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

HIV Infections Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03517631
• Other study ID #: KL1702
• Status: Recruiting
• Phase: Phase 1
• Start date: February 27, 2018
• Est. completion date: December 31, 2020

Study information

• Verified date: February 2020
• Source: Shanghai Public Health Clinical Center
• Contact: Hongzhou Lu, M.D., Ph.D
• Phone: +86-021-37990333
• Email: luhongzhou[@]fudan.edu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 6
• Est. completion date: December 31, 2020
• Est. primary completion date: December 15, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 50 Years

Eligibility

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.

Related Conditions & MeSH terms

• AIDS
• HIV Infections

Intervention

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

Locations

Country	Name	City	State
China	Shanghai Public Health Clinical Center	Shanghai	Shanghai

Sponsors (2)

Lead Sponsor	Collaborator
Shanghai Public Health Clinical Center	R&D Kanglin Biotech

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Adverse side effects	Patients will be monitored for any signs of adverse effects.	18 months
Secondary	Efficacy of treatment	Evaluate the efficacy of modified autologous CD34+ cells by monitoring CD4 counts and HIV-1 RNA level.	18 months