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
Sponsored by
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
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
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
No
Studies a U.S. FDA-regulated Device Product
No
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
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
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
No
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
No
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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