A Phase 1/2 Open-label, Dose Escalation Study Followed by a Multi-center, Randomized, Double-blind, Dose Comparison Study to Evaluate the Efficacy, Safety, Tolerability, Pharmacokinetics of CAN103 in Newly Treated Gaucher Disease
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Mean change in hemoglobin level from Baseline to Week 39 in the high-dose group
研究概览
简要总结
Gaucher disease is a rare lysosomal storage disorder caused by deficient activity of the enzyme acid β-glucosidase, causing glucosylceramide to accumulate within macrophages and leading to hepatosplenomegaly, anemia, thrombocytopenia, and bone disease. In the non-neuronpathic form (type 1), disease manifestations are mostly systemic, whereas in the neuronopathic forms, glucosylceramide also accumulates in the central nervous sysem and leads to acute (type 2) or chronic (type 3) neurodegeneration. The purpose of this Phase 1/2 first-in-human study is to initially evaluate the safety and tolerability of two doses of CAN103, and then barring any safety concerns, to evaluate the efficacy and safety of the two doses administered intravenously every other week in treatment-naive subjects with Gaucher disease type 1 or type 3.
详细描述
Phase 1: 4 newly treated subjects with Type I Gaucher disease (GD1). Phase 2: 36 newly treated subjects with GD1 or Type III Gaucher disease (GD3)
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Phase 2 is blinded to dose group. Except for the non-blind team, no other participants associated with this study should attempt to learn the treatment group assignment or which study treatment they are receiving. The unblinding of all subjects will take place after database lock.
入排标准
- 年龄范围
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects have a confirmed clinical, enzymatic, and genetic diagnosis of Gaucher disease (Type 1 or Type 3);
- •Phase 1: Subjects with GD1 aged ≥18 years; Phase 2: Subjects with GD1 or GD3 aged ≥12 years;
- •Subjects have not received enzyme replacement therapy (ERT) or substrate replacement therapy (SRT) within 3 months before screening;
- •Subjects have GD-related anemia and one or more of the following disease manifestations:
- •Spleen volume ≥2 MN as measured by MRI, or
- •Liver volume ≥1.5 MN as measured by MRI, or
- •Platelet count ≥20 × 10^9/L and <100×10^9/L.
排除标准
- •Subjects have received or stopped treatment with other investigational drugs or devices within 30 days before screening or less than 5 half-lives, whichever is longer (drugs only);
- •Subjects have anemia due to other causes during screening, including nutritional anemia. Subjects whose nutritional anemia recovers with the treatment of iron, folic acid, or Vitamin B12 may be rescreened;
- •Subjects have received hepatectomy or splenectomy;
- •Subjects have had an allergic reaction to imiglucerase or other ERTs and their components;
- •Subjects have received treatment with erythropoietin, whole blood or packed red blood cell transfusions, or chronic systemic corticosteroids within 3 months before screening, or have received a platelet transfusion within 1 month before screening.
研究组 & 干预措施
Low-dose CAN103
Low dose intravenous infusion of CAN103 every other week for 37 weeks
干预措施: Low-dose CAN103 (Drug)
High