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

February 18, 2020 updated by: Hongzhou Lu, Shanghai Public Health Clinical Center

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

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Anticipated)

6

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • China
    • Shanghai
      • Shanghai, Shanghai, China, 201508
        • Recruiting
        • Shanghai Public Health Clinical Center
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 50 years (ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NON_RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Adverse side effects
Time Frame: 18 months
Patients will be monitored for any signs of adverse effects.
18 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Efficacy of treatment
Time Frame: 18 months
Evaluate the efficacy of modified autologous CD34+ cells by monitoring CD4 counts and HIV-1 RNA level.
18 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Shanghai Public Health Clinical Center

Collaborators

R&D Kanglin Biotech

Investigators

  • Study Director: Hongzhou Lu, Ph.D, Caolang Road NO. 2901, Jinshan District, Shanghai

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

February 27, 2018

Primary Completion (ANTICIPATED)

December 15, 2020

Study Completion (ANTICIPATED)

December 31, 2020

Study Registration Dates

First Submitted

March 20, 2018

First Submitted That Met QC Criteria

May 4, 2018

First Posted (ACTUAL)

May 7, 2018

Study Record Updates

Last Update Posted (ACTUAL)

February 19, 2020

Last Update Submitted That Met QC Criteria

February 18, 2020

Last Verified

February 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • KL1702

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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