Chronic HIV-infection Clinical Trial
— REDUCOfficial 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
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.
| Status | Active, not recruiting |
| Enrollment | 26 |
| Est. completion date | December 2015 |
| Est. primary completion date | August 2015 |
| Accepts healthy volunteers | No |
| Gender | Both |
| Age group | 18 Years and older |
| Eligibility |
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 |
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
| Country | Name | City | State |
|---|---|---|---|
| Denmark | Aarhus University Hospital, Skejby Sygehus | Aarhus N |
| Lead Sponsor | Collaborator |
|---|---|
| Bionor Immuno AS | Celgene Corporation |
Denmark,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Primary endpoint Part A | 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) | Part A 12 weeks | Yes |
| Primary | Primary endpoint Part B | 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)) | Part B Week 41 | No |
| Primary | Primary endpoint Part B | 2.Latent reservoir size measured in CD4+ T cells by: Integrated HIV-1 DNA (copies per 106 CD4+ T cells) | Part B Week 41 | No |
| Primary | Primary endpoint Part B | 2.Latent reservoir size measured in CD4+ T cells by: Total HIV-1 DNA (copies per 106 CD4+ T cells) | Part B Week 41 | No |
| Secondary | Secondary endpoints Part A | 1) HIV transcription measured as cell associated unspliced HIV-1 RNA (copies per 106 CD4+ T cells) | Part A 12 weeks | No |
| Secondary | Secondary endpoints Part A | 2) HIV transcription measured as plasma HIV RNA (by NAT screen and standard HIV RNA) | Part A 12 weeks | No |
| Secondary | Secondary endpoints Part A | 3) Histone H3 acetylation in lymphocytes | Part A 12 weeks | No |
| Secondary | Secondary endpoints Part A | 4) Size of the latent HIV-1 reservoir as measured in CD4+ T cells as measured by HIV-1 viral outgrowth assay (HIV-1 RNA per 106 in resting memory CD4+ T cells (RUPM)) Integrated HIV-1 DNA (copies per 106 CD4+ T cells) Total HIV-1 DNA (copies per 106 CD4+ T cells) |
Part A 12 weeks | No |
| Secondary | Secondary Endpoints Part B | 1) Time to re-initiation of cART | Part B 41 weeks | No |
| Secondary | Secondary Endpoints Part B | 2) Time to detectable viremia during cessation of cART | Part B 41 weeks | No |
| Secondary | Secondary Endpoints Part B | 3) HIV transcription measured as cell associated unspliced HIV-1 RNA (copies per 106 CD4+ T cells) | Part B 41 weeks | No |
| Secondary | Secondary Endpoints Part B | 4) HIV-specific T-cell responses as measured by ELISpot, proliferation and/or intracellular cytokine staining | Part B 41 weeks | No |
| Secondary | Secondary Endpoints Part B | 5) Plasma HIV-1 viral load | Part B 41 weeks | No |
| Secondary | Secondary Endpoints Part B | 6) Histone H3 acetylation as measured in lymphocytes | Part B 41 weeks | No |
| Secondary | Secondary Endpoints Part B | 7) T cell count and phenotype | Part B 41 weeks | No |
| Secondary | Secondary Endpoints Part B | 8) Antibody titer to Vacc-4x peptides and to p24 as measured by ELISA | Part B 41 weeks | No |
| Secondary | Secondary Endponts Part B | 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) | Part B 41 weeks | Yes |