Clinical Trials

MainTitle

Evaluating a Combination of Immune-based Therapies to Achieve a Remission of HIV Infection (HIVACAR)

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

Verified March 2020 by David Garcia Cinca

Sponsor
David Garcia Cinca

Collaborator
IDIBAPS - Institut d'Investigacions Biomèdiques August Pi i Sunyer
Felipe García - Investigator Coordinator

Information provided by (Responsible Party)
David Garcia Cinca, Hospital Clinic of Barcelona

ClinicalTrials.gov Identifier
NCT03619278

First received: March 14, 2018
Last updated: March 27, 2020
Last Verified: March 2020
History of Changes
Purpose

Purpose

A phase I/IIa, multinational, multicentric (IDIBAPS, IRSICAIXA, AARHUS, VUB, APHP), randomised, balanced by centre (to include participants from the 4 arms), open-label, controlled clinical trial. Each participant will be followed up a different time according to study arm: a minimum of 38 weeks in arm I, 31 weeks in arm II, 54 weeks in arm III and 26 weeks in the arm 4. The study duration will be 104 weeks from inclusion of the first participant.

Participants will be randomised to one of the following 4 arms:

  • Arm 1 (study): 14 participants will receive 3 vaccines of HIVARNA01.3 prime, 2 MVA-vectored vaccine boosts, 1 dose of 10-1074 antibodies and 3 doses of romidepsin
  • Arm 2 (study): 14 participants will receive 5 vaccines of HIVARNA01.3, 1 dose of 10-1074 antibodies and 3 doses of romidepsin
  • Arm 3 (study): 14 participants will receive 5 vaccines of personalized RNA vaccine (HIVACAR01), 1 dose of 10-1074 antibodies and 3 doses of romidepsin
(control): 14 participants 1 dose of 10-1074 antibodies and 3 doses of romidepsin

Condition Intervention Phase
HIV Infections

Other : HIVACAR
Other : placebo
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: A Phase I/IIa, Randomised Study to Evaluate the Safety and the Effectiveness of a Combination of Therapeutic Vaccine, Broadly Neutralising Antibody (10-1074), and the Latency Reversing Agent Romidepsin to Achieve a Remission of HIV Infection in Chronically HIV-infected Participants Under Stable Combined Antiretroviral Therapy.

Further study details as provided by David Garcia Cinca, Hospital Clinic of Barcelona:

Primary Outcome Measures

  • Grade 3 or above severe local , systemic, clinical or laboratory adverse event t [ Time Frame: 12 days (28 days after each inmuisation) ]
    Local adverse events may be pain, cutaneous reactions including induration and systemic emperature, chills, headache, nausea, vomiting, malaise, and myalgia. Clinical and laboratory must be confirmed at examination or on repeat testing respectively. Any adverse event attributable to the combination therapy leading to discontinuation of the study treatmen
Secondary Outcome Measures:
  • Proportion of participants who maintain an undetectable viral load [ Time Frame: 12 weeks (after discontinuation of antiretroviral therapy) ]
    defined as a viral load below the threshold of 50 copies/ml
  • Percentage of participants with control of viral load below detectable level [ Time Frame: 24 weeks (after discontinuation of antiretroviral therapy) ]
  • Change from baseline in total proviral HIV-1 DNA per 10^6 CD4+ T cells. [ Time Frame: up to 51 weeks ]
  • Change from baseline in integrated proviral HIV-1 DNA per 10^6 CD4+ T cells. [ Time Frame: up to 51 weeks ]
  • Change from baseline in HIV-1 transcription. [ Time Frame: up to 39 weeks ]
    According to CA US HIV-1 RNA measured in unfractionated CD4+ T cells
  • Change in plasma HIV-1 RNA from baseline [ Time Frame: up to 39 weeks ]
  • Breadth and magnitude of CD4+ HIV-specific T cell responses measured by IFN-gamma ELISPOT compared with baseline. [ Time Frame: up to 27 weeks ]
  • Breadth and magnitude of CD8+ HIV-specific T cell responses measured by IFN-gamma ELISPOT compared with baseline. [ Time Frame: up to 27 weeks ]
  • Breadth and magnitude of CD4+ HIV-specific T cell responses measured by Intra-cellular cytokine staining-ICS in the study arms as compared with baseline. [ Time Frame: up to 27 weeks ]
  • Breadth and magnitude of CD8+ HIV-specific T cell responses measured by Intra-cellular cytokine staining-ICS in the study arms as compared with baseline. [ Time Frame: up to 27 weeks ]
  • Change from baseline in CD8+ T-cell HIV suppressive capacity. [ Time Frame: up to 51 weeks ]
  • Change from baseline in T cell activation markers [ Time Frame: up to 29 weeks ]
  • Change from baseline in T cell activation markers [ Time Frame: 3 weeeks ]
  • Change from baseline in T cell activation markers [ Time Frame: up to 24 weeks ]
  • Change from baseline in T cell subset distribution [ Time Frame: up to 29 weeks ]
  • Change from baseline in T cell subset distribution [ Time Frame: 14 weeks ]
  • Change from baseline in T cell subset distribution [ Time Frame: up to 27 weeks ]
  • Change from baseline in PD-1 expression [ Time Frame: up to 51 weeks ]
  • Evaluate fecal microbiome [ Time Frame: baseline and at week 14 ]
  • Characterise viral escape from vaccine-induced immune T cell responses [ Time Frame: up to 51 weeks ]
    Comparison of viral sequences pre-cART and rebounding after cART interruption
  • Analysis of changes in sensitivity to neutralisation by 10-1074 of rebounding viruses after cART interruption to identify neutralisation escape mutants. [ Time Frame: up to 51 weeks ]
  • To evaluate mRNA expression profiles in whole PBMC at baseline [ Time Frame: at first romidepsin administration and 14 and 26 weeks after first romidepsin administration ]

