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

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ClinicalTrials.gov Identifier: NCT03619278
Recruitment Status : Not yet recruiting
First Posted : August 7, 2018
Last Update Posted : March 31, 2020
Sponsor:
Collaborators:
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

Tracking Information
First Submitted Date  ICMJE March 14, 2018
First Posted Date  ICMJE August 7, 2018
Last Update Posted Date March 31, 2020
Estimated Study Start Date  ICMJE November 1, 2020
Estimated Primary Completion Date July 15, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 6, 2018)
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
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 6, 2018)
  • 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 ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Evaluating a Combination of Immune-based Therapies to Achieve a Remission of HIV Infection
Official Title  ICMJE 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.
Brief Summary

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
  • Arm 4 (control): 14 participants 1 dose of 10-1074 antibodies and 3 doses of romidepsin
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Masking Description:
Placebo
Primary Purpose: Treatment
Condition  ICMJE HIV Infections
Intervention  ICMJE
  • Other: HIVACAR
    Participants will receive 5 vaccines of personalized RNA vaccine (HIVACAR01), 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
Study Arms  ICMJE
  • Experimental: HIVACAR
    Participants will receive 5 vaccines of personalized RNA vaccine (HIVACAR01), 2 dose of 10-1074 antibodies and 3 doses of romidepsin
    Intervention: Other: HIVACAR
  • Placebo Comparator: Placebo
    Participants will receive 5 doses of placebo, 2 doses of 10-1074 antibodies and 3 doses of romidepsin
    Intervention: Other: placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: March 27, 2020)
12
Original Estimated Enrollment  ICMJE
 (submitted: August 6, 2018)
56
Estimated Study Completion Date  ICMJE July 15, 2021
Estimated Primary Completion Date July 15, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
  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 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 60 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Felipe Garcia, MD +93.227.54.00 fgarcia@clinic.cat
Contact: Florencia Etcheverry +93.227.54.00 MFETCHEV@clinic.cat
Listed Location Countries  ICMJE Not Provided
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03619278
Other Study ID Numbers  ICMJE 2017-000566-30
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party David Garcia Cinca, Hospital Clinic of Barcelona
Study Sponsor  ICMJE David Garcia Cinca
Collaborators  ICMJE
  • IDIBAPS - Institut d'Investigacions Biomèdiques August Pi i Sunyer
  • Felipe García - Investigator Coordinator
Investigators  ICMJE Not Provided
PRS Account Hospital Clinic of Barcelona
Verification Date March 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP