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

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02513901
First Posted: August 3, 2015
Last Update Posted: September 7, 2016
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
Chipscreen Biosciences, Ltd.
Information provided by (Responsible Party):
Yongtao Sun, MD, PhD, Tang-Du Hospital
  Purpose
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.

Condition Intervention Phase
Chronic HIV Infections Drug: Chidamide Phase 1 Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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)

Resource links provided by NLM:


Further study details as provided by Yongtao Sun, MD, PhD, Tang-Du Hospital:

Primary 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) [ Time Frame: Measured through 56 days after the administration of Chidamide ]
    Including signs/symptoms, lab toxicities, and /or clinical events that is probably, possibly, or definitely related to study treatment

  • Pharmacokinetic (PK) profiles (area under the curve [AUC], maximum concentration [Cmax], and minimum concentration [Cmin]) for Chidamide) [ Time Frame: Measured through 72 hours after the administration of Chidamide; 5-30 minutes before Chidamide administration on Day 14, 17, 21 ]
    Participants will undergo 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. For steady-state concentration PK studies, blood samples will be collected 5-30 minutes before Chidamide administration on Day 14, 17, 21.

  • Pharmacodynamic (PD) profiles (histone acetylation in PBMC) [ Time Frame: Measured through 72 hours after the administration of Chidamide; 5-30 minutes before Chidamide administration on Day 14, 17, 21 ]
    Participants will undergo PD sampling which will require that blood be drawn at 0, 6, 12, 24, 48, 72h after the first dose. For steady-state concentration PD studies, blood samples will be collected 5-30 minutes before Chidamide administration on Day 14, 17, 21.


Secondary Outcome Measures:
  • Change in HIV-1 reservoir size measured in CD4+ T cells by Total HIV-1 DNA and Integrated HIV-1 DNA (copies per 10E6 CD4+ T cells) [ Time Frame: Measured on Day 0, 3, 14, 27, 56 ]
  • Change in HIV transcription measured as cell associated unspliced HIV-1 RNA (copies per 10E6 CD4+ T cells) [ Time Frame: Measured on Day 0, 3, 14, 27, 56 ]
  • Change in HIV transcription measured as plasma HIV RNA (by Roche COMBAS TaqMan HIV-1 Test version 2.0) [ Time Frame: Measured through 56 days ]
  • T cell count and phenotype [ Time Frame: Measured on Day 0, 27, 56 ]

Enrollment: 13
Study Start Date: August 2015
Study Completion Date: February 2016
Primary Completion Date: February 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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:
  • CS055
  • HBI-8000

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.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02513901


Locations
China, Shaanxi
Department of Infectious Diseases, Tangdu Hospital, The Fourth Military Medical University
Xi'an, Shaanxi, China, 710038
Sponsors and Collaborators
Tang-Du Hospital
Chipscreen Biosciences, Ltd.
Investigators
Principal Investigator: Yongtao Sun, M.D., Ph.D. Department of Infectious Diseases, Tangdu Hospital, The Fourth Military Medical University
  More Information

Responsible Party: Yongtao Sun, MD, PhD, Director of Department of Infectious Diseases, Tang-Du Hospital
ClinicalTrials.gov Identifier: NCT02513901     History of Changes
Other Study ID Numbers: 2015TD-Chidamide
First Submitted: July 30, 2015
First Posted: August 3, 2015
Last Update Posted: September 7, 2016
Last Verified: September 2016

Keywords provided by Yongtao Sun, MD, PhD, Tang-Du Hospital:
Chidamide
Histone Deacetylase Inhibitor
HIV-1 Reservoir
Chronic HIV infections
Antiretroviral Therapy
HIV Eradication

Additional relevant MeSH terms:
HIV Infections
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Histone Deacetylase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action