A Phase 1/2, Open-Label Study to Assess the Safety and Tolerability of Repeat Doses of Autologous T-Cells Genetically Modified at the CCR5 Gene by Zinc Finger Nucleases in HIV-Infected Subjects Following Cyclophosphamide Conditioning
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 8
- 主要终点
- Primary Outcome Measure
研究概览
简要总结
The purpose of this study is to evaluate the safety and tolerability of repeat doses of T-cell immunotherapy (SB-728mR-T) following cyclophosphamide conditioning.
CCR5 is a major co-receptor for HIV entry into T-cells. Disruption of CCR5 by zinc finger nuclease (SB-728mR), blocks HIV entry into the T-cells, therefore, protects the T-cells from HIV infection. Safety (primary outcome) and anti-viral effect (secondary outcome) of zinc finger nuclease-mediated CCR5 disrupted autologous T-cells (SB-728mR-T) will be evaluated in the study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female, 18 years of age or older with documented HIV diagnosis.
- •Must be willing to comply with study-mandated evaluations; including discontinuation of current antiretroviral therapy during the treatment interruption.
- •Initiated HAART therapy within (≤) 1 year of HIV diagnosis or suspected infection.
- •Undetectable HIV-1 RNA for at least 2 months prior to screening and at screening.
- •CD4+ T-cell count ≥500 cells/µL.
- •Absolute neutrophil count (ANC) ≥ 2500/mm
- •Platelet count ≥ 200,000/mm3.
排除标准
- •Acute or chronic hepatitis B or hepatitis C infection.
- •Active or recent (in prior 6 months) AIDS defining complication.
- •Any cancer or malignancy within the past 5 years, with the exception of successfully treated basal cell or squamous cell carcinoma of the skin or low grade (0 or 1) anal or cervical dysplasia.
- •Current diagnosis of NYHA grade 3 or 4 CHF, uncontrolled angina or uncontrolled arrhythmias.
- •History or any features on physical examination indicative of a bleeding diathesis.
- •Received HIV experimental vaccine within 6 months prior to screening, or any previous gene therapy using an integrating vector.
- •Use of chronic corticosteroids, hydroxyurea, or immunomodulating agents within 30 days prior to screening.
- •Use of Aspirin, dipyridamole, warfarin or any other medication that is likely to affect platelet function or other aspects of blood coagulation during the 2 week period prior to leukapheresis.
- •Currently participating in another clinical trial or participation in such a trial within 30 days prior to screening visit.
- •Currently taking maraviroc or have received maraviroc within 6 months prior to screening.
研究组 & 干预措施
Cohort 2
干预措施: SB-728mR-T (Genetic)
Cohort 2
干预措施: Cyclophosphamide (Drug)
Cohort 1
干预措施: SB-728mR-T (Genetic)
Cohort 1
干预措施: Cyclophosphamide (Drug)
结局指标
主要结局
Primary Outcome Measure
时间窗: 12 months
Number of Participants with Treatment related Adverse Events in subjects who received any portion of the SB-728mR-T infusion
次要结局
- Secondary Outcome Measure(Baseline and 12 months)