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

Primary Purpose

Chronic HIV Infections

Status

Completed

Phase

Phase 1

Locations

China

Study Type

Interventional

Intervention

Chidamide

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, Antiretroviral Therapy, HIV Eradication

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 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

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

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

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Chidamide

Arm Description

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.

Outcomes

Primary Outcome Measures

Change in plasma HIV-1 RNA

Secondary Outcome Measures

Change in cell-associated HIV-1 RNA

Change in cell-associated total HIV-1 DNA

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

Change of plasma concentration of chidamide (pharmacokinetic profile)

Participants will undergo pharmacokinetic sampling which will require that blood be drawn at 0, 1, 2, 6, 12, 24, 48, 72h after the first and last dose of chidamide and 5-30 minutes before chidamide administration on day 14, 17, 21.

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

Participants will undergo pharmacodynamic sampling which will require that blood be drawn at 0, 6, 12, 24, 48, 72h after the first dose of chidamide and 5-30 minutes before chidamide administration on day 14, 17, 21.

Full Information

NCT ID

NCT02513901

First Posted

July 30, 2015

Last Updated

January 12, 2020

Sponsor

Tang-Du Hospital

Collaborators

Chipscreen Biosciences, Ltd.

1. Study Identification

Unique Protocol Identification Number

NCT02513901

Brief Title

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

Acronym

CHARTER

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

January 2020

Overall Recruitment Status

Completed

Study Start Date

August 2015 (undefined)

Primary Completion Date

February 2016 (Actual)

Study Completion Date

February 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Tang-Du Hospital

Collaborators

Chipscreen Biosciences, Ltd.

4. Oversight

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. 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.

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, Antiretroviral Therapy, HIV Eradication

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

13 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Chidamide

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Chidamide

Other Intervention Name(s)

CS055, HBI-8000

Intervention Description

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

Primary Outcome Measure Information:

Title

Change in plasma HIV-1 RNA

Time Frame

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

Secondary Outcome Measure Information:

Title

Change in cell-associated HIV-1 RNA

Time Frame

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

Title

Change in cell-associated total HIV-1 DNA

Time Frame

Measured on day 0, 14, 27, 56.

Title

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

Time Frame

Measured through 56 days after the administration of chidamide.

Title

Change of plasma concentration of chidamide (pharmacokinetic profile)

Description

Time Frame

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

Title

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

Description

Time Frame

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

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 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 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Yongtao Sun, M.D., Ph.D.

Organizational Affiliation

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

Official's Role

Principal Investigator

Facility Information:

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

12. IPD Sharing Statement

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

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