NCT02513901

Chidamide in Combination With Antiretroviral Therapy for Eradication of the Latent HIV-1 Reservoir

Safety and Efficacy of the Histone Deacetylase Inhibitor Chidamide in Combination With Antiretroviral Therapy for Eradication of the Latent HIV-1 Reservoir(CHARTER)

• Status: Completed
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 13 (actual)
• Sponsor: Tang-Du Hospital · Academic / Other
• Sex: All
• Age: 18 Years – 65 Years
• Healthy volunteers: Not accepted

Summary

HIV replication can be effectively suppressed and acquired immunodeficiency syndrome(AIDS) can be prevented with highly active antiretroviral therapy (HAART). However, HIV-infected people must remain on treatment continuously to avoid viral rebound and progression to AIDS. HIV persistence is thought to stem primarily from the presence of integrated copies of the proviral genome within long-lived cells. Because active viral gene expression causes cell death due to viral cytopathic effects and the immune response, long-lived cells likely harbor transcriptionally silent, latent provirus. HIV-1 persistence in long-lived cellular reservoirs remains a major barrier to a cure. 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 and antiretrovirals(ARVs) will be able to attack and eliminate ("Kill") the infected cells. The purpose of this study is to evaluate the safety and efficacy of multi-dose Chidamide in combination with antiretroviral therapy in HIV-infected adults with suppressed viral load.

Detailed description

Every participant will receive oral Chidamide on Day 0, 3, 7, 10, 14, 17, 21, 24. In Step 1, the dose of Chidamide will be 10 mg each time, for Step 2 30 mg each time. Participants will be enrolled into Step 1 first; if the dose given to Step 1 is well tolerated and no safety concerns are noted, Step 2 will be enrolled. All participants will keep their antiretroviral therapy during this study. Each step of this study will last for 56 days, involving 14 study visits(Screening, Day 0, 2, 3, 8, 11, 14, 15, 17, 21, 24, 26, 27, 56) for every participant. At the screening visit, participants will give a medical history and will undergo a physical exam; blood samples will be collected. Participants will undergo pharmacokinetic (PK) sampling which will require that blood be drawn at 0, 1, 2, 6, 12, 24, 48, 72h after the first dose. For multi-dose PK studies, blood samples will be collected at the same time points after the last dose. Participants will undergo pharmacodynamic (PD) sampling which will require that blood be drawn at 0, 6, 12, 24, 48, 72h after the first dose. For steady-state concentration PK and PD studies, blood samples will be collected 5-30 minutes before Chidamide administration on Day 14, 17, 21. If participants agree, their blood samples may be stored for future research.

Conditions

• Chronic HIV Infections

Interventions

Type	Name	Description
DRUG	Chidamide	Chidamide will be given by mouth on Day 0, 3, 7, 10, 14, 17, 21, 24.

Timeline

• Start date: 2015-08-01
• Primary completion: 2016-02-01
• Completion: 2016-02-01
• First posted: 2015-08-03
• Last updated: 2020-01-18

Locations

1 site across 1 country: China