A Safety and Efficacy Trial of Chidamide Combined With NKG2D CAR-NK Cell Therapy for Reducing the HIV Viral Reservoir

NCT07577986 | Not Yet Recruiting Phase 1

• 1 other identifier: HCIT-001
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

This study aims to investigate the safety and preliminary efficacy of an innovative therapeutic strategy combining chidamide with NKG2D-directed chimeric antigen receptor natural killer (CAR-NK) cells in individuals living with HIV. The approach is predicated on the "shock and kill" paradigm: chidamide is employed to reactivate latent HIV reservoirs and upregulate surface target ligands (NKG2D ligands) on infected cells; subsequently, allogeneic NKG2D CAR-NK cells are infused to specifically recognize and eliminate these "marked" cells. This is a phase I, open-label, single-arm clinical trial comprising two distinct stages: a dose-escalation phase (phase Ia, utilizing a "1+3+3" design) and a dose-expansion phase (phase Ib). A total of 20 HIV-infected individuals who are stable on antiretroviral therapy (ART) and have suppressed plasma viremia are planned for enrollment. Participants will receive oral chidamide over approximately five weeks, followed by two cycles of intravenous CAR-NK cell infusion. The primary endpoint is the safety and tolerability of the regimen, with particular attention to immune-related adverse events including cytokine release syndrome (CRS). Secondary endpoints encompass exploratory assessments of potential virologic and immunologic effects, such as alterations in plasma HIV RNA, cell-associated viral nucleic acids, and CD4+ T-cell counts. This study is intended to provide initial human safety data and preliminary evidence regarding the potential of this combination strategy to contribute toward a functional cure for HIV infection.

Conditions

HIV (Human Immunodeficiency Virus)

Keywords

HIV; CAR-NK; Functional cure

Outcome Measures

Primary Outcomes (3)

• Number of Participants with Study Drug-Related Adverse Events Grade 3 or Higher

  An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment. The investigator assesses the relationship of each event to the use of the study drug as either having a reasonable possibility or no reasonable possibility. AEs are given a grade from 1-5 with Grade 3 being severe but not life-threatening and requiring hospitalization, Grade 4 being life-threatening requiring immediate intervention and Grade 5 being death related to an AE.

  From enrollment to the end of treatment at 24 weeks

• Number of Participants with Study Drug-Related Immune-Related Adverse Events (IRAE)

  Assessed using the American Society of Clinical Oncology (ASCO) IRAE management guidelines (which utilizes the NIH CTCAE grading scale) but modified, as applicable, according to the NIH Division of AIDS (DAIDS) (v2.1) AE grading scale

  From enrollment to the end of treatment at 24 weeks

• Number of Participants with Adverse Events (AEs) Corresponding to Cytokine Release Syndrome

  Adverse Events (AEs) Corresponding to Cytokine Release Syndrome

  From enrollment to the end of treatment at 24 weeks

Secondary Outcomes (8)

• Changes in the HIV latent reservoir

  From enrollment to the end of treatment at 24 weeks

• Change in T-lymphocyte count

  From enrollment to the end of treatment at 24 weeks

• Maximum Observed Concentration (Cmax)

  From enrollment to the end of treatment at 24 weeks

• Area Under the Curve (AUCtau)

  From enrollment to the end of treatment at 24 weeks

• Time to Cmax (Tmax)

  From enrollment to the end of treatment at 24 weeks

Study Arms (1)

Chidamide Combined with NKG2D CAR-NK Cell Therapy

EXPERIMENTAL

All enrolled participants will receive oral chidamide (10 mg twice weekly) for approximately five weeks. During this period, participants will receive two cycles of intravenous infusion of allogeneic NKG2D CAR-NK cells (each cycle consisting of two consecutive daily infusions, separated by an interval of approximately two weeks). Throughout the treatment course, participants will continue their pre-existing antiretroviral regimen without modification.

Drug: Chidamide Combined with NKG2D CAR-NK Cell Therapy

Interventions

Chidamide Combined with NKG2D CAR-NK Cell Therapy DRUG

All enrolled participants will receive oral chidamide (10 mg twice weekly) for approximately five weeks. During this period, participants will receive two cycles of intravenous infusion of allogeneic NKG2D CAR-NK cells (each cycle consisting of two consecutive daily infusions, separated by an interval of approximately two weeks). Throughout the treatment course, participants will continue their pre-existing antiretroviral regimen without modification.

Chidamide Combined with NKG2D CAR-NK Cell Therapy

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• A participant will be deemed eligible for enrollment only if all of the following criteria are met:
• Diagnosis of HIV infection, with a current history of highly active antiretroviral therapy (HAART) for a minimum duration of two years.
• Age between 18 and 65 years, inclusive.
• Plasma HIV RNA level \< 50 copies/mL (virologic suppression).
• CD4⁺ T cell count \> 200 cells/μL.
• Adequate hematologic function defined as:
• Hemoglobin ≥ 90 g/L;
• Platelet count ≥ 75 × 10⁹/L;
• Absolute neutrophil count (ANC) ≥ 1.0 × 10⁹/L;
• White blood cell count ≥ 2 × 10⁹/L.
• Adequate hepatic and renal function defined as:
• Serum creatinine ≤ 1.5 × upper limit of normal (ULN);
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 × ULN;
• Total bilirubin ≤ 2 × ULN;
• Prothrombin time (PT) prolongation \< 3 seconds.

You may not qualify if:

• Participants meeting any of the following criteria will be excluded from study participation:
• Presence of severe cardiovascular, respiratory, or hematologic disease; active infectious disease (other than controlled HIV infection); or active malignancy.
• Positive serology for hepatitis B surface antigen (HBsAg) or detectable hepatitis C virus RNA (HCV RNA).
• Diagnosis of chronic kidney disease (CKD).
• History or presence of acute or chronic pancreatitis.
• Active severe peptic ulcer disease.
• Current severe neurologic or psychiatric disorder.
• History of alcohol abuse or illicit substance use disorder.
• Known allergic diathesis or hypersensitivity to any component of the investigational agents.
• Female participants who are pregnant, lactating, or of childbearing potential and unwilling to adhere to required contraceptive measures.
• Concurrent use of immunosuppressive agents.
• Any other condition that, in the opinion of the investigator, renders the participant unsuitable for study participation.

Sponsors & Collaborators

• First Affiliated Hospital of Zhejiang University: lead
• Hangzhou Suxi Biopharmaceutical Co., Ltd.: collaborator

Study Sites (1)

the first affiliated hospital of Zhejiang university school of medicine, Hangzhou, Zhejiang 310000

Hangzhou, Zhejiang, 310000, China

Location

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Central Study Contacts

Biao Zhu

CONTACT

+86 87236437; zhubiao1207@zju.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief Physician

Study Record Dates

• First Submitted: April 20, 2026
• First Posted: May 11, 2026
• Study Start: May 1, 2026
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): December 30, 2027
• Last Updated: May 11, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)