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Third-Generation CAR-T-cell Therapy in Individuals With HIV-1 Infection (TCTIWHI)

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT04863066
Recruitment Status : Not yet recruiting
First Posted : April 28, 2021
Last Update Posted : April 28, 2021
Tsinghua University
Information provided by (Responsible Party):
Beijing 302 Hospital

Brief Summary:
To evaluate the safety of autologous CAR-T-cell therapy in individuals lived with HIV-1 infection, CAR T cells are infused after ex vivo expansion and transduction with lentiviral vectors encoding a broadly neutralizing HIV-1 scFv antibody.

Condition or disease Intervention/treatment Phase
HIV-1 Biological: CAR-T cells Phase 1

Detailed Description:
This study is a prospective, single-center, single-arm, open-label and phase I clinical trial. Subjects with CD4+T cell counts greater than 350/μl and viral loads of <50 copies/ml over 1 year by antiviral treatment are enrolled. T cells are stimulated with CD3 and CD28, transduced with lentiviral vectors encoding a broadly neutralizing HIV-1 scFv antibody and expanded for approximately 2 weeks. Then, patients are infused with CAR T cells at a dosage of 1×10^5 CAR-T cells/kg body weight. If this dose is well tolerated, dosing will be increased to 5×10^5 CAR T cells/kg body weight. After infusion, adverse events, and HIV-1 latent reservoir size and CAR levels in peripheral blood will be monitored to assess the safety of CAR-T-cell treatment, potential therapeutic efficacy and kinetics of CAR T cells.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 8 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I Trial Using Third-Generation CAR-T-cell Therapy in Individuals With HIV-1 Infection
Estimated Study Start Date : May 1, 2021
Estimated Primary Completion Date : June 15, 2022
Estimated Study Completion Date : October 1, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Arm Intervention/treatment
Experimental: CAR-T-cell therapy
Four patients with plasma HIV RNA <50 copies/ml and CD4+T cell count more than 350 cells/μl receiving at least one-year antiviral treatment are injected intravenously with 1×10^5 CAR-T cells/kg body weight. If the dosage of 1×10^5 CAR-T cells/kg body weight is well tolerated, 5×10^5 CAR-T cells/kg body weight will be infused for another 4 subjects who meet the inclusion and exclusion criteria.
Biological: CAR-T cells
The presence of latent infected cells remains a key barrier to HIV-1 functional cure. Current approach to reducing the latent HIV reservoir is to reactivate virus-containing cells to make them be detected and eliminated by host defense. Endogenous cytotoxic T-lymphocytes (CTL) may not be adequate because of cellular exhaustion and immune escape of virus. We have designed a kind of CAR-T cell based on CTL engineered to express a scFv of a broadly neutralizing anti-HIV antibody. According to our preclinical studies, CAR-T cells strongly eradicated HIV-1-infected target cells making them a particularly suitable candidate to reach a functional HIV cure. In this clinical trial, we mainly intend to evaluate the safety of CAR-T-Cell therapy on HIV patients whose plasma HIV has been successfully suppressed after antiviral therapy.
Other Name: HIV-1 specific chimeric antigen receptor T cells

Primary Outcome Measures :
  1. Evaluation the safety of CAR-T-cell treatment [ Time Frame: 3 months ]
    To assess the adverse events of CAR-T-cell therapy in HIV-1 infected individuals by measuring liver function, blood routine, and cytokine and so on in this clinical trial

Secondary Outcome Measures :
  1. Assessment the potential therapeutic efficacy of CAR-T cell therapy [ Time Frame: 3 months ]
    To evaluate the change of HIV-1 latent reservoir in peripheral blood after CAR-T-cell therapy by RT-PCR

Other Outcome Measures:
  1. Cellular kinetics of CAR-T cells [ Time Frame: 3 months ]
    To measure the cellular kinetics of CAR-T cells after infusion by RT-PCR and flow cytometry

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Aged 18 to 70 years
  2. HIV-1 infection by confirmed test;
  3. Receiving antiviral treatment ≥ 1 years;
  4. Current CD4+ T cell count > 350 cells/μl;
  5. HIV-1 RNA levels of < 50 copies/ml for at least a year;
  6. Patients who agrees to use two effective methods of contraception to avoid pregnancy during the study period.
  7. Patients who sign the informed consent form prior to inclusion in the study.

Exclusion Criteria:

  1. Patients with concomitant HAV, HBV, HCV, HDV, HEV, EBV, CMV or syphilis infection;
  2. A history of AIDS-related opportunistic infections and tumors within 1 year prior to enrollment;
  3. A History of corticosteroids or immunosuppressive drugs for autoimmune diseases by physicians within the last 2 years;
  4. Participants with clinically significant laboratory abnormalities as follows:

    • Hemoglobin ≤ 10 gm/dl (female), <11g/dl (male)
    • Absolute neutrophil count ≤ 1×10^9/L
    • Platelet count ≤100×10^9/L
    • Alanine aminotransferase (ALT)≥ 2.5 x ULN
    • Aspartate aminotransferase (AST) ≥ 2.5 x ULN
    • Total bilirubin > 1.5 ULN
    • Serum creatinine >110 μmol/L
    • International normalized ratio (INR) >1.5 or activated partial thromboplastin time (APTT) >45 s
  5. Patients with severe psychiatric illness, drugs or alcohol abuse;
  6. A woman who is in pregnancy or lactation;
  7. A history of central nervous system disease, such as cerebral hemorrhage, dementia, epilepsy and autoimmune diseases;
  8. Patients with a non-AIDS-related serious underlying disease;
  9. Patients who participate in another clinical study currently which may affect the results of this study.

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 identifier (NCT number): NCT04863066

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Contact: Jinfang Zhao, MD 010-93332866
Contact: Xuanling Shi, MD

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302 Hospital
Beijing, China, 100039
Sponsors and Collaborators
Beijing 302 Hospital
Tsinghua University
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Principal Investigator: Fu-Sheng Wang, MD Beijing 302 Hospital of China
Publications of Results:
Other Publications:

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Responsible Party: Beijing 302 Hospital Identifier: NCT04863066    
Other Study ID Numbers: 2020-HIV-001
First Posted: April 28, 2021    Key Record Dates
Last Update Posted: April 28, 2021
Last Verified: October 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Beijing 302 Hospital:
CAR T cells
HIV-1 infection
HIV latent reservoir
Additional relevant MeSH terms:
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