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

NCT04863066 | Unknown Phase 1 DMC

• 1 other identifier: 2020-HIV-001
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

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.

Conditions

HIV-1

Keywords

CAR T cells; HIV-1 infection; safety; HIV latent reservoir

Outcome Measures

Primary Outcomes (1)

• Evaluation the safety of CAR-T-cell treatment

  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

  3 months

Secondary Outcomes (1)

• Assessment the potential therapeutic efficacy of CAR-T cell therapy

  3 months

Other Outcomes (1)

• Cellular kinetics of CAR-T cells

  3 months

Study Arms (1)

CAR-T-cell therapy

EXPERIMENTAL

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

Interventions

CAR-T cells BIOLOGICAL

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.

Also known as: HIV-1 specific chimeric antigen receptor T cells

CAR-T-cell therapy

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged 18 to 70 years
• HIV-1 infection by confirmed test;
• Receiving antiviral treatment ≥ 1 years;
• Current CD4+ T cell count \> 350 cells/μl;
• HIV-1 RNA levels of \< 50 copies/ml for at least a year;
• Patients who agrees to use two effective methods of contraception to avoid pregnancy during the study period.

You may not qualify if:

• Patients with concomitant HAV, HBV, HCV, HDV, HEV, EBV, CMV or syphilis infection;
• A history of AIDS-related opportunistic infections and tumors within 1 year prior to enrollment;
• A History of corticosteroids or immunosuppressive drugs for autoimmune diseases by physicians within the last 2 years;
• 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
• Patients with severe psychiatric illness, drugs or alcohol abuse;
• A woman who is in pregnancy or lactation;
• A history of central nervous system disease, such as cerebral hemorrhage, dementia, epilepsy and autoimmune diseases;

Sponsors & Collaborators

• Beijing 302 Hospital: lead
• Tsinghua University: collaborator

Study Sites (1)

302 Hospital

Beijing, 100039, China

Location

Related Publications (5)

• Walker RE, Bechtel CM, Natarajan V, Baseler M, Hege KM, Metcalf JA, Stevens R, Hazen A, Blaese RM, Chen CC, Leitman SF, Palensky J, Wittes J, Davey RT Jr, Falloon J, Polis MA, Kovacs JA, Broad DF, Levine BL, Roberts MR, Masur H, Lane HC. Long-term in vivo survival of receptor-modified syngeneic T cells in patients with human immunodeficiency virus infection. Blood. 2000 Jul 15;96(2):467-74.

  PMID: 10887107 BACKGROUND

• Mitsuyasu RT, Anton PA, Deeks SG, Scadden DT, Connick E, Downs MT, Bakker A, Roberts MR, June CH, Jalali S, Lin AA, Pennathur-Das R, Hege KM. Prolonged survival and tissue trafficking following adoptive transfer of CD4zeta gene-modified autologous CD4(+) and CD8(+) T cells in human immunodeficiency virus-infected subjects. Blood. 2000 Aug 1;96(3):785-93.

  PMID: 10910888 BACKGROUND

• Abdel-Mohsen M, Richman D, Siliciano RF, Nussenzweig MC, Howell BJ, Martinez-Picado J, Chomont N, Bar KJ, Yu XG, Lichterfeld M, Alcami J, Hazuda D, Bushman F, Siliciano JD, Betts MR, Spivak AM, Planelles V, Hahn BH, Smith DM, Ho YC, Buzon MJ, Gaebler C, Paiardini M, Li Q, Estes JD, Hope TJ, Kostman J, Mounzer K, Caskey M, Fox L, Frank I, Riley JL, Tebas P, Montaner LJ; BEAT-HIV Delaney Collaboratory to Cure HIV-1 infection. Recommendations for measuring HIV reservoir size in cure-directed clinical trials. Nat Med. 2020 Sep;26(9):1339-1350. doi: 10.1038/s41591-020-1022-1. Epub 2020 Sep 7.

  PMID: 32895573 BACKGROUND

• Liu B, Zou F, Lu L, Chen C, He D, Zhang X, Tang X, Liu C, Li L, Zhang H. Chimeric Antigen Receptor T Cells Guided by the Single-Chain Fv of a Broadly Neutralizing Antibody Specifically and Effectively Eradicate Virus Reactivated from Latency in CD4+ T Lymphocytes Isolated from HIV-1-Infected Individuals Receiving Suppressive Combined Antiretroviral Therapy. J Virol. 2016 Oct 14;90(21):9712-9724. doi: 10.1128/JVI.00852-16. Print 2016 Nov 1.

  PMID: 27535056 BACKGROUND

• Maldini CR, Claiborne DT, Okawa K, Chen T, Dopkin DL, Shan X, Power KA, Trifonova RT, Krupp K, Phelps M, Vrbanac VD, Tanno S, Bateson T, Leslie GJ, Hoxie JA, Boutwell CL, Riley JL, Allen TM. Dual CD4-based CAR T cells with distinct costimulatory domains mitigate HIV pathogenesis in vivo. Nat Med. 2020 Nov;26(11):1776-1787. doi: 10.1038/s41591-020-1039-5. Epub 2020 Aug 31.

  PMID: 32868878 RESULT

MeSH Terms

Interventions

Immunotherapy, Adoptive

Intervention Hierarchy (Ancestors)

Adoptive Transfer; Immunization, Passive; Immunization; Immunotherapy; Immunomodulation; Biological Therapy; Therapeutics; Immunologic Techniques; Investigative Techniques

Study Officials

• Fu-Sheng Wang, MD

  Beijing 302 Hospital of China

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jinfang Zhao, MD

CONTACT

010-93332866; zhaojinfang13@163.com

Xuanling Shi, MD

CONTACT

shixuanlingsk@mail.tsinghua.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: SPONSOR

Study Record Dates

• First Submitted: December 7, 2020
• First Posted: April 28, 2021
• Study Start: May 1, 2021
• Primary Completion: June 15, 2022
• Study Completion: October 1, 2022
• Last Updated: April 28, 2021

Record last verified: 2020-10

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)