entyvio): Vedolizumab (300mg) is administered as an intravenous infusion (255 ml) over 30 mins in the dominant arm at weeks 10,12,16,20,24,28 and 32. After infusion, the line should be flushed with 30ml of normal saline. Participants will be observed throughout and after the infusion.

Placebo vaccine and Vedolizumab infusion

Placebo vaccine and placebo infusion BIOLOGICAL

Placebo Vaccine: The placebo for MVA HIV-B to be used is a solution composed of S08 buffer (as for the MVA vaccine) that will be intramuscularly in the deltoid muscle of the non-dominant upper arm at weeks 0 and 8. Participants will be observed after the injection. Placebo infusion (Entyvio): 255ml Sodium Chloride (NaCl) 0.9% bag administered as an intravenous infusion over 30 mins in the dominant arm at weeks 10,12,16,20,24,28 and 32. Participants will be observed throughout and after the infusion.

Placebo vaccine and placebo infusion

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• HIV-1-infected
• Aged 18 - 65 years old on the day of screening
• Weight \>50kg
• Willing and able to provide written informed consent
• Nadir CD4 count \> 300 cells/mm3
• CD4 count at screening \> 500 cells/mm3
• Viral load \<50 copies/ml at screening.
• Started cART after 2009 and on cART for at least one year prior to screening
• Willing to interrupt cART for up to 24 weeks and change cART regimen if required
• If sexually active, willing to use a reliable method of reducing the risk of transmission to their sexual partners during treatment interruption (which could include PrEP for their sexual partners)
• If heterosexually active and able to have children, willing to use a highly effective method of contraception with partner (combined oral contraceptive pill; injectable or implanted contraceptive; IUD/IUS; physiological or anatomical sterility (in self or partner) from 2 weeks before enrolment until 18 weeks after the last injection/infusion
• If women of childbearing potential\*, willing to undergo urine pregnancy tests prior to administration of an injection and an infusion
• Willing to avoid all other vaccines within 4 weeks of scheduled study injections
• Willing and able to comply with visit schedule and provide blood samples
• Being covered by medical insurance or in National Healthcare System

You may not qualify if:

• Pregnant or lactating
• HIV-2 infection (either isolated or associated with HIV-1)
• VL \>200 copies/ml on 2 occasions in the 12 months prior to screening
• Previous interruptions in cART
• Previous virological failures defined by loss of virological suppression with the presence of resistant mutations
• Haemoglobin (Hb \<12g/dL for males, \<11g/dL for females)
• Concomitant or previous conditions that preclude injection of vaccines/infusion of monoclonal antibody and PML in the past
• History of experimental vaccinations against HIV
• Previous treatment with chemotherapy (except for chemotherapy injected into skin lesions for Kaposi's sarcoma)
• Treatment with systemic corticoids or immuno-suppressive agents ongoing or in the 12 weeks prior to randomisation in the trial
• Received natalizumab or rituximab ever in the past
• Received a TNF blocker in the past 60 days
• Administration of an inactivated vaccine within 30 days or a live vaccine within 60 days prior to randomisation
• Presence of a skin condition or marking that precludes inspection of the injection/infusion site
• History of cancer (except basal cellular skin carcinoma or Kaposi's sarcoma)

Sponsors & Collaborators

• ANRS, Emerging Infectious Diseases: lead
• EuroVacc Foundation: collaborator
• European AIDS Treatment Group (EATG): collaborator
• Medical Research Council: collaborator
• University College London Hospitals: collaborator
• University of Liverpool: collaborator
• Erasmus Medical Center: collaborator
• Henri Mondor University Hospital: collaborator
• European Georges Pompidou Hospital: collaborator
• Saint-Louis Hospital, Paris, France: collaborator
• Centre Hospitalier Universitaire Vaudois: collaborator
• Chelsea and Westminster Hospital, UK: collaborator
• Universitätsklinikum Hamburg-Eppendorf: collaborator
• Hospital Clinic of Barcelona: collaborator
• Istituto Nazionale per le Malattie Infettive "Lazzaro Spallanzani" IRCCS: collaborator
• Imperial College London: collaborator
• Institut d'Investigacions Biomèdiques August Pi i Sunyer: collaborator
• European Commission: collaborator
• Swiss Government: collaborator

Study Sites (4)

Service Immunologie clinique et maladies infectieuses, Hôpital Henri Mondor

Paris, Creteil, 94010, France

Location

Hotel Dieu

Paris, 75004, France

Location

Centre d'Immunothérapie et Vaccinologie, CHUV

Lausanne, Canton of Vaud, 1011, Switzerland

Location

St Stephens Centre, Chelsea & Westminster Hospital

London, SW10 9NH, United Kingdom

Location

MeSH Terms

Interventions

Vaccines; vedolizumab

Intervention Hierarchy (Ancestors)

Biological Products; Complex Mixtures

Study Officials

• Yves Levy, MD

  Institut National de la Santé Et de la Recherche Médicale, France

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 30, 2019
• First Posted: October 9, 2019
• Study Start: June 21, 2022
• Primary Completion: July 12, 2023
• Study Completion: July 12, 2023
• Last Updated: August 4, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will not share

Locations

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