Clinical Trials

MainTitle

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

This study is not yet open for participant recruitment. (see Contacts and Locations)

Verified October 2019 by French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)

Sponsor
French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)

Collaborator
EuroVacc Foundation
European AIDS Treatment Group (EATG)
Medical Research Council
University College London, UK.
University of Liverpool
Erasmus Medical Center
Henri Mondor University Hospital
European Georges Pompidou Hospital
Saint-Louis Hospital, Paris, France
Centre Hospitalier Universitaire Vaudois
Chelsea and Westminster Hospital, UK
Universitätsklinikum Hamburg-Eppendorf
Hospital Clinic of Barcelona
Istituto Nazionale Malattie Infettive Lazaro Spallanzani
Imperial College London
Institut d'Investigacions Biomèdiques August Pi i Sunyer
European Commission
Swiss Government

Information provided by (Responsible Party)
French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
ClinicalTrials.gov Identifier
NCT04120415

First received: September 30, 2019
Last updated: October 9, 2019
Last Verified: October 2019
History of Changes
Purpose

Purpose

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.

Condition Intervention Phase
HIV-1-infection

Biological : Vaccine and vedolizumab (Entyvio)
Biological : Placebo vaccine and vedolizumab infusion (Entyvio)
Biological : Placebo vaccine and placebo infusion
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: EHVA T02 (European HIV Vaccine Alliance Therapeutic Trial 02)/ANRS VRI07: A Phase II Randomised, Placebo-controlled Trial of Vedolizumab With or Without Therapeutic HIV MVA Vaccine in Individuals Who Started Antiretrovirals During Primary or Chronic Infection

Further study details as provided by French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS):

Primary Outcome Measures

  • Area under the HIV RNA curve [ Time Frame: Time from treatment interruption (scheduled for 18 weeks after entering the trial) to 24 weeks post-treatment interruption ]
    Area under the HIV RNA curve from treatment interruption (scheduled for 18 weeks after entering the trial)
Secondary Outcome Measures:
  • Virological outcome measures [ Time Frame: For participants commencing treatment interruption only, critical time points weeks 19 through to to week 42. ]
    Time from treatment interruption (scheduled for 18 weeks after entering the trial) to the earliest of reaching HIV RNA ≥ 100 000 copies/ml (confirmed on a separate sample) or resuming antiretroviral therapy for any reason over a period of 24 weeks.
  • Virological outcome measures [ Time Frame: From randomisation to study completion about 54 weeks ]
    Level of HIV total RNA
  • Virological outcome measures [ Time Frame: From randomisation to study completion about 54 weeks ]
    Cell Associated (CA) HIV RNA Quantification
  • Virological outcome measures [ Time Frame: Time from treatment interruption, only in participants commencing treatment interruption, up to 24 weeks after ATI ]
    First local maximum (peak) level of HIV total RNA during treatment interruption
  • Virological outcome measures [ Time Frame: Time from treatment interruption, only in participants commencing treatment interruption, up to 24 weeks after ATI ]
    Rate of increase of HIV total RNA between the last measure below the lower detection and the first local maximum
  • Virological outcome measures [ Time Frame: Time from treatment interruption, only in participants commencing treatment interruption, up to 24 weeks after ATI ]
    Setpoint (two stable measures following a transient increase of HIV RNA)
Other Outcome Measures:
  • Safety outcome measures: Grade 3 or worse solicited clinical and laboratory adverse events [ Time Frame: From randomisation to study completion about 54 weeks ]
    Occurrence of grade 3 or worse solicited clinical and laboratory adverse events
  • Safety outcome measures: Any adverse event leading to interruption in the vaccine/placebo or vedolizumab/placebo [ Time Frame: From randomisation to study completion about 54 weeks ]
    Occurrence of any adverse event leading to interruption in the vaccine/placebo or vedolizumab/placebo
  • Safety outcome measures: Any event that results in resuming treatment during the ATI [ Time Frame: Time form treatment interruption to resuming treatment, up to 24 weeks after ATI ]
    Occurrence of any event that results in resuming treatment during the ATI
  • Safety outcome measures: Serious Adverse Events [ Time Frame: From randomisation until 30 days after the last protocol visit ]
    Occurrence of Serious Adverse Events
  • Safety outcome measures: Other clinical and laboratory adverse events [ Time Frame: From randomisation to study completion about 54 weeks ]
    Occurrence of other clinical and laboratory adverse events
  • Safety outcome measures: Change in absolute CD4 [ Time Frame: From randomisation to study completion about 54 weeks ]
    Observation of change in absolute CD4 count
  • Safety outcome measures: Time to VL suppression after restarting cART [ Time Frame: From randomisation to VL suppression (= VL is undetectable (<50copies/ml)) after restarting cART until the participant returns to an undetectable viral load, about 54 weeks] ]
    Time to VL suppression after restarting cART
  • Exploratory Immunological outcome measures: Characterization of vaccine induced CD4 and CD8 T-cell produced cytokine profile [ Time Frame: From randomisation to study completion about 54 weeks ]
    Observation of vaccine induced CD4 and CD8 T-cell produced cytokines by flow cytometry

Estimated Enrollment: 69
Study Start Date: November 2019
Estimated Study Completion Date: December 2021
Estimated Primary Completion Date: June 2021 (Final data collection date for primary outcome measure)

Arms Assigned Interventions
Experimental: Vaccine and Vedolizumab infusion
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)
    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.

    Experimental: Placebo vaccine and Vedolizumab infusion
    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:
      • 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 Comparator: Placebo vaccine and placebo infusion
      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
        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.

