HIV-infection MedDRA version: 17.1 Level: LLT Classification code 10008919 Term: Chronic HIV infection System Organ Class: 100000004862
Conditions
Interventions
Product Name: VACC4X
Pharmaceutical Form: Powder for solution for injection
INN or Proposed INN: Vacc-10
Current Sponsor code: Vacc-10
Other descriptive name: VACC-10
Concentration unit: mg milligram(
Sponsors
Bionor Pharma ASA
Eligibility
Sex/Gender
All
Inclusion 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 =65 years) yes F.1.3.1 Number of subjects for this age range 2
Exclusion criteria
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To ensure that the chosen dose and dosing schedule of romidepsin is both safe and able to induce HIV-1 expression in latently infected CD4+ T cells, the study is planned in two parts with the following specific objectives: Part A 1. The primary objective is to evaluate the safety and tolerability of romidepsin at a reduced dosing of 5 mg/m2 in HIV- infected patients. Part B 2.The primary objective is to measure the effect of treatment with Vacc-4x + rhuGM-CSF and cyclic romidepsin treatment on the HIV-1 latent reservoir in HIV-infected patients virologically suppressed on cART. The main hypothesis is that therapeutic use of a potent HDACi will lead to short-term increases in HIV-1 transcription and long-term reductions in the HIV-1 reservoir size due to increased levels and responsiveness of HIV-1-specific cytotoxic T lymphocytes in Vacc-4x immunized subjects. ;Secondary Objective: PartA 1. The secondary objective is to determine the effect of romidepsin treatment on HIV-1 transcription in HIV-infected patients virologically suppressed on cART. Part B secondary objectives: - to evaluate the safety and tolerability of romidepsin and vacc4x in combination with GM-CSF -to evaluate the treatment induced effect on virological control of HIV-infection following a monitoring antiretroviral pause. - to determine the effect of Vacc-4x and romidepsin treatment on HIV-1 transcription in HIV-infected patients virologically suppressed on cART. ;Primary end point(s): Primary Endpoints PART A 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 Endpoints PART B Latent reservoir size measured in CD4+ T cells by: a) HIV-1 viral outgrowth assay (HIV-1 RNA per 106 in resting memory CD4+ T cells (RUPM)) b) Integrated HIV-1 DNA (copies per 106 CD4+ T cells) c) Total HIV-1 DNA (copies per 106 CD4+ T cells);Timep | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary Endpoints PART A 1) HIV transcription measured as cell associated unspliced HIV-1 RNA (copies per 106 CD4+ T cells) 2) HIV transcription measured as plasma HIV RNA (by NAT screen and standard HIV RNA) 3) Histone H3 acetylation in lymphocytes 4) Size of the latent HIV-1 reservoir as measured in CD4+ T cells as measured by a) HIV-1 viral outgrowth assay (HIV-1 RNA per 106 in resting memory CD4+ T cells (RUPM)) b) Integrated HIV-1 DNA (copies per 106 CD4+ T cells) c) Total HIV-1 DNA (copies per 106 CD4+ T cells) Secondary Endpoints PART B 1) Safety: Safety and tolerability evaluation as measured by adverse events (AE), adverse reactions (AR), serious adverse events (SAE), serious adverse reactions (SAR), suspected unexpected serious adverse reactions (SUSAR) and dose-limiting toxicity 2) Time to re-initiation of cART 3) Time to detectable viremia (>50copies/mL) during cessation of cART 4) HIV transcription measured as cell associated unspliced HIV-1 RNA (copies per 106 CD4+ T cells) 5) HIV-specific T-cell responses as measured by ELISpot, T cell proliferation and probably also intracellular cytokine staining 6) Plasma HIV-1 viral load 7) Histone H3 acetylation as measured in lymphocytes 8) T cell count and phenotype 9) Antibody titer to Vacc-4x peptides and to p24 as measured by 10) Change in antibody titer to C5 as measured by ELISA.;Timepoint(s) of evaluation of this end point: Part A: week 16 Part B: week 45 | — |
Countries
Denmark
Contacts
Public ContactJoris Wilms
KLIFO A/S
Outcome results
None listed