An Efficacy and Safety Study of shRNA-modified CD34+ Cells in HIV-infected Patients.

Shanghai Public Health Clinical Center

Status and phase: Unknown; Phase 1

Conditions: AIDS; HIV Infections

Treatments: Drug: Busulfan preconditioning; Biological: shRNA-modified CD34+ cells; Drug: Low dose busulfan preconditioning

Study type: Interventional

Funder types: Other

Identifiers

NCT03517631

KL1702

Details and patient eligibility

About

The purpose of the study is to evaluate the efficacy and safety of autologous CD34+ cells that stably express multiplexed shRNA to treat HIV infection.

Full description

CD34+ cells will be isolated from mobilized PBMC of HIV patients. The cells will be lentivirally transduced with multiplexed shRNAs in the same vector that target CCR5 and HIV genome. Such modified cells will be infused back to the patients who have received bulsufan preconditioning before infusion. The patients will then be evaluated for efficacy and safety.

Enrollment: 6 estimated patients

Sex: All

Ages: 18 to 50 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Body mass index (BMI) from 18 - 25; body weight ≥50kg.
• Diagnosis of HIV infections/AIDS based on "Diagnostic Criteria for HIV/AIDS" WS 293-2008.
• No antiretroviral therapy (ART) in the past 6 weeks and refuse to receive ART.
• CD4 T cell count ≥350/μl.
• No plan for pregnancy in the near future and agree to practice non-drug based contraception.
• Voluntary to participate in the study, comply with the study design to complete all monitory measurements, and agree to sign the study agreement.

Exclusion criteria

• Existence of infections/opportunistic tumors.
• Mutations in the shRNA target sequences.
• White blood cell count <3x10^9/L, neutrophil count <1.5x10^9/L, hemoglobin <110g/L, platelet count <100x10^9/L.
• Liver diseases (HBV, chronic HCV infection, congenital liver metabolic disease), abnormal liver functions (test value 2x above normal).
• Kidney deficiency (Creatinine level above the upper limit of normal levels).
• Severe chronic disease, metabolic disease (e.g., diabetes), neurological and psychiatric diseases.
• History of pancreatitis.
• Women in pregnancy, lactating or at reproductive age who do not practice contraception.
• Allergy to agents or drugs used in the study.
• Verified or suspected abuse of alcohol and drugs.
• Participated in other clinical trials within 3 months.
• Based on investigator's assessment, those who are unfit for the study (e.g., general weakness, poor compliance with study design).
• Personal or family history of tumors.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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6 participants in 3 patient groups

No busulfan preconditioning

Experimental group

Description:

shRNA-modified CD34+ cells without busulfan preconditioning.

Treatment:

Biological: shRNA-modified CD34+ cells

Low dose busulfan preconditioning

Experimental group

Description:

shRNA-modified CD34+ cells, with a single dose of 1 mg/kg busulfan administered every 6 hours for 4 times as preconditioning for transplantation.

Treatment:

Biological: shRNA-modified CD34+ cells

Drug: Low dose busulfan preconditioning

High dose busulfan preconditioning

Experimental group

Description:

shRNA-modified CD34+ cells, with a single dose of 1 mg/kg busulfan administered every 6 hours for 8 times as preconditioning for transplantation.

Treatment:

Biological: shRNA-modified CD34+ cells

Drug: Busulfan preconditioning