Immunogenicity and Safety of 4 Prime-boost Combinations of HIV Vaccine Candidates in Healthy Volunteers (VRI01)

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified September 2013 by French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
Sponsor:
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:
NCT02038842
First received: January 2, 2014
Last updated: January 16, 2014
Last verified: September 2013
  Purpose

The development of a safe and effective HIV-1 vaccine strategy would probably be the best solution for the ultimate control of the worldwide AIDS pandemic. Heterologous prime-boost immunisations are today considered promising HIV prophylactic vaccine strategies. It is thus relevant to pursue the development of different candidate vaccines in prime-boost vaccine strategies to identify the most promising prime-boost combinations and to integrate scientific inquiry into trial protocols from the beginning to maximize learning opportunities.


Condition Intervention Phase
HIV Infection
Biological: LIPO-5
Biological: MVA HIV-B (MVATG17401)
Biological: GTU®-MultiHIV B: 0.5 mL IM via Biojector® 2000 and 0.5mL IntraDermic, 3 shots
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Phase I/II Open-label Randomized Multicenter Trial to Assess Immunogenicity and Safety of 4 Prime-boost Combinations of HIV Vaccine Candidates (MVA HIV-B/ LIPO-5; LIPO-5/MVA HIV-B; GTU®-MultiHIV B / LIPO-5; GTU®-MultiHIV B/MVA HIV-B) in Healthy Volunteers at Low Risk of HIV 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:
  • Evaluation of the safety of MVA HIV-B at Week 2 in arm 1 [ Time Frame: Visit Week 2 ] [ Designated as safety issue: Yes ]
    • Proportion of participants without any grade 3 or 4 adverse events (clinical or biological) related to MVA-vaccine immunisation, reported from Week 0 to Week 2 in arm 1

  • To discard vaccine strategies with an insufficient level of immunogenicity, defined by HIV-specific IFN-γ-ELISPOT responses, among 4 HIV prophylactic prime-boost combinations in healthy volunteers at low risk of HIV infection [ Time Frame: Visit Week 30 ] [ Designated as safety issue: No ]
    Proportion of participants with a HIV-specific Interferon-gamma Enzyme Linked Immunosorbent SPOT (IFN-γ ELISPOT) response in each of the 4 arms, defined by a positive response to at least one of the stimulating HIV peptide pools (15-mer pools covering Env, Gag, Pol, and Nef) measured in stimulated Peripheral Blood Mononuclear Cell (PBMC) by a standard IFN-γ ELISPOT assay at Week 30, i.e. 2 weeks after the last vaccine immunisation.


Secondary Outcome Measures:
  • To assess the tolerance of each prime-boost combination [ Time Frame: visit Week 52 ] [ Designated as safety issue: Yes ]
    • Grade 1 or more clinical and laboratory adverse events related to vaccine immunisation: proportion of participants with an event; number, nature, grade and time of occurrence.
    • Any event related to vaccine immunisation, leading to discontinuation of the immunisation regimen: proportion of participants with an event; number, nature, grade and time of occurrence.
    • Grade 3 or 4 clinical and laboratory adverse events, validated by the Endpoint Review Committee, regardless of the relationship to vaccine immunisation: proportion of participants with an event; number, nature, grade and time of occurrence.
    • Serious adverse events, regardless of the relationship to vaccine immunisation: proportion of participants with an event; number, nature, grade and time of occurrence.

  • To assess for each prime-boost combination the type of vaccine-induced T cell response [ Time Frame: Visit Week 30 ] [ Designated as safety issue: No ]

    In all participants having received at least 1 dose of vaccine:

    • Proportion of HIV-specific IFN-γ-ELISPOT responders
    • Ex-vivo transcriptome analysis

    In participants having received at least 1 dose of vaccine and a positive IFN-γ-ELISPOT response at the considered timepoint:

    • Magnitude and breadth of HIV-specific IFN-γ-ELISPOT responses, measured following stimulation of PBMC with HIV-1 peptide pools 2 weeks after each vaccine immunisation.

    In a random sample of participants, having received at least 1 dose of vaccine, with random sampling stratified on trial arm and ELISPOT response at Week 30:

    • Production of cytokine (IFN- γ, Interleukin-2 (IL-2), Tumor Necrosis Factor-alfa (TNF-alfa)) by HIV-specific Cluster of Differentiation 8 (CD8+) and Cluster of Differentiation 4 (CD4+) T cells
    • Secretion of cytokines by PBMC measured by Luminex®
    • Gene expression profile of PBMC measured by transcriptome analysis


Estimated Enrollment: 92
Study Start Date: February 2014
Estimated Study Completion Date: March 2016
Estimated Primary Completion Date: August 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: MVA HIV-B and LIPO-5 vaccines
MVA HIV-B primes 0,5 milliliter (mL) Intramuscular at Week 0 and Week 8 LIPO-5 1mL Intramuscular boosts at Week 20 and Week 28
Biological: LIPO-5
LIPO-5: 1mL IntraMuscular, 2 shots;
Other Names:
  • ANRS LIPO-5 vaccine candidate
  • ANRS MVA HIV-B (MVATG17401) vaccine candidate
  • FIT Biotech GTU-MultiHIV B vaccine candidate
Biological: MVA HIV-B (MVATG17401)
MVA HIV-B (MVATG17401): 0.5mL IntraMuscular, 2 shots;
Experimental: LIPO-5 and MVA HIV-B vaccines
LIPO-5 primes 1mL intramuscular at Week 0 and Week 8 and MVA HIV-B 0,5mL intramuscular boosts at Week 20 and Week 28
Biological: LIPO-5
LIPO-5: 1mL IntraMuscular, 2 shots;
Other Names:
  • ANRS LIPO-5 vaccine candidate
  • ANRS MVA HIV-B (MVATG17401) vaccine candidate
  • FIT Biotech GTU-MultiHIV B vaccine candidate
Biological: MVA HIV-B (MVATG17401)
MVA HIV-B (MVATG17401): 0.5mL IntraMuscular, 2 shots;
Experimental: GTU-MultiHIV B and LIPO-5 vaccines
GTU-MultiHIV B 0,5mL intramuscular via Biojector 2000 and 0,5mL intradermic primes at Week 0, Week 4 and Week 12 and LIPO-5 1mL intramuscular boosts at Week 20 and Week 28
Biological: LIPO-5
LIPO-5: 1mL IntraMuscular, 2 shots;
Other Names:
  • ANRS LIPO-5 vaccine candidate
  • ANRS MVA HIV-B (MVATG17401) vaccine candidate
  • FIT Biotech GTU-MultiHIV B vaccine candidate
Biological: GTU®-MultiHIV B: 0.5 mL IM via Biojector® 2000 and 0.5mL IntraDermic, 3 shots
GTU®-MultiHIV B: 0.5 mL IM via Biojector® 2000 and 0.5mL IntraDermic, 3 shots
Experimental: GTU-MultiHIV B and MVA HIV-B vaccines
GTU-MultiHIV B 0,5mL intramuscular via Biojector 2000 and 0,5mL intradermic primes at Week 0, Week 4 and Week 12 and MVA HIV-B 0,5mL intramuscular boosts at Week 20 and Week 28
Biological: MVA HIV-B (MVATG17401)
MVA HIV-B (MVATG17401): 0.5mL IntraMuscular, 2 shots;
Biological: GTU®-MultiHIV B: 0.5 mL IM via Biojector® 2000 and 0.5mL IntraDermic, 3 shots
GTU®-MultiHIV B: 0.5 mL IM via Biojector® 2000 and 0.5mL IntraDermic, 3 shots

Detailed Description:

Phase I/II, multicenter, national, open-label, randomized trial HIV including 4 prophylactic prime-boost HIV vaccines strategies:

Volunteers are randomly allocated in a 1:1:1:1 ratio at trial entry to 4 parallel arms with the following prime-boost strategies:

Arm 1. MVA HIV-B primes at Week 0 and Week 8 + LIPO-5 boosts at Week 20 and Week 28 Arm 2. LIPO-5 primes at Week 0 and Week 8 + MVA HIV-B boosts at Week 20 and Week 28 Arm 3. GTU-MultiHIV B primes at Week 0, Week 4 and Week 12 + LIPO-5 boosts at Week 20 and Week 28 Arm 4. GTU-MultiHIV B primes at Week 0, Week 4 and Week 12 + MVA HIV-B boosts at Week 20 and Week 28

  Eligibility

Ages Eligible for Study:   21 Years to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Written and signed informed consent
  • Subject at low risk to contract HIV i.e.

