Chidamide in Combination With ART for Reactivation of the Latent HIV-1 Reservoir

NCT02902185 | Unknown Phase 2 DMC

• 1 other identifier: 2016TD-Chidamide RCT
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 3

Brief 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. This study is subsequent to our NCT02513901. The purpose of this study is to verify the efficacy of multi-dose Chidamide in combination with antiretroviral therapy in HIV-infected adults with suppressed viral load in a randomized controlled clinical trial.

Conditions

Chronic HIV Infections

Keywords

Chidamide; Histone Deacetylase Inhibitor; HIV-1 Reservoir; Chronic HIV infections; HIV Eradication; Antiretroviral Therapy

Outcome Measures

Primary Outcomes (3)

• Change in HIV transcription measured as cell associated HIV-1 RNA (copies per 10E6 PBMCs)

  Measured on week 0, 2, 4, 8, 12, 14, 16, 24

• Change in HIV production measured as plasma HIV RNA (by Roche COMBAS TaqMan HIV-1 Test version 2.0)

  Measured on week 0, 2, 4, 8, 12, 14, 16, 24, 36, 48, 60, 72, 84, 96

• Change in HIV-1 reservoir size measured in PBMCs by Total HIV-1 DNA(copies per 10E6 PBMCs)

  Measured on week 0, 2, 4, 8, 12, 14, 16, 24, 36, 48, 60, 72, 84, 96

Secondary Outcomes (3)

• 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)

  Measured through 96 weeks

• Cell surface markers of immune activation and immune checkpoints and so on

  Measured on week 0, 2, 4, 8, 12, 14, 16, 24, 36, 48, 60, 72, 84, 96

• Plasma inflammatory biomarkers

  Measured on week 0, 4, 8, 12, 16, 24, 48, 72, 96

Study Arms (2)

Chidamide

EXPERIMENTAL

Chidamide will be administrated 10mg each time, twice a week, interval not less than 3 days for 12 weeks.

Drug: ART plus Chidamide

Placebo-controlled

PLACEBO COMPARATOR

Placebo with the same taste and appearance like Chidamide will be administrated 10mg each time, twice a week, interval not less than 3 days for 12 weeks.

Drug: ART plus Placebo

Interventions

ART plus Chidamide DRUG

Chidamide will be administrated 10mg each time, twice a week, interval not less than 3 days for 12 weeks.Antiretroviral therapy will be kept during entire study.

Chidamide

ART plus Placebo DRUG

Placebo will be administrated 10mg each time, twice a week, interval not less than 3 days for 12 weeks.Antiretroviral therapy will be kept during entire study.

Placebo-controlled

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Documented HIV-1 infection
• Currently receiving cART and having received cART for a minimum of 24 months, HIV-1 plasma RNA \<20 copies/mL for at least 1.5 year (excluding viral load blips)
• CD4 T cell count \>350 cells/mm3
• Able, willing to give written informed consent and to adhere to therapy and to comply with time requirements for study visits and evaluations
• Adequate vascular access for leukapheresis

You may not qualify if:

• Acute HIV-1 infection
• Received blood transfusions or hematopoetic growth factors within 3 months receipt of compounds with HDAC inhibitor-like activity, such as valproic acid within the last 1 month. Potential participants may enroll after a 30-day washout period.
• Any significant acute medical illness in the past 8 weeks
• Any evidence of an active AIDS-defining opportunistic infection
• Hepatitis B or C infection as indicated by the presence of Hepatitis B surface antigen (HBsAg) or hepatitis C virus RNA (HCV-RNA) in blood
• Patient has the following laboratory values within 3 weeks before starting the investigational drug
• Hepatic transaminases (AST or ALT) ≥3 x upper limit of normal (ULN)
• Serum total bilirubin ≥1.5 ULN
• Serum creatinine levels ≥1.5 x ULN, or calculated creatinine clearance ≤60 ml/min
• Platelet count ≤100 x109/L
• Absolute neutrophil count ≤1.5x109/L
• Serum potassium, magnesium, phosphorus outside normal limits
• Total calcium (corrected for serum albumin) or ionized calcium ≤lower normal limits
• A personal history of clinically significant cardiac disease, symptomatic or asymptomatic arrhythmias, syncopal episodes, or additional risk factors for Torsades de pointes (e.g. heart failure)
• History of malignancy or transplantation, including skin cancers or Kaposi sarcoma

Sponsors & Collaborators

• Tang-Du Hospital: lead
• Chipscreen Biosciences, Ltd.: collaborator
• Zhejiang University: collaborator
• First Affiliated Hospital of Guangxi Medical University: collaborator

Study Sites (3)

The First Affiliated Hospital of Guangxi Medical University

Nanning, Guangxi, China

Location

Department of Infectious Diseases, Tangdu Hospital, The Fourth Military Medical University

Xi'an, Shaanxi, 710038, China

Location

Zhejiang University

Hangzhou, Zhejiang, China

Location

MeSH Terms

Interventions

N-(2-amino-5-fluorobenzyl)-4-(N-(pyridine-3-acrylyl)aminomethyl)benzamide

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Department of Infectious Diseases

Study Record Dates

• First Submitted: September 6, 2016
• First Posted: September 15, 2016
• Study Start: November 29, 2016
• Primary Completion: August 1, 2018
• Study Completion: December 1, 2018
• Last Updated: April 26, 2018

Record last verified: 2018-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (3)