Clinical trial NCT04863066: Third-Generation CAR-T-cell Therapy in Individuals With HIV-1 Infection
Official title: A Phase I Trial Using Third-Generation CAR-T-cell Therapy in Individuals With HIV-1 Infection
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: HIV-1
Keywords: CAR T cells
HIV-1 infection
safety
HIV latent reservoir
Lead sponsor: Beijing 302 Hospital
Sponsor class: OTHER
Collaborators: name: Tsinghua University
First posted: 2021-04-28
Enrollment: 8
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Evaluation the safety of CAR-T-cell treatment
timeFrame: 3 months
Secondary outcomes:
measure: Assessment the potential therapeutic efficacy of CAR-T cell therapy
timeFrame: 3 months
Other outcomes:
measure: Cellular kinetics of CAR-T cells
timeFrame: 3 months
Locations:
city: Beijing
country: China
facility: 302 Hospital
Study officials:
affiliation: Beijing 302 Hospital of China
name: Fu-Sheng Wang, MD
role: PRINCIPAL_INVESTIGATOR
References:
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