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An HIV Vaccine Trial in Individuals Who Started ART During Primary or Chronic Infection (EHVAT01)

This study is not yet open for participant recruitment.
See Contacts and Locations
Verified November 2016 by French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
Sponsor:
Collaborators:
European Commission
Swiss Government
Medical Research Council
FIT Biotech Ltd.
Fred Hutchinson Cancer Research Center
University College, London
Centre Hospitalier Universitaire Vaudois
Imperial College London
Istituto Nazionale Malattie Infettive Lazaro Spallanzani
Universitätsklinikum Hamburg-Eppendorf
Institut d'Investigacions Biomèdiques August Pi i Sunyer
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:
NCT02972450
First received: November 10, 2016
Last updated: November 21, 2016
Last verified: November 2016
  Purpose
EVHA T01 is a Phase IIb randomised therapeutic HIV vaccine trial in individuals who started antiretrovirals during primary or chronic infection. HIV+ participants will be randomised to receive active vaccine or placebo.

Condition Intervention Phase
Hiv Biological: GTU-MultiHIV B-clade vaccine Biological: MVA HIV-B HIV vaccine Biological: Placebo 1: Sodium Chloride Biological: Placebo 2:S08 buffer Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Phase IIb Randomised Therapeutic HIV Vaccine Trial in Individuals Who Started Antiretrovirals During Primary or Chronic Infection

Resource links provided by NLM:


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:
  • 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 Frame: 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. ]

Secondary Outcome Measures:
  • Grade 3 and worse solicited clinical and laboratory adverse events [ Time Frame: From randomisation to study completion, about 60 weeks. ]
  • Any event leading to interruption in the vaccine schedule [ Time Frame: From randomisation to study completion, about 60 weeks. ]
  • Any event that results in resuming treatment during the ATI [ Time Frame: From randomisation to study completion, about 60 weeks. ]
  • Serious Adverse Events [ Time Frame: From randomisation to 30 days after the last protocol visit ]
  • Other clinical and laboratory adverse events [ Time Frame: From randomisation to study completion, about 60 weeks. ]
  • Time to VL suppression after restarting ART [ Time Frame: From randomisation to VL suppression after restarting ART ]

Other Outcome Measures:
  • HIV-specific CD4 and CD8 responses induced by vaccination, measured using flow cytometry [ Time Frame: Week 0 and week 14 ]
  • Cytokine profile of HIV-specific CD4 and CD8 responses measured using flow cytometry [ Time Frame: Week 0 and week 14 ]
  • Number of innate immune responses measured using flow cytometry and Luminex assays [ Time Frame: On the day of the first vaccination prior to the vaccination and day 1 post all vaccinations ]
  • Viral inhibition [ Time Frame: Week 0 and week 14 ]

Estimated Enrollment: 170
Study Start Date: February 2017
Estimated Study Completion Date: July 2018
Estimated Primary Completion Date: July 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Primary Infection; Active vaccine

DNA: 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.

MVA: 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 Biological: MVA HIV-B HIV vaccine
Placebo Comparator: Primary Infection; Placebo vaccine

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.

Biological: Placebo 1: Sodium Chloride Biological: Placebo 2:S08 buffer
Experimental: Chronic Infection: Active vaccine

DNA: 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.

MVA: 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 Biological: MVA HIV-B HIV vaccine
Placebo Comparator: Chronic Infection: Placebo vaccine

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.

