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

Primary Purpose

HIV Infections, AIDS

Status
Unknown status
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
shRNA-modified CD34+ cells
Low dose busulfan preconditioning
Busulfan preconditioning
Sponsored by
Shanghai Public Health Clinical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for HIV Infections focused on measuring HIV, AIDS, Lentivirus, shRNA, Multiplex, Gene therapy

Eligibility Criteria

18 Years - 50 Years (Adult)All SexesDoes not accept 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.

Sites / Locations

  • Shanghai Public Health Clinical CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

No busulfan preconditioning

Low dose busulfan preconditioning

High dose busulfan preconditioning

Arm Description

shRNA-modified CD34+ cells without 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.

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

Outcomes

Primary Outcome Measures

Adverse side effects
Patients will be monitored for any signs of adverse effects.

Secondary Outcome Measures

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

Full Information

First Posted
March 20, 2018
Last Updated
February 18, 2020
Sponsor
Shanghai Public Health Clinical Center
Collaborators
R&D Kanglin Biotech
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1. Study Identification

Unique Protocol Identification Number
NCT03517631
Brief Title
An Efficacy and Safety Study of shRNA-modified CD34+ Cells in HIV-infected Patients.
Official Title
A Pilot Study to Evaluate Efficacy and Safety of Multiplexed shRNA-modified CD34+ Cells in HIV-infected Patients.
Study Type
Interventional

2. Study Status

Record Verification Date
February 2020
Overall Recruitment Status
Unknown status
Study Start Date
February 27, 2018 (Actual)
Primary Completion Date
December 15, 2020 (Anticipated)
Study Completion Date
December 31, 2020 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Shanghai Public Health Clinical Center
Collaborators
R&D Kanglin Biotech

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV Infections, AIDS
Keywords
HIV, AIDS, Lentivirus, shRNA, Multiplex, Gene therapy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Model Description
Infusion of autologous CD34+ cells transduced with shRNAs targeting CCR5 and HIV genome
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
6 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
No busulfan preconditioning
Arm Type
Experimental
Arm Description
shRNA-modified CD34+ cells without busulfan preconditioning.
Arm Title
Low dose busulfan preconditioning
Arm Type
Experimental
Arm 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.
Arm Title
High dose busulfan preconditioning
Arm Type
Experimental
Arm 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.
Intervention Type
Biological
Intervention Name(s)
shRNA-modified CD34+ cells
Intervention Description
Infusion of CD34+ cells transduced with shRNAs.
Intervention Type
Drug
Intervention Name(s)
Low dose busulfan preconditioning
Other Intervention Name(s)
Busulfex
Intervention Description
A single dose of 1 mg/kg busulfan administered every 6 hours for 4 times as preconditioning for transplantation.
Intervention Type
Drug
Intervention Name(s)
Busulfan preconditioning
Other Intervention Name(s)
Busulfex
Intervention Description
A single dose of 1 mg/kg busulfan administered every 6 hours for 8 times as preconditioning for transplantation.
Primary Outcome Measure Information:
Title
Adverse side effects
Description
Patients will be monitored for any signs of adverse effects.
Time Frame
18 months
Secondary Outcome Measure Information:
Title
Efficacy of treatment
Description
Evaluate the efficacy of modified autologous CD34+ cells by monitoring CD4 counts and HIV-1 RNA level.
Time Frame
18 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Hongzhou Lu, M.D., Ph.D
Phone
+86-021-37990333
Ext
3222
Email
luhongzhou@fudan.edu.cn
First Name & Middle Initial & Last Name or Official Title & Degree
Li Liu, M.D., Ph.D
Phone
86-021-37990333
Ext
3222
Email
liulishaphc@163.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Hongzhou Lu, Ph.D
Organizational Affiliation
Caolang Road NO. 2901, Jinshan District, Shanghai
Official's Role
Study Director
Facility Information:
Facility Name
Shanghai Public Health Clinical Center
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
201508
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Li Liu, Ph.D
Phone
86-021-37990333
Ext
3222
Email
liulishaphc@163.com

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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