Chronic HIV InfectionsPhase 1/2CHARTERNCT02513901
Chidamide in Combination With Antiretroviral Therapy for Eradication of the Latent HIV-1 Reservoir
A Phase 1/2 study testing Chidamide in people with Chronic HIV Infections, run by Tang-Du Hospital at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Chronic HIV Infections
- What is being tested?
- Chidamide
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 1 siteChina
- Study dates
- Aug 2015to Feb 2016
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
China1 site
Department of Infectious Diseases, Tangdu Hospital, The Fourth Military Medical University
Xi'an, Shaanxi, 710038
About this study
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)
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.
Read the 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.
- Conditions
- Chronic HIV Infections
- Being tested
- Chidamide
- Keywords
- Chidamide, Histone Deacetylase Inhibitor, HIV-1 Reservoir, Chronic HIV infections, Antiretroviral Therapy, HIV Eradication
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ChidamideDrug
Also called CS055, HBI-8000
Chidamide will be given by mouth on Day 0, 3, 7, 10, 14, 17, 21, 24.
| Study group | Role | What they receive |
|---|---|---|
| Chidamide | Experimental | 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. Receives: Drug: Chidamide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in plasma HIV-1 RNA
Measured: Measured on day 0, 1, 2, 3, 8, 11, 14, 15, 17, 21, 24, 25, 26, 27, 56.
Secondary outcomes (5)
Change in cell-associated HIV-1 RNA
Measured: Measured on day 0, 1, 2, 3, 11, 21, 24, 26, 56.
Change in cell-associated total HIV-1 DNA
Measured: Measured on day 0, 14, 27, 56.
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Measured: Measured through 56 days after the administration of chidamide.
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.
Measured: 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)
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: Measured through 72 hours after the first dose of chidamide; 5-30 minutes before chidamide administration on day 14, 17, 21.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Aug 2015 (estimated)
- Study startAug 2015
- Primary completionFeb 2016
- Study completionFeb 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic HIV InfectionsStudies of the same condition, open and under way.
- More trials run by Tang-Du HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- Tang-Du Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Chipscreen Biosciences, Ltd.
- Responsible party
- Principal investigator, Yongtao Sun, MD, PhD, Tang-Du Hospital
- Investigators
- Yongtao Sun, M.D., Ph.D., Principal investigator, Department of Infectious Diseases, Tangdu Hospital, The Fourth Military Medical University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02513901
- Sponsor's protocol ID
- 2015TD-Chidamide
- Acronym
- CHARTER
- Status last verified
- Jan 2020
- First submitted
- 30 Jul 2015
- Last updated
- 18 Jan 2020
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 18 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT02513901
- Acronym / sponsor ID
- CHARTER / 2015TD-Chidamide
- Conditions
- Chronic HIV Infections
- Keywords
- Chidamide, Histone Deacetylase Inhibitor, HIV-1 Reservoir, Chronic HIV infections, Antiretroviral Therapy, HIV Eradication
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 13 participants (actual)
- Lead sponsor
- Tang-Du HospitalUniversity, hospital or other
- Collaborators
- Chipscreen Biosciences, Ltd.
- Study start
- Aug 2015
- Primary completion
- Feb 2016 (actual)
- Study completion
- Feb 2016 (actual)
- First posted
- 3 Aug 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Chidamide | Experimental | Drug: ChidamideStep 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. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (20 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ChidamideAlso: CS055, HBI-8000Chidamide will be given by mouth on Day 0, 3, 7, 10, 14, 17, 21, 24. | Drug | Chidamide |
Primary outcome
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.
5 secondary outcomes
Change in cell-associated HIV-1 RNA
Time frame: 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.
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.
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.
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.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jan 2020.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Yongtao Sun, M.D., Ph.D. principal investigator
Department of Infectious Diseases, Tangdu Hospital, The Fourth Military Medical University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Chidamide in people with Chronic HIV Infections, run by Tang-Du Hospital at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Jan 2020.