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

Phase 1

• Conditions: HIV-1
• Interventions: Biological: CAR-T cells

• Registration Number: NCT04863066
• Lead Sponsor: 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.

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.

Study Timeline

• Status Verified: 2020-10
• Study First Submitted: 2020-12-07
• Study First Submitted QC: 2021-04-25
• Last Update Submitted: 2021-04-25
• Study First Posted: 2021-04-28
• Last Update Posted: 2021-04-28
• Study Start: 2021-05-01
• Primary Completion: 2022-06-15
• Study Completion: 2022-10-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 8

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
CAR-T-cell therapy	CAR-T cells	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.

Primary Outcome Measures

Name	Time	Method
Evaluation the safety of CAR-T-cell treatment	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

Name	Time	Method
Assessment the potential therapeutic efficacy of CAR-T cell therapy	3 months	To evaluate the change of HIV-1 latent reservoir in peripheral blood after CAR-T-cell therapy by RT-PCR

Trial Locations

Locations (1)

302 Hospital; 🇨🇳 Beijing, China