Safety and Efficacy of the Histone Deacetylase Inhibitor Romidepsin and the Therapeutic Vaccine Vacc-4x for Reduction of the Latent HIV‐1 Reservoir (REDUC)

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by Bionor Immuno AS
Sponsor:
Collaborator:
Celgene Corporation
Information provided by (Responsible Party):
Bionor Immuno AS
ClinicalTrials.gov Identifier:
NCT02092116
First received: March 3, 2014
Last updated: March 17, 2014
Last verified: March 2014
  Purpose

The REDUC ("Kick and Kill") trial's objective is to address one of the core issues with the treatment of HIV, which is that some HIV infected cells hide in so-called latent reservoirs. The reservoirs are unaffected by conventional HIV medication and invisible to the immune system. HDACi have the potential to activate ("Kick") these latently infected cells. This will make the HIV infected cells visible to the immune system; the immune response generate by Vacc-4x will be able to attack and eliminate ("Kill") the infected cells.


Condition Intervention Phase
Chronic HIV-infection
Drug: Romidepsin (Istodax®)
Biological: Vacc-4x
Biological: rhuGM-CSF (Leukine®)
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open Phase I/IIa Study to Evaluate the Safety and Effect of Therapeutic HIV-1 Immunization Using Vacc-4x + rhuGM-CSF, and HIV-1 Reactivation Using Romidepsin, on the Viral Reservoir in Virologically Suppressed HIV-1 Infected Adults on cART

Resource links provided by NLM:


Further study details as provided by Bionor Immuno AS:

Primary Outcome Measures:
  • Primary endpoint Part A [ Time Frame: Part A 12 weeks ] [ Designated as safety issue: Yes ]
    Safety and tolerability evaluation as measured by adverse events (AE), adverse reactions (AR), serious adverse events (SAE), serious adverse reactions (SAR), serious unexpected adverse reactions (SUSAR)

  • Primary endpoint Part B [ Time Frame: Part B 41 weeks ] [ Designated as safety issue: Yes ]
    1) Safety and tolerability evaluation as measured by adverse events (AE), adverse reactions (AR), serious adverse events (SAE), serious adverse reactions (SAR), serious unexpected adverse reactions (SUSAR)

  • Primary endpoint Part B [ Time Frame: Part B Week 41 ] [ Designated as safety issue: No ]
    2.Latent reservoir size measured in CD4+ T cells by: HIV-1 viral outgrowth assay (HIV-1 RNA per 106 in resting memory CD4+ T cells (RUPM))

  • Primary endpoint Part B [ Time Frame: Part B Week 41 ] [ Designated as safety issue: No ]
    2.Latent reservoir size measured in CD4+ T cells by: Integrated HIV-1 DNA (copies per 106 CD4+ T cells)

  • Primary endpoint Part B [ Time Frame: Part B Week 41 ] [ Designated as safety issue: No ]
    2.Latent reservoir size measured in CD4+ T cells by: Total HIV-1 DNA (copies per 106 CD4+ T cells)


Secondary Outcome Measures:
  • Secondary endpoints Part A [ Time Frame: Part A 12 weeks ] [ Designated as safety issue: No ]
    1) HIV transcription measured as cell associated unspliced HIV-1 RNA (copies per 106 CD4+ T cells)

  • Secondary endpoints Part A [ Time Frame: Part A 12 weeks ] [ Designated as safety issue: No ]
    2) HIV transcription measured as plasma HIV RNA (by NAT screen and standard HIV RNA)

  • Secondary endpoints Part A [ Time Frame: Part A 12 weeks ] [ Designated as safety issue: No ]
    3) Histone H3 acetylation in lymphocytes

  • Secondary endpoints Part A [ Time Frame: Part A 12 weeks ] [ Designated as safety issue: No ]

    4) Size of the latent HIV-1 reservoir as measured in CD4+ T cells as measured by

    1. HIV-1 viral outgrowth assay (HIV-1 RNA per 106 in resting memory CD4+ T cells (RUPM))
    2. Integrated HIV-1 DNA (copies per 106 CD4+ T cells)
    3. Total HIV-1 DNA (copies per 106 CD4+ T cells)

  • Secondary Endpoints Part B [ Time Frame: Part B 41 weeks ] [ Designated as safety issue: No ]
    1) Time to re-initiation of cART

  • Secondary Endpoints Part B [ Time Frame: Part B 41 weeks ] [ Designated as safety issue: No ]
    2) Time to detectable viremia during cessation of cART

  • Secondary Endpoints Part B [ Time Frame: Part B 41 weeks ] [ Designated as safety issue: No ]
    3) HIV transcription measured as cell associated unspliced HIV-1 RNA (copies per 10⁶ CD4+ T cells)

  • Secondary Endpoints Part B [ Time Frame: Part B 41 weeks ] [ Designated as safety issue: No ]
    4) HIV-specific T-cell responses as measured by ELISpot, proliferation and/or intracellular cytokine staining

  • Secondary Endpoints Part B [ Time Frame: Part B 41 weeks ] [ Designated as safety issue: No ]
    5) Plasma HIV-1 viral load

  • Secondary Endpoints Part B [ Time Frame: Part B 41 weeks ] [ Designated as safety issue: No ]
    6) Histone H3 acetylation as measured in lymphocytes

  • Secondary Endpoints Part B [ Time Frame: Part B 41 weeks ] [ Designated as safety issue: No ]
    7) T cell count and phenotype

  • Secondary Endpoints Part B [ Time Frame: Part B 41 weeks ] [ Designated as safety issue: No ]
    8) Antibody titer to Vacc-4x peptides and to p24 as measured by ELISA


Estimated Enrollment: 26
Study Start Date: March 2014
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Part A
Part A, to confirm a safe/tolerable and efficacious dose of romidepsin in HIV patients in a small cohort (n=6)
Drug: Romidepsin (Istodax®)
Part B
Part B, to evaluate the safety/tolerability of Vacc-4x + rhuGM-CSF as adjunctive therapy to romidepsin and to assess the impact on the latent HIV reservoir and the ability to control viral load during an Analytical Treatment Interruption (n=20).
Drug: Romidepsin (Istodax®) Biological: Vacc-4x Biological: rhuGM-CSF (Leukine®)

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age >18 years
  2. Currently receiving cART and having received cART for a minimum of 1 year
  3. HIV-1 plasma RNA <50 copies/mL for at least 1 year (excluding viral load blips)
  4. CD4 T cell count ≥500 cells/mm3

Exclusion Criteria:

  1. CD4 T cell count nadir <200 cells/mm3
  2. Previous treatment with an HDACi (Histone deacetylase inhibitor) within the previous 6 months
  3. Any evidence of an active AIDS-defining opportunistic infection, active HBV or HCV co-infection, significant cardiac disease, malignancy, transplantation, insulin dependent diabetes mellitus or other protocol defined excluded medical condition
  4. Use of any protocol defined contraindicated medication or vaccination
  5. Unacceptable values of the hematologic and clinical chemistry parameters as defined in the protocol.
  6. Males or females who are unwilling or unable to use protocol defined methods of contraception
  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: NCT02092116

Locations
Denmark
Aarhus University Hospital, Skejby Sygehus Recruiting
Aarhus N, Denmark, 8200
Contact: Ole Schmeltz Søgaard, MD    +45 78 45 28 42    olesoega@rm.dk   
Principal Investigator: Lars Østergaard, MD, PhD, DMSc, Professor         
Sponsors and Collaborators
Bionor Immuno AS
Celgene Corporation
Investigators
Principal Investigator: Lars Jørgen Østergaard, MD, PhD, DMSc, Professor Aarhus University Hospital
  More Information

No publications provided

Responsible Party: Bionor Immuno AS
ClinicalTrials.gov Identifier: NCT02092116     History of Changes
Other Study ID Numbers: PBC01-001, 2013-004747-23
Study First Received: March 3, 2014
Last Updated: March 17, 2014
Health Authority: Denmark: Danish Health and Medicines Authority
United States: Food and Drug Administration

Additional relevant MeSH terms:
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
Romidepsin
Histone Deacetylase Inhibitors
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 26, 2014