    • no history of injecting drug use in the previous ten years;
    • no gonorrhea or syphilis in the last six months;
    • no high risk partner (e.g. injecting drug user, HIV positive partner) either currently or within the past six months ;
    • no unprotected anal intercourse in the last six months, outside a relationship with a regular partner known/presumed to be HIV negative ;
    • no unprotected vaginal intercourse in the last six months outside a relationship with a regular known/presumed HIV negative partner
  • Available for follow-up for the duration of the study (56 weeks from screening)
  • Willing to undergo a HIV test
  • Willing to undergo a genital infection screen
  • If heterosexually active female, using an effective method of contraception with partner (combined oral contraceptive pill; injectable contraceptive; contraceptive implant/patch; IntraUterine Contraceptive Device (IUCD); consistent record with condoms if using these; 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
  • If heterosexually active male, using an effective method of contraception with their partner from the first day of vaccination until 4 months after the last vaccination
  • Subject registered in French Health ministry computerised file and authorised to participate in a clinical trial
  • Subject covered by Health Insurance

Exclusion Criteria:

  • Clinically relevant abnormality on history or examination including history of:
  • uncontrolled infection;
  • autoimmune disease;
  • immunodeficiency or use of immunosuppressive drugs within 3 months prior to screening;
  • cancer;
  • chronic diseases requiring long-term treatment whose interruption during the trial has no impact on the health status in the short or long-term
  • Receipt of live attenuated vaccine within 60 days or other vaccine within 14 days prior to W0
  • Planned receipt of other vaccines than those planned by the protocol and those recommended in France (excluding live attenuated vaccines) during the trial follow-up (reference : Weekly Epidemiological Newsletter 14-15 dated on April 10th, 2012 (Bulletin Epidémiologique hebdomadaire 14-15 / 10 avril 2012))
  • Receipt of blood products or immunoglobin within 4 months prior to screening
  • History of severe local or general reaction to vaccination defined as
  • local: extensive, indurated redness and swelling involving most of the antero-lateral thigh or the major circumference of the arm, not resolving within 72 hours
  • general: fever ≥ 39.5°C within 48 hours; anaphylaxis; bronchospasm; laryngeal oedema; collapse; convulsions or encephalopathy within 72 hours
  • Positive for ANA antibodies at a titer considered clinically relevant by the physician (local cut-off or ≤ 1/320, whatever is lower).
  • HIV-1 or HIV-2 positive or indeterminate at screening
  • Woman expecting to conceive during the study period
  • Pregnant or breastfeeding woman
  • Grade 1 or above routine laboratory parameters
  • Known hypersensitivity to aminoglycosides and eggs (as used in the vaccine production processes)
  • Known hypersensitivity to one of the trial vaccine components, the metabolites or formulation excipients
  • Known history of smallpox vaccination
  • Anticipated non-compliance with the protocol
  • Participation in another clinical trial with an on-going exclusion period at screening
  • Participation in a HIV preventive vaccine clinical trial (unless participant were randomized in placebo arm)
  • Subject under legal guardianship or incapacitation
  • Subject who is an active blood donor and unwilling to interrupt blood donations during the his/her participation in the trial
  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: NCT02038842

Contacts
Contact: Jean-Daniel LELIEVRE, Pr +33 149812455 jean-daniel.lelievre@hmn.aphp.fr

Locations
France
Service d'Immunologie Clinique 51, avenue du Marechal de Lattre de Tassigny Not yet recruiting
Creteil, France, 94010
Contact: Jean Daniel LELIEVRE, Pr    +33149814442    jean-daniel.lelievre@hmn.aphp.fr   
Sponsors and Collaborators
French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
Investigators
Principal Investigator: Jean-Daniel LELIEVRE Study Chair, Pr Hopital Henri Mondor
Principal Investigator: Laura RICHERT Methodologist, Dr Inserm Unit 897
  More Information

No publications provided

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: NCT02038842     History of Changes
Other Study ID Numbers: 2012-002456-14
Study First Received: January 2, 2014
Last Updated: January 16, 2014
Health Authority: France: Agence Nationale de Sécurité du Médicament et des produits de santé

Additional relevant MeSH terms:
Infection
Communicable Diseases
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases

ClinicalTrials.gov processed this record on September 22, 2014