Estimated Enrollment: 12
Anticipated Study Start Date: November 1, 2020
Estimated Study Completion Date: July 15, 2021
Estimated Primary Completion Date: July 15, 2021 (Final data collection date for primary outcome measure)

Arms Assigned Interventions
Experimental: HIVACAR
Participants will receive 5 vaccines of personalized RNA vaccine (HIVACAR01), 2 dose of 10-1074 antibodies and 3 doses of romidepsin
Other: HIVACAR

Participants will receive 5 vaccines of personalized RNA vaccine (HIVACAR01), 2 doses of 10-1074 antibodies and 3 doses of romidepsin

Placebo Comparator: Placebo
Participants will receive 5 doses of placebo, 2 doses of 10-1074 antibodies and 3 doses of romidepsin
Other: placebo

Participants will receive 5 vaccines of placebo of HIVACAR01, 2 doses of 10-1074 antibodies and 3 doses of romidepsin

Eligibility

Eligibility

Ages Eligible for Study: 18 Years to 60 Years  
Sexes Eligible for Study: All  
Accepts Healthy Volunteers: No  

Criteria

Inclusion Criteria:

    1. Between ≥ 18 to <60 years of age
    2. Voluntarily signed informed consent
    3. Male, or female with negative pregnancy test prior to enrolment
    4. Proven HIV-1 infection (with positive antibodies against HIV-1 and a detectable plasma HIV-1 RNA before cART)
    5. Must be on stable treatment with cART for at least 18 months (cART is defined as an antiretroviral regimen consisting of at least three registered antiretroviral agents; periods of mono/dual antiretroviral therapy if not first time therapy and confirmed viral suppression during these periods of mono/dual therapy are permitted)
    6. Nadir CD4+ cell counts must be above or equal to 350 cells/µl, 2-3 occasional determinations below 350 cells/μl are allowed.
    7. Current CD4+ cell count must be at least 450 cells/µl
    8. HIV-RNA must be below 50 copies/ mL for the last 12 months prior to inclusion, during at least two measurements (occasional so called 'blips' up to 500 copies/mL are permitted)
    9. If male or female of childbearing potential willing to take correct contraceptive measures:
        1. If heterosexually active female; using an effective method of contraception from 14 days prior to the first vaccination until at least 12 weeks after the last vaccination; all female volunteers must be willing to undergo urine or serum pregnancy tests at time points specified in the Schedule of Procedures.
        2. If heterosexually active male; willing to use an effective method of contraception or agree on the use of an effective method of contraception by his partner from the day of the first vaccination until 12 weeks after the last vaccination.
      1. 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 pre-exposure prophylaxis [PrEP] for their sexual partners)


    Exclusion Criteria:
      1. Treatment with a non-cART regimen of antiretroviral agents prior to the start of any antiretroviral regimen
      2. History of a CDC class C event (see Appendix IV)
      3. Women of childbearing potential with a positive pregnancy test, or participants (male or female) who wish to plan a pregnancy during the trial period.
      4. Active opportunistic infection, or any active infection or malignancy within 30 days prior to screening visit
      5. Therapy with immunomodulatory agents, including cytokines (e.g. IL2) and gamma globulin, or cytostatic chemotherapy within 90 days prior to screening visit
      6. Use of anti-coagulant medication
      7. Use of any investigational drug during the 90 days prior to study entry
      8. Previous antiretroviral therapy failure and/or mutations conferring genotypic resistance to antiretroviral therapy
      9. Participants with severe cardiovascular diseases or long QT interval
      10. Active hepatitis C virus
      11. Hepatitis B infection
      12. Treatment with strong inhibitors or inducers of CYP3A4, except protease inhibitors for HIV treatment (see protocol section 5.7); if in treatment of protease inhibitors for HIV not willing to change inhibitor protease for an integrase inhibitor during the study.
      13. Any known allergy or intolerance to any of the study drugs or excipient
      14. Protein egg allergy
      15. Known past history of clinical Epstein-Barr Virus (EBV) infection or recurrent herpes zoster
      16. Hematologic abnormalities ≥Grade 1
      17. Potassium or magnesium levels outside the upper limit of normal (ULN) and lower limit of normal (LLN)
      18. History of autoimmune disorders as multiple sclerosis.
      19. Any other condition which, in the opinion of the investigator, may interfere with the
      evaluation of the study objectives

    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: NCT03619278

    Contacts

    Contact:   Felipe Garcia, MD +93.227.54.00 fgarcia@clinic.cat
    Contact:   Florencia Etcheverry +93.227.54.00 MFETCHEV@clinic.cat

    Sponsors and Collaborators

    David Garcia Cinca
    IDIBAPS - Institut d'Investigacions Biomèdiques August Pi i Sunyer
    Felipe García - Investigator Coordinator
    More Information

    More Information


    Responsible Party: David Garcia Cinca, Clinical Research Manager, Hospital Clinic of Barcelona  
    ClinicalTrials.gov Identifier: NCT03619278   History of Changes  
    Other Study ID Numbers: 2017-000566-30  
    Study First Received: March 14, 2018  
    Last Updated: March 27, 2020  
    Individual Participant Data    
    Plan to Share IPD: Undecided  

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

    Keywords provided by David Garcia Cinca, Hospital Clinic of Barcelona:

    HIV

    Additional relevant MeSH terms:
    Infection
    Communicable Diseases
    HIV Infections
    Acquired Immunodeficiency Syndrome

    ClinicalTrials.gov processed this data on May 29, 2020
    This information is provided by ClinicalTrials.gov.