ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03517631
Recruitment Status : Recruiting
First Posted : May 7, 2018
Last Update Posted : June 20, 2018
Sponsor:
Collaborator:
Kanglin Biotech (Hangzhou) Co. LTD
Information provided by (Responsible Party):
Hongzhou Lu, Shanghai Public Health Clinical Center

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 Type : Interventional  (Clinical Trial)
Estimated 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 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 : February 27, 2018
Estimated Primary Completion Date : July 15, 2018
Estimated Study Completion Date : January 20, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS
Drug Information available for: Busulfan

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 Name: 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 Name: Busulfex




Primary Outcome Measures :
  1. Adverse side effects [ Time Frame: 18 months ]
    Patients will be monitored for any signs of adverse effects.


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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03517631


Contacts
Contact: Hongzhou Lu, M.D., Ph.D +86-021-37990333 ext 3222 luhongzhou@fudan.edu.cn
Contact: Li Liu, M.D., Ph.D 86-021-37990333 ext 3222 liulishaphc@163.com

Locations
China, Shanghai
Shanghai Public Health Clinical Center Recruiting
Shanghai, Shanghai, China, 201508
Contact: Li Liu, Ph.D    86-021-37990333 ext 3222    liulishaphc@163.com   
Sponsors and Collaborators
Shanghai Public Health Clinical Center
Kanglin Biotech (Hangzhou) Co. LTD
Investigators
Study Director: Hongzhou Lu, Ph.D Caolang Road NO. 2901, Jinshan District, Shanghai

Responsible Party: Hongzhou Lu, professor, Shanghai Public Health Clinical Center
ClinicalTrials.gov Identifier: NCT03517631     History of Changes
Other Study ID Numbers: KL1702
First Posted: May 7, 2018    Key Record Dates
Last Update Posted: June 20, 2018
Last Verified: June 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Hongzhou Lu, Shanghai Public Health Clinical Center:
HIV
AIDS
Lentivirus
shRNA
Multiplex
Gene therapy

Additional relevant MeSH terms:
HIV Infections
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Busulfan
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Alkylating
Antineoplastic Agents
Myeloablative Agonists