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

Primary Purpose

Chronic HIV Infections

Status

Unknown status

Phase

Phase 2

Locations

China

Study Type

Interventional

Intervention

ART plus Chidamide

ART plus Placebo

About this trial

This is an interventional treatment trial for Chronic HIV Infections focused on measuring Chidamide, Histone Deacetylase Inhibitor, HIV-1 Reservoir, Chronic HIV infections, HIV Eradication, Antiretroviral Therapy

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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

Exclusion Criteria:

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
1. Hepatic transaminases (AST or ALT) ≥3 x upper limit of normal (ULN)
2. Serum total bilirubin ≥1.5 ULN
3. Serum creatinine levels ≥1.5 x ULN, or calculated creatinine clearance ≤60 ml/min
4. Platelet count ≤100 x109/L
5. Absolute neutrophil count ≤1.5x109/L
6. Serum potassium, magnesium, phosphorus outside normal limits
7. 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
History of diabetes mellitus
Known hypersensitivity to the components of chidamide or its analogues
Pregnancy or breast feeding, or expecting to father children within the projected duration of the study
Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial

Sites / Locations

The First Affiliated Hospital of Guangxi Medical University
Department of Infectious Diseases, Tangdu Hospital, The Fourth Military Medical University
Zhejiang University

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Chidamide

Placebo-controlled

Arm Description

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

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.

Outcomes

Primary Outcome Measures

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

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

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

Secondary Outcome Measures

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)

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

Plasma inflammatory biomarkers

Full Information

NCT ID

NCT02902185

First Posted

September 6, 2016

Last Updated

April 24, 2018

Sponsor

Tang-Du Hospital

Collaborators

Chipscreen Biosciences, Ltd., Zhejiang University, First Affiliated Hospital of Guangxi Medical University

1. Study Identification

Unique Protocol Identification Number

NCT02902185

Brief Title

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

Official Title

Efficacy of the Histone Deacetylase Inhibitor Chidamide in Combination With Antiretroviral Therapy for Reactivation of the Latent HIV-1 Reservoir:a Randomized Controlled Clinical Trial

Study Type

Interventional

2. Study Status

Record Verification Date

April 2018

Overall Recruitment Status

Unknown status

Study Start Date

November 29, 2016 (Actual)

Primary Completion Date

August 2018 (Anticipated)

Study Completion Date

December 2018 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Tang-Du Hospital

Collaborators

Chipscreen Biosciences, Ltd., Zhejiang University, First Affiliated Hospital of Guangxi Medical University

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

Detailed Description

Sixty participants will be recruited and stratified by their CD4 cell count(30 for <500 cells/μL and 30 for ≥500 cells/μL). Each layer was 1:1 randomly divided into Chidamide group or Placebo-controlled group.Chidamide and Placebo will be administrated 10mg each time, twice a week, interval not less than 3 days. Chidamide and Placebo intervention will last 12 consecutive weeks. All participants will keep their antiretroviral therapy during this study. This study will last for 96 weeks, involving 16 study visits(Screening, Week 0, 2, 4, 8, 12, 14, 16, 20, 24, 36, 48, 60, 72, 84, 96) for every participant. At the screening visit, participants will give a medical history and will undergo a physical exam; blood samples will be collected. If participants agree, their blood samples may be stored for future research.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Chronic HIV Infections

Keywords

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2, Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

60 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Chidamide

Arm Type

Experimental

Arm Description

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

Arm Title

Placebo-controlled

Arm Type

Placebo Comparator

Arm Description

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.

Intervention Type

Drug

Intervention Name(s)

ART plus Chidamide

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

ART plus Placebo

Intervention Description

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.

Primary Outcome Measure Information:

Title

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

Time Frame

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

Title

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

Time Frame

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

Title

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

Time Frame

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

Secondary Outcome Measure Information:

Title

Time Frame

Measured through 96 weeks

Title

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

Time Frame

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

Title

Plasma inflammatory biomarkers

Time Frame

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

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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 Exclusion Criteria: 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 History of diabetes mellitus Known hypersensitivity to the components of chidamide or its analogues Pregnancy or breast feeding, or expecting to father children within the projected duration of the study Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial

Facility Information:

Facility Name

The First Affiliated Hospital of Guangxi Medical University

City

Nanning

State/Province

Guangxi

Country

China

Facility Name

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

City

Xi'an

State/Province

Shaanxi

ZIP/Postal Code

710038

Country

China

Facility Name

Zhejiang University

City

Hangzhou

State/Province

Zhejiang

Country

China

12. IPD Sharing Statement

Plan to Share IPD

IPD Sharing Plan Description

We do not have data share plan because of participants' privacy.

Learn more about this trial

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

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