Safety and Effect of The HDAC Inhibitor Panobinostat on HIV-1 Expression in Patients on Suppressive HAART — CLEAR  

HIV Infection Clinical Trial

Official title: The Safety and Efficacy of The Histone Deacetylase Inhibitor Panobinostat for Purging HIV-1 From The Latent Reservoir (CLEAR) Study

Status Completed

Clinical Trial Summary

The purpose of this study is to assess the safety and ability of panobinostat to re-activate HIV transcription in latently infected CD4+ T-cells among HIV-infected patients on stable antiretroviral therapy

Clinical Trial Description

Despite effective highly active antiretroviral treatment (HAART), HIV-infection persists and rebounds upon treatment interruption, presumably due to latently infected resting CD4+ T-cells. To achieve eradication of HIV-infection this reservoir of latently HIV-infected cells must be depleted.

Several therapeutic strategies are considered in HIV-cure related research. One approach is to exploit the ability of histone deacetylase (HDAC) inhibitors to reactivate HIV-1 expression in latently infected cells in the presence of HAART.

This is an investigator initiated single-group, non-randomized interventional phase I/II trial designed to evaluate the safety and ability of oral panobinostat to activate HIV-transcription in latently infected CD4+ T-cells of HIV-infected patients on suppressive HAART. The study will enrol 16 patients. Each subject will be used as his/her own control in a before-after design: endpoints measured after study intervention will be compared to baseline for each subject.

The main study will comprise three phases:

1. A pre-treatment screening/observation phase of 4 weeks (weeks 0-4)

2. A treatment phase of 8 weeks (weeks 4-12), where 20 mg panobinostat will be administered orally on days 1, 3, and 5 (TIW) every other week (QOW) while maintaining background HAART (co-therapy)

3. A post-treatment follow-up phase of 24 weeks (weeks 12-36) to evaluate the effect of study treatment

Study participants will be reviewed 13 times during the course of study treatment and follow-up. Blood will be drawn for HIV viral load assessments, CD4 cell counts, biochemistry, hematology and additional immunological and virological analyses. An electrocardiogram of the heart (ECG) will be taken at screening, day 10 and 24 post treatment initiation.

The safety and tolerability of panobinostat will be evaluated based on physical exams, laboratory tests and questions about any problems patients may have experienced during the study. A pre-specified schedule based will guide dose modification in case of unacceptable adverse effects. ;

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• HIV Infection
• HIV Infections

• NCT number: NCT01680094
• Study type: Interventional
• Source: University of Aarhus
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: September 2012
• Completion date: January 2014