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

NCT ID: NCT03517631

Last Updated: 2020-02-19

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE1

Total Enrollment

6 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-02-27

Study Completion Date

2020-12-31

Brief Summary

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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

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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.

Conditions

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HIV Infections AIDS

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Infusion of autologous CD34+ cells transduced with shRNAs targeting CCR5 and HIV genome
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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No busulfan preconditioning

shRNA-modified CD34+ cells without busulfan preconditioning.

Group Type EXPERIMENTAL

shRNA-modified CD34+ cells

Intervention Type BIOLOGICAL

Infusion of CD34+ cells transduced with shRNAs.

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.

Group Type EXPERIMENTAL

shRNA-modified CD34+ cells

Intervention Type BIOLOGICAL

Infusion of CD34+ cells transduced with shRNAs.

Low dose busulfan preconditioning

Intervention Type DRUG

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

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.

Group Type EXPERIMENTAL

shRNA-modified CD34+ cells

Intervention Type BIOLOGICAL

Infusion of CD34+ cells transduced with shRNAs.

Busulfan preconditioning

Intervention Type DRUG

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

Interventions

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shRNA-modified CD34+ cells

Infusion of CD34+ cells transduced with shRNAs.

Intervention Type BIOLOGICAL

Low dose busulfan preconditioning

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

Intervention Type DRUG

Busulfan preconditioning

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

Intervention Type DRUG

Other Intervention Names

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Busulfex Busulfex

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

50 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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R&D Kanglin Biotech

OTHER

Sponsor Role collaborator

Shanghai Public Health Clinical Center

OTHER_GOV

Sponsor Role lead

Responsible Party

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Hongzhou Lu

professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Hongzhou Lu, Ph.D

Role: STUDY_DIRECTOR

Caolang Road NO. 2901, Jinshan District, Shanghai

Locations

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Shanghai Public Health Clinical Center

Shanghai, Shanghai Municipality, China

Site Status RECRUITING

Countries

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China

Central Contacts

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Hongzhou Lu, M.D., Ph.D

Role: CONTACT

+86-021-37990333 ext. 3222

Li Liu, M.D., Ph.D

Role: CONTACT

86-021-37990333 ext. 3222

Facility Contacts

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Li Liu, Ph.D

Role: primary

86-021-37990333 ext. 3222

Other Identifiers

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KL1702

Identifier Type: -

Identifier Source: org_study_id

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