        Detailed Description:

        Screening will take place during the 6 weeks prior to randomisation. Eligible participants will be enrolled at week 0 and randomised to MVA HIV-B vaccine followed by vedolizumab, vedolizumab + placebo vaccine, or placebo vaccine + placebo infusions.
        Participants will be randomised at each centre through web-based randomisation after entering the eligibility criteria. There will be two strata: one for those who started treatment during primary infection, and one for those who started treatment during chronic infection.
        69 eligible individuals from collaborating European Countries will be enrolled, aiming for approximately half who started cART in primary infection and half who started in chronic infection. Participants continue from the screening visit (up to 6 weeks before enrolment) to the last visit, a maximum of 60 weeks (around 14 months), although follow-up will continue through to the time when virus is fully suppressed.
        Treatment will be interrupted at week 18 and resumed when the viral load is confirmed to have rebounded to ≥100,000 copies/ml, or the CD4 falls to ≤350 cells/mm3, confirmed, or there is evidence of disease progression, or they have completed 24 weeks of treatment interruption.

        Eligibility

        Eligibility

        Ages Eligible for Study: 18 Years to 65 Years  
        Sexes Eligible for Study: All  
        Accepts Healthy Volunteers: No  

        Criteria

        Inclusion Criteria:

        1. HIV-1-infected
        2. Aged 18 - 65 years old on the day of screening
        3. Weight >50kg
        4. Willing and able to provide written informed consent
        5. Nadir CD4 count > 300 cells/mm3
        6. CD4 count at screening > 500 cells/mm3
        7. Viral load <50 copies/ml at screening.
        8. Started cART after 2009 and on cART for at least one year prior to screening
        9. Willing to interrupt cART for up to 24 weeks and change cART regimen if required
        10. 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)
        11. 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
        12. If women of childbearing potential*, willing to undergo urine pregnancy tests prior to administration of an injection and an infusion
        13. Willing to avoid all other vaccines within 4 weeks of scheduled study injections
        14. Willing and able to comply with visit schedule and provide blood samples
        15. 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.

      • Exclusion Criteria:
      • 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)
      • History of significant neurological disease or cardiovascular disease (angina, myocardial infarction, transient ischemic attack, stroke); participants with controlled blood pressure are eligible
      • History of clinical autoimmune disease
      • Ongoing diseases including uncontrolled active severe infection, cardiac, pulmonary (excluding mild asthma), thyroid, renal or neurological (peripheral or central) diseases
      • Active or latent tuberculosis (unless prophylaxis in past as per local practice) - (participant must be screened for tuberculosis before starting infusions, according to routine practice)
      • Presence of pathogenic bacteria or parasites in faeces at screening
      • Participating in another biomedical research study within 30 days of randomisation
      • Known hypersensitivity to any component of the vaccine formulation used in this trial including eggs or have severe or multiple allergies to drugs or pharmaceutical agents, or any hypersensitivity to the active substance or to any of the excipients of vedolizumab.
      • Liver disease including hepatitis B (surface antigen positive) or hepatitis C (antigen or PCR positive)
      • A clinically significant abnormality on ECG
      • Hypernatraemia or hyperchloraemia
      • History of severe local or general reaction to vaccination defined as
        1. local: extensive, indurated redness and swelling involving most of the arm, not resolving within 72 hours
        2. general: fever >= 39.5oC within 48 hours; anaphylaxis; bronchospasm; laryngeal oedema; collapse; convulsions or encephalopathy within 72 hours
      • Grade 2 or worse routine laboratory parameters. Hyperbilirubinaemia to be considered an exclusion criterion only when confirmed to be conjugated bilirubinaemia

        contacts and locations

        Contacts and Locations

        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, see Learn About Clinical Studies.

        Please refer to this study by its ClinicalTrials.gov identifier: NCT04120415

        Contacts

        Contact:   Aminata Sy 0044 (0)20 7670 4737 a.sy@ucl.ac.uk
        Contact:   Elizabeth Brodnicki 0044 (0)20 7670 4783 e.brodnicki@ucl.ac.uk

        Sponsors and Collaborators

        French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
        EuroVacc Foundation
        European AIDS Treatment Group (EATG)
        Medical Research Council
        University College London, UK.
        University of Liverpool
        Erasmus Medical Center
        Henri Mondor University Hospital
        European Georges Pompidou Hospital
        Saint-Louis Hospital, Paris, France
        Centre Hospitalier Universitaire Vaudois
        Chelsea and Westminster Hospital, UK
        Universitätsklinikum Hamburg-Eppendorf
        Hospital Clinic of Barcelona
        Istituto Nazionale Malattie Infettive Lazaro Spallanzani
        Imperial College London
        Institut d'Investigacions Biomèdiques August Pi i Sunyer
        European Commission
        Swiss Government

        Investigators

        Study Director: Yves Levy, MD Institut National de la Santé Et de la Recherche Médicale, France
        More Information

        More Information


        Responsible Party: French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)  
        ClinicalTrials.gov Identifier: NCT04120415   History of Changes  
        Other Study ID Numbers: EHVA T02/ANRS VRI07  
        Study First Received: September 30, 2019  
        Last Updated: October 9, 2019  
        Individual Participant Data    
        Plan to Share IPD: No  

        Studies a U.S. FDA-regulated Drug Product: No  
        Studies a U.S. FDA-regulated Device Product: No  

        Additional relevant MeSH terms:
        Infection
        Communicable Diseases
        Vedolizumab
        Vaccines

        ClinicalTrials.gov processed this data on June 02, 2020
        This information is provided by ClinicalTrials.gov.