An HIV Vaccine Trial in Individuals Who Started ART During Primary or Chronic Infection

NCT02972450 | Terminated Phase 1 DMC

• 1 other identifier: EHVA T01/ANRS VRI05
• Study Type: interventional
• Target: 1
• Locations: 2 countries
• Sites: 2

Brief Summary

EVHA T01 is an international, phase I/II, multicentre, multi-stage, double-blind study that will evaluate at least three experimental arms compared to placebo control in HIV-1 infected participants to see if one or more has a clinically relevant impact on the control of viral replication.

Conditions

HIV-1-infection

Outcome Measures

Primary Outcomes (2)

• Efficacy: Time from treatment interruption to the earliest of reaching HIV RNA ≥ 10,000 copies/ml or resuming antiretroviral therapy for any reason over a period of 24 weeks.

  Time from treatment interruption (scheduled for 12 weeks after completing the immunisation schedule) to the earliest of reaching HIV RNA ≥ 10,000 copies/ml or resuming antiretroviral therapy for any reason over a period of 24 weeks.

• Safety: A clinical decision to discontinue the regimen for an adverse event that is considered related to product

  From randomisation

Secondary Outcomes (6)

• Grade 3 and worse solicited clinical and laboratory adverse events

  From randomisation to study completion, about 60 weeks.

• Any event leading to interruption in the vaccine schedule

  From randomisation to study completion, about 60 weeks.

• Any event that results in resuming treatment during the ATI

  From randomisation to study completion, about 60 weeks.

• Serious Adverse Events

  From randomisation to 30 days after the last protocol visit

• Other clinical and laboratory adverse events

  From randomisation to study completion, about 60 weeks.

Other Outcomes (2)

• Secondary Immunological Outcomes

  From randomisation

• Secondary Virological efficacy outcome measures

  From randomisation

Study Arms (4)

Injection only: Active:placebo (3:1)

EXPERIMENTAL

GTU-MultiHIV B-clade + MVA HIV-B: GTU-MultiHIV B-clade - 2 mg of DNA in 1ml encoding a multi HIV antigen (synthetic fusion protein) administered intramuscularly into the non-dominant deltoid muscle at weeks 0 and 4 and MVA HIV-B 0.5ml(1 x108 pfu/ml) MVA encoding the full-length codon-optimized sequence of Gag administered intramuscularly into the non-dominant deltoid muscle at week 12.

Biological: GTU-MultiHIV B-clade vaccine + MVA HIV-B HIV vaccine; Biological: GTU-MultiHIV B-clade vaccine + MVA HIV-B HIV vaccine+ Vedolizumab

Infusion only: Active:placebo (3:1)

EXPERIMENTAL

Vedolizumab will be administered in the participant's dominant arm as an intravenous infusion over 30 mins.

Drug: Vedolizumab 300 MG [Entyvio]

Injection and Infusion: Active:placebo (3:1)

EXPERIMENTAL

GTU-MultiHIV B-clade + MVA HIV-B + Vedolizumab

Biological: GTU-MultiHIV B-clade vaccine + MVA HIV-B HIV vaccine; Biological: GTU-MultiHIV B-clade vaccine + MVA HIV-B HIV vaccine+ Vedolizumab; Drug: Vedolizumab 300 MG [Entyvio]

Placebo

PLACEBO COMPARATOR

Placebo1 for DNA: Sodium chloride for injection, 0.9% in 1ml administered intramuscularly into the non-dominant deltoid muscle at weeks 0 and 4. Placebo 2 for MVA: S08 buffer in 0.5ml administered intramuscularly into the non-dominant deltoid muscle at week 12. Placebo for mAb: Sodium Chloride (NaCl) for infusion, 0.9% in 250 ml infusion bags.

Other: Placebo

Interventions

GTU-MultiHIV B-clade vaccine + MVA HIV-B HIV vaccine BIOLOGICAL

The vaccine is a solution of HIV MVA vectors (see section 1.3.2) 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). 0.5ml of ANRS MVA HIV-B (1 x 108 pfu/ml) or placebo for MVA (S8 buffer) will be administered intramuscularly in the deltoid muscle of the non-dominant upper arm. Participants will be observed for one hour after the injection.

Injection and Infusion: Active:placebo (3:1); Injection only: Active:placebo (3:1)

GTU-MultiHIV B-clade vaccine + MVA HIV-B HIV vaccine+ Vedolizumab BIOLOGICAL

The vaccine is a solution of HIV MVA vectors (see section 1.3.2) 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). 0.5ml of ANRS MVA HIV-B (1 x 108 pfu/ml) or placebo for MVA (S8 buffer) will be administered intramuscularly in the deltoid muscle of the non-dominant upper arm. Participants will be observed for one hour after the injection. Vedolizumab is administered as an intravenous infusion over 30 mins in the dominant arm. After infusion, the line should be flushed with 30mls of normal saline.

Injection and Infusion: Active:placebo (3:1); Injection only: Active:placebo (3:1)

Vedolizumab 300 MG [Entyvio] DRUG

Vedolizumab is administered as an intravenous infusion over 30 mins in the dominant arm. After infusion, the line should be flushed with 30mls of normal saline.

Infusion only: Active:placebo (3:1); Injection and Infusion: Active:placebo (3:1)

Placebo OTHER

Placebo for MVA it is a solution composed of S08 buffer (as for the MVA vaccine) that will be administered intramuscularly in the deltoid muscle of the non-dominant upper arm. Participants will be observed for one hour after the injection. Placebo for GTU-MultiHIV B-clade vaccine: Sodium Chloride (NaCl) for infusion, 0.9%. Placebo for Vedolizumab: Sodium Chloride (NaCl) for infusion, 0.9% in 250 ml infusion bags.

Placebo

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 24weeks 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 or 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 previous 12 weeks before 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
• European Commission: collaborator
• Swiss Government: collaborator
• Medical Research Council: collaborator
• FIT Biotech Ltd.: collaborator
• Fred Hutchinson Cancer Center: collaborator
• University College, London: collaborator
• Centre Hospitalier Universitaire Vaudois: collaborator
• Imperial College London: collaborator
• Istituto Nazionale per le Malattie Infettive "Lazzaro Spallanzani" IRCCS: collaborator
• Universitätsklinikum Hamburg-Eppendorf: collaborator
• Institut d'Investigacions Biomèdiques August Pi i Sunyer: collaborator
• Henri Mondor University Hospital: collaborator
• European Georges Pompidou Hospital: collaborator
• Saint-Louis Hospital, Paris, France: collaborator

Study Sites (2)

CHUV

Lausanne, 1011, Switzerland

Location

Chelsea & Westminster Hospital

London, SW10 9NH, United Kingdom

Location

MeSH Terms

Interventions

vedolizumab

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 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 10, 2016
• First Posted: November 23, 2016
• Study Start: February 20, 2019
• Primary Completion: July 11, 2019
• Study Completion: July 11, 2019
• Last Updated: August 29, 2019

Record last verified: 2019-08

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1); CH (1)