Clinical trial NCT03517631: 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
Overall status: UNKNOWN
Phase: PHASE1
Conditions: HIV Infections
AIDS
Keywords: HIV
AIDS
Lentivirus
shRNA
Multiplex
Gene therapy
Lead sponsor: Shanghai Public Health Clinical Center
Sponsor class: OTHER_GOV
Collaborators: name: R&D Kanglin Biotech
First posted: 2018-05-07
Enrollment: 6
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Infusion of autologous CD34+ cells transduced with shRNAs targeting CCR5 and HIV genome
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Adverse side effects
timeFrame: 18 months
Secondary outcomes:
measure: Efficacy of treatment
timeFrame: 18 months
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Shanghai Public Health Clinical Center
state: Shanghai
Study officials:
affiliation: Caolang Road NO. 2901, Jinshan District, Shanghai
name: Hongzhou Lu, Ph.D
role: STUDY_DIRECTOR
References: