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

Sponsor

Shanghai Public Health Clinical Center (Other)

Overall Status

Unknown status

CT.gov ID

NCT03517631

Collaborator

R&D Kanglin Biotech (Other)

Enrollment

Location

Arms

34.1

Anticipated Duration (Months)

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
HIV Infections AIDS	Biological: shRNA-modified CD34+ cells Drug: Low dose busulfan preconditioning Drug: Busulfan preconditioning	Phase 1

Detailed 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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

6 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Infusion of autologous CD34+ cells transduced with shRNAs targeting CCR5 and HIV genomeInfusion of autologous CD34+ cells transduced with shRNAs targeting CCR5 and HIV genome

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Pilot Study to Evaluate Efficacy and Safety of Multiplexed shRNA-modified CD34+ Cells in HIV-infected Patients.

Actual Study Start Date :

Feb 27, 2018

Anticipated Primary Completion Date :

Dec 15, 2020

Anticipated Study Completion Date :

Dec 31, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: No busulfan preconditioning shRNA-modified CD34+ cells without busulfan preconditioning.	Biological: shRNA-modified CD34+ cells Infusion of CD34+ cells transduced with shRNAs.
Experimental: Low dose busulfan preconditioning shRNA-modified CD34+ cells, with a single dose of 1 mg/kg busulfan administered every 6 hours for 4 times as preconditioning for transplantation.	Biological: shRNA-modified CD34+ cells Infusion of CD34+ cells transduced with shRNAs. Drug: Low dose busulfan preconditioning A single dose of 1 mg/kg busulfan administered every 6 hours for 4 times as preconditioning for transplantation. Other Names: Busulfex
Experimental: High dose busulfan preconditioning shRNA-modified CD34+ cells, with a single dose of 1 mg/kg busulfan administered every 6 hours for 8 times as preconditioning for transplantation.	Biological: shRNA-modified CD34+ cells Infusion of CD34+ cells transduced with shRNAs. Drug: Busulfan preconditioning A single dose of 1 mg/kg busulfan administered every 6 hours for 8 times as preconditioning for transplantation. Other Names: Busulfex

Arm

Intervention/Treatment

Experimental: No busulfan preconditioning

shRNA-modified CD34+ cells without busulfan preconditioning.

Biological: shRNA-modified CD34+ cells

Infusion of CD34+ cells transduced with shRNAs.

Experimental: Low dose busulfan preconditioning

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

Biological: shRNA-modified CD34+ cells

Infusion of CD34+ cells transduced with shRNAs.

Drug: Low dose busulfan preconditioning

A single dose of 1 mg/kg busulfan administered every 6 hours for 4 times as preconditioning for transplantation.

Other Names:

Busulfex

Experimental: High dose busulfan preconditioning

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

Biological: shRNA-modified CD34+ cells

Infusion of CD34+ cells transduced with shRNAs.

Drug: Busulfan preconditioning

A single dose of 1 mg/kg busulfan administered every 6 hours for 8 times as preconditioning for transplantation.

Other Names:

Busulfex

Outcome Measures

Primary Outcome Measures

Adverse side effects [18 months]
Patients will be monitored for any signs of adverse effects.

Secondary Outcome Measures

Efficacy of treatment [18 months]
Evaluate the efficacy of modified autologous CD34+ cells by monitoring CD4 counts and HIV-1 RNA level.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 50 Years

Sexes Eligible for Study:

All

Accepts 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.