Biological: Placebo 1: Sodium Chloride Biological: Placebo 2:S08 buffer

Detailed Description:
EVHA T01 is an international, multicentre, double-blind study which will be a two-arm prospective 1:1 randomisation comparing active vaccines with placebo control. Randomisation will be stratified according to the stage of infection when antiretroviral therapy (cART) was commenced either during primary infection or chronic infection. Screening will take place during the 6 weeks prior to randomisation. Eligible participants will be enrolled at week 0 and randomised to either vaccine or placebo. They will continue on cART during the 12 week vaccination period and for 12 weeks beyond. Treatment will then be interrupted and resumed when the viral load rebounds to 10,000 or more copies/ml, or the CD4 falls to 350 or less cells/mm3, or there is evidence of disease progression, or they have completed 24 weeks interruption.
  Eligibility

Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Aged 18 - 65 years old
  2. Weight >50kg
  3. Able to give written informed consent including consent to long-term follow-up
  4. Nadir CD4 count > 300 cells/mm3
  5. CD4 count at screening > 600 cells/mm3
  6. Started cART after 2009 and on cART for at least one year.
  7. Viral load less than 50 copies/ml at screening.
  8. Willing to interrupt cART for up to 24weeks
  9. 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)
  10. If heterosexually active female able to have children, using 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 14 days prior to the first vaccination until 4 months after the last, and willing to undergo urine pregnancy tests prior to each vaccination
  11. If heterosexually active male able to have children, using an effective method of contraception with their partner from the first day of vaccination until 4 months after the last vaccination
  12. Willing to avoid all other vaccines within 4 weeks of scheduled study vaccines
  13. Willing and able to comply with visit schedule and provide blood sampling
  14. Participants with medical insurance or in National Healthcare System

Exclusion Criteria:

  1. Pregnant or lactating
  2. HIV-2 infection (either isolated or associated with HIV-1)
  3. VL >200 copies/ml on 2 occasions in the 12 months prior to screening
  4. Previous interruptions in cART
  5. Previous virological failures defined by loss of virological suppression with the presence of resistant mutations
  6. Haemoglobin (Hb<12g/dL for males, <11g/dL for females)
  7. Concomitant or previous conditions that preclude vaccination.
  8. History of experimental vaccinations against HIV
  9. Previous treatment with chemotherapy (except for chemotherapy injected into skin lesions for Kaposi's Sarcoma)
  10. Treatment with systemic corticoids or immuno-suppressive agents ongoing or in the previous 12 weeks before randomisation in the trial
  11. Administration of an inactivated vaccine within 30 days or a live vaccine within 60 days prior to randomisation
  12. Presence of a skin condition or marking that precludes inspection of the administration site
  13. History of cancer (except basal cellular skin carcinoma or Kaposi's sarcoma)
  14. History of cardiovascular disease (angina, myocardial infarction, transient ischemic attack, stroke); participants with controlled blood pressure are eligible.
  15. History of clinical autoimmune disease or reactive arthritis
  16. Ongoing cardiac, pulmonary (excluding mild asthma), thyroid, renal or neurological (peripheral or central) diseases
  17. Participating in another biomedical research study within 30 days of randomisation.
  18. Known hypersensitivity to any component of the vaccine formulations used in this trial including aminoglycosides and eggs or have severe or multiple allergies to drugs or pharmaceutical agents.
  19. Liver disease including hepatitis B (surface antigen positive) or hepatitis C (antigen or PCR positive)
  20. A clinically significant abnormality on ECG
  21. 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
  22. Grade 2 or worse routine laboratory parameters (see Appendix 4 for definitions). Hyperbilirubinaemia to be considered an exclusion criterion only when confirmed to be conjugated bilirubinaemia
  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: NCT02972450

Contacts
Contact: Sue L Fleck, PhD s.fleck@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)
European Commission
Swiss Government
Medical Research Council
FIT Biotech Ltd.
Fred Hutchinson Cancer Research Center
University College, London
Centre Hospitalier Universitaire Vaudois
Imperial College London
Istituto Nazionale Malattie Infettive Lazaro Spallanzani
Universitätsklinikum Hamburg-Eppendorf
Institut d'Investigacions Biomèdiques August Pi i Sunyer
Investigators
Study Director: Yves Levy, MD Institut National de la Santé Et de la Recherche Médicale, France
  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: NCT02972450     History of Changes
Other Study ID Numbers: EHVA T01/ANRS VRI05
Study First Received: November 10, 2016
Last Updated: November 21, 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Additional relevant MeSH terms:
Vaccines
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 25, 2017