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

NCT02513901 | Completed Phase 1 DMC

• 1 other identifier: 2015TD-Chidamide
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

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. 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.

Conditions

Chronic HIV Infections

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Change in plasma HIV-1 RNA

  Measured on day 0, 1, 2, 3, 8, 11, 14, 15, 17, 21, 24, 25, 26, 27, 56.

Secondary Outcomes (5)

• Change in cell-associated HIV-1 RNA

  Measured on day 0, 1, 2, 3, 11, 21, 24, 26, 56.

• Change in cell-associated total HIV-1 DNA

  Measured on day 0, 14, 27, 56.

• Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

  Measured through 56 days after the administration of chidamide.

• Change of plasma concentration of chidamide (pharmacokinetic profile)

  Measured through 72 hours after the first and last dose of chidamide; 5-30 minutes before chidamide administration on day 14, 17, 21.

• Change of histone acetylation level in CD4+ T cells (pharmacodynamic profile)

  Measured through 72 hours after the first dose of chidamide; 5-30 minutes before chidamide administration on day 14, 17, 21.

Study Arms (1)

Chidamide

EXPERIMENTAL

Step 1 - Six participants will receive Chidamide 10 mg twice a week(BIW) for 4 consecutive weeks. Step 2 - Another six participants will receive Chidamide 30 mg twice a week(BIW) for 4 consecutive weeks. 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.

Drug: Chidamide

Interventions

Chidamide DRUG

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

Also known as: CS055, HBI-8000

Chidamide

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 18 months, HIV-1 plasma RNA \<50 copies/mL for at least 1 year (excluding viral load blips)
• CD4 cell count above 350 cells/μL
• 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)

Sponsors & Collaborators

• Tang-Du Hospital: lead
• Chipscreen Biosciences, Ltd.: collaborator

Study Sites (1)

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

Xi'an, Shaanxi, 710038, China

Location

MeSH Terms

Interventions

N-(2-amino-5-fluorobenzyl)-4-(N-(pyridine-3-acrylyl)aminomethyl)benzamide; HBI-8000

Study Officials

• Yongtao Sun, M.D., Ph.D.

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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Department of Infectious Diseases

Study Record Dates

• First Submitted: July 30, 2015
• First Posted: August 3, 2015
• Study Start: August 1, 2015
• Primary Completion: February 1, 2016
• Study Completion: February 1, 2016
• Last Updated: January 18, 2020

Record last verified: 2020-01

Locations

CN (1)