A Phase I Clinical Trial for Gene Therapy in Infantile Malignant Osteopetrosis (IMO) to Evaluate the Safety and Preliminary Efficacy of Autologous CD34+ Enriched Cells Transduced With a LV Vector Encoding the TCIRG1 Gene
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 1
- 试验地点
- 1
- 主要终点
- Number of participants with treatment-related adverse events as assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0
研究概览
简要总结
The primary objective of this Phase 1 study is to evaluate the therapeutic safety and feasibility of the investigational product (IP), RP-L401.
详细描述
This is a non-randomized Phase 1 study to evaluate the preliminary safety and efficacy of hematopoietic gene therapy consisting of autologous CD34+ enriched hematopoietic cells transduced with the lentiviral vector (LV) carrying the human TCIRG1 transgene (RP-L401) in pediatric patients with IMO. Following myeloablative conditioning patients will receive an infusion of the genetically modified hematopoietic stem and progenitor cells (HSPCs).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 1 Month 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •A confirmed diagnosis of IMO with documented TCIRG1 mutation.
- •Age at least 1 month with minimum weight of 4 kg
- •Absence of debilitating hydrocephalus (defined as hydrocephalus at NCI CTCAE v5.0 Grade 3 or higher persisting despite shunt or similar procedural intervention).
- •Lansky Play Scale of at least 60%
- •Preserved hepatic function (AST/ALT ≤3.0 ULN; bilirubin ≤1.5 ULN; to minimize potential for excessive toxicity from busulfan conditioning)
- •No concomitant medical or other conditions that would represent a contraindication to autologous hematopoietic stem cell transplant.
- •Absolute neutrophil count of ≥500/mm3 and platelet count of ≥25,000/mm3
- •No prior allogeneic or other hematopoietic stem cell transplant.
- •Availability of a non-autologous rescue (back-up) hematopoietic stem cell donor/source
排除标准
- •Availability of medically-feasible HLA-matched sibling donor for allogeneic HSCT.
- •Any medical or other contraindication for either apheresis or autologous transplant as determined by the Investigator.
- •Participation in another clinical trial with an investigational drug within 14 days before the informed consent signature. Participation in observational studies is allowed.
- •Active hematologic or solid organ malignancy, not including non-melanoma skin cancer or another carcinoma in situ.
- •Uncontrolled seizure disorder.
- •Renal dysfunction as defined by a glomerular filtration rate <30 mL/min/1.73m2 or dialysis dependence.
- •Serious infections with persistent bloodstream pathogens at time of trial entry
- •Pulmonary dysfunction as defined by either:
- •Need for supplemental oxygen during the prior 2 weeks (in absence of acute infection) or
- •Oxygen saturation (by pulse oximetry) <90% resulting from pulmonary conditions (intermittent hypoxia secondary to IMO-related choanal atresia will not be considered exclusionary)
研究组 & 干预措施
Experimental - RP-L401
RP-L401 is a gene therapy product containing autologous genetically modified CD34+ hematopoietic cells transduced with lentiviral vector carrying the TCIRG1 transgene
干预措施: RP-L401 (Biological)
结局指标
主要结局
Number of participants with treatment-related adverse events as assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0
时间窗: 2 years
Evaluation of safety associated with treatment with RP-L401
次要结局
- Assessment of blood counts after infusion of RP-L401(2 years)
- Assessment of hepatosplenomegaly after infusion of RP-L401(2 years)
- Assessment of head, mouth and gum abnormalities(2 years)
- Assessment of vector copy number (VCN) after infusion of RP-L401(2 years)
- Assessment of endocrine and metabolic status after infusion of RP-L401(2 years)
- Assessment of bone abnormalities after infusion of RP-L401(2 years)
- Assessment of auditory status after infusion of RP-L401(2 years)
- Assessment of ophthalmology status after infusion of RP-L401(2 years)