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

January 12, 2020 updated by: Yongtao Sun, MD, PhD, Tang-Du Hospital

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
13

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Shaanxi
      • Xi'an, Shaanxi, China, 710038
        • Department of Infectious Diseases, Tangdu Hospital, The Fourth Military Medical University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 65 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
EXPERIMENTAL: Chidamide

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
Chidamide will be given by mouth on Day 0, 3, 7, 10, 14, 17, 21, 24.
Other Names:
  • HBI-8000
  • CS055

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
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.
Measured on day 0, 1, 2, 3, 8, 11, 14, 15, 17, 21, 24, 25, 26, 27, 56.

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change in cell-associated HIV-1 RNA
Time Frame: Measured on day 0, 1, 2, 3, 11, 21, 24, 26, 56.
Measured on day 0, 1, 2, 3, 11, 21, 24, 26, 56.
Change in cell-associated total HIV-1 DNA
Time Frame: Measured on day 0, 14, 27, 56.
Measured on day 0, 14, 27, 56.
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.
Measured through 56 days after the administration of chidamide.
Change of plasma concentration of chidamide (pharmacokinetic profile)
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.
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.
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)
Time Frame: Measured through 72 hours after the first dose of chidamide; 5-30 minutes before chidamide administration on day 14, 17, 21.
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.
Measured through 72 hours after the first dose of chidamide; 5-30 minutes before chidamide administration on day 14, 17, 21.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Tang-Du Hospital

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Chipscreen Biosciences, Ltd.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
August 1, 2015

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
February 1, 2016

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
February 1, 2016

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 30, 2015

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 30, 2015

First Posted (ESTIMATE)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 3, 2015

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
January 18, 2020

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 12, 2020

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 2015TD-Chidamide

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