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Clinical Trials

MainTitle

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

This study has been completed
Sponsor
Bionor Immuno AS

Collaborator
Celgene Corporation

Information provided by (Responsible Party)
Bionor Immuno AS
ClinicalTrials.gov Identifier
NCT02092116

First received: March 3, 2014
Last updated: January 11, 2017
Last Verified: January 2017
History of Changes
Purpose

Purpose

The REDUC 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 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 the infected cells.

Condition Intervention Phase
HIV I Infection

Drug : Romidepsin
Biological : Vacc-4x
Biological : rhuGM-CSF
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (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

Further study details as provided by Bionor Immuno AS:

Primary Outcome Measures

  • Part A: Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) [ Time Frame: 3 weeks ]
    Safety and tolerability evaluation as measured by adverse events (AE) and serious adverse events (SAE).
  • Part B: Changes From Baseline in HIV-1 Reservoir (Total HIV-1DNA; Integrated HIV-1 DNA in Unfractionated CD4+ T Cells and Replication Competent Provirus. [ Time Frame: Day 161/175 ]
    Total HIV-1 DNA and integrated HIV-1 DNA were analysed by MMRM analysis (copies/10^6 CD4+ T cells). To estimate the frequency of infectious units per 10^6 resting memory CD4+ T cells a quantitative viral outgrowth assay (qVOA) was used. Blood samples were obtained at Day 0, Day 105 and Day 161.
Secondary Outcome Measures:
  • Part A: Changes From Baseline in HIV-1 Reservoir (Total HIV-1DNA; Integrated HIV-1 DNA in Unfractionated CD4+ T Cells and Replication Competent Provirus. Estimates of Change From Baseline of the Size of the Latent HIV-1 Reservoir in CD4+ Cells. [ Time Frame: Day 56/84 ]
    Total HIV-1 DNA and integrated HIV-1 DNA were analysed by MMRM analysis (copies/10^6 CD4+ T cells). To estimate the frequency of infectious units per 10^6 resting memory CD4+ T cells a quantitative viral outgrowth assay (qVOA) was used. Total HIV-1 DNA was measured at Day 84
  • Part B: Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) [ Time Frame: 287 days ]
    Safety and tolerability evaluation of romidepsin and Vacc-4x in combination with GM-CSF as measured by adverse events (AE) and serious adverse events (SAE).
  • Part B: Level of HIV-1 Transcription. [ Time Frame: Day 105, 112 and 119 ]
    At day 105, 112 and 119 patients receive romidepsin and 4 hours after each administration HIV transcription is measured as unspliced HIV-1 RNA.

Enrollment: 26
Study Start Date: March 2014
Study Completion Date: December 2015
Primary Completion Date: August 2015 (Final data collection date for primary outcome measure)

Arms Assigned Interventions
Other: Part A
Pre-treatment phase of 2-4 weeks (Visit 1- Visit 2a) followed by viral reactivation phase of 3 weeks (Visit 2 to Visit 7) consisting of one cycle of romidepsin infusions at a dosing of 5 mg/m2 on days 0, 7, and 14. Post-activation phase of ~9 weeks (Visit 8 to Visit 11) to assess the effect of romidepsin on the size of latent HIV-1 reservoir.
Drug: Romidepsin

Latency reversing agent

Other Name: Istodax®
Other: Part B
Pre-treatment phase of 2-4 weeks (Visit 1-Visit 2) followed by a therapeutic HIV-1 immunization phase of 12 weeks (Visit 2 to Visit 7) in which 1.2 mg Vacc-4x was administered together with 0.06 mg rhuGM-CSF at Visits 2, 3, 4, 5, 6 and 7 follow by a follow-up period of 2 weeks (Visit 8). A viral reactivation phase of 3 weeks (Visit 9-Visit 11) consisting of one cycle of 3 romidepsin infusions (5 mg/m2) followed by a post-treatment observation phase of ~9 weeks (Visit 12-Visit 13) to assess the effect of the investigational treatment on the size of the latent HIV-1 reservoir. A monitored antiretroviral pause of up to 16 weeks (Visit 14-Visit 33).
Drug: Romidepsin

Latency reversing agent

Other Name: Istodax®
Biological: Vacc-4x

Vacc-4x is a peptide-based HIV immunotherapy administered intradermally. Vacc-4x peptides are reconstituted in sterile water.

Other Name: A combination of Vacc-10, Vacc-11, Vacc-12 and Vacc-13
Biological: rhuGM-CSF

Granulocyte macrophage colony stimulating factor as a local adjuvant

Other Name: Leukine®

Detailed Description:

The study is divide into two parts. In Part A the safety and tolerability of romidepsin will be evaluated and the effect of romidepsin treatment on HIV-1 transcription in HIV-infected patients virologically suppressed on cART will be determined.
In Part B the effect of treatment with Vacc-4x + rhuGM-CSF and romidepsin treatment on the HIV-1 latent reservoir in HIV-infected patients virologically suppressed on cART will be measured.
Six patients will be enrolled for part A and the safety and tolerability profile evaluated before enrolling 20 patients in B.

Eligibility

Eligibility

Ages Eligible for Study: 18 Years and older  
Sexes Eligible for Study: All  
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

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
Aarhus N, Denmark, 8200

Sponsors and Collaborators

Bionor Immuno AS
Celgene Corporation

Investigators

Principal Investigator: Lars Jørgen Østergaard, MD, PhD Aarhus University Hospital
More Information

More Information


Responsible Party: Bionor Immuno AS  
ClinicalTrials.gov Identifier: NCT02092116   History of Changes  
Other Study ID Numbers: BPC01-001  
  2013-004747-23  
Study First Received: March 3, 2014  
Last Updated: January 11, 2017  
Individual Participant Data    
Plan to Share IPD: No  

Additional relevant MeSH terms:
Romidepsin

ClinicalTrials.gov processed this data on October 20, 2017
This information is provided by ClinicalTrials.gov.