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

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2016 by Yongtao Sun, MD, PhD, Tang-Du Hospital
Sponsor:
Collaborators:
Chipscreen Biosciences, Ltd.
Zhejiang University
First Affiliated Hospital of Guangxi Medical University
Information provided by (Responsible Party):
Yongtao Sun, MD, PhD, Tang-Du Hospital
ClinicalTrials.gov Identifier:
NCT02902185
First received: September 6, 2016
Last updated: September 19, 2016
Last verified: September 2016
  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. 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.

Condition Intervention Phase
Chronic HIV Infections
Drug: ART plus Chidamide
Drug: ART plus Placebo
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Change in HIV transcription measured as cell associated unspliced HIV-1 RNA (copies per 10E6 CD4+ T cells) [ Time Frame: Measured on week 0, 4, 8, 12, 16, 24, 48, 72, 96 ]
  • Change in HIV transcription measured as plasma HIV RNA (by Roche COMBAS TaqMan HIV-1 Test version 2.0) [ Time Frame: Measured through 96 weeks ]
  • Change in HIV-1 reservoir size measured in CD4+ T cells by Total HIV-1 DNA(copies per 10E6 CD4+ T cells) [ Time Frame: Measured on week 0, 4, 8, 12, 16, 24, 48, 72, 96 ]
  • Change in HIV-1 reservoir size measured in CD4+ T cells by Integrated HIV-1 DNA (copies per 10E6 CD4+ T cells) [ Time Frame: Measured on week 0, 4, 8, 12, 16, 24, 48, 72, 96 ]

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) [ Time Frame: Measured through 96 weeks ]
  • T-cell subsets absolute count [ Time Frame: Measured on week 0, 4, 8, 12, 16, 24, 48, 72, 96 ]
  • T-cell subsets phenotype [ Time Frame: Measured on week 0, 4, 8, 12, 16, 24, 48, 72, 96 ]
  • Plasma inflammatory biomarkers [ Time Frame: Measured on week 0, 4, 8, 12, 16, 24, 48, 72, 96 ]

Estimated Enrollment: 60
Study Start Date: September 2016
Estimated Study Completion Date: December 2018
Estimated Primary Completion Date: December 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Chidamide
Chidamide will be administrated 10mg each time, twice a week, interval not less than 3 days for 12 weeks.
Drug: ART plus Chidamide
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.
Placebo Comparator: Placebo-controlled
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.
Drug: ART plus Placebo
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.

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.

  Eligibility

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 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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02902185

Contacts
Contact: Yongtao Sun, M.D., Ph.D. yongtaos@hotmail.com
Contact: Jianhui Li lijianhui0403@outlook.com

Locations
China, Guangxi
The First Affiliated Hospital of Guangxi Medical University Recruiting
Nanning, Guangxi, China
Contact: Jianning Jiang, M.D.    86771-5356531      
Principal Investigator: Jianning Jiang, M.D.         
China, Shaanxi
Department of Infectious Diseases, Tangdu Hospital, The Fourth Military Medical University Recruiting
Xi'an, Shaanxi, China, 710038
Contact: Yongtao Sun, M.D., Ph.D.    8629-84777960    yongtaos@hotmail.com   
Contact: Wen Kang, M.D., Ph.D.    86-13679292957    kangwenkevin@gmail.com   
Principal Investigator: Yongtao Sun, M.D., Ph.D.         
China, Zhejiang
Zhejiang University Recruiting
Hangzhou, Zhejiang, China
Contact: Biao Zhu, M.D., Ph.D.         
Principal Investigator: Biao Zhu, M.D., Ph.D.         
Sponsors and Collaborators
Tang-Du Hospital
Chipscreen Biosciences, Ltd.
Zhejiang University
First Affiliated Hospital of Guangxi Medical University
  More Information

Responsible Party: Yongtao Sun, MD, PhD, Director of Department of Infectious Diseases, Tang-Du Hospital
ClinicalTrials.gov Identifier: NCT02902185     History of Changes
Other Study ID Numbers: 2016TD-Chidamide RCT
Study First Received: September 6, 2016
Last Updated: September 19, 2016
Individual Participant Data  
Plan to Share IPD: No
Plan Description: We do not have data share plan because of participants' privacy.

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

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

ClinicalTrials.gov processed this record on May 25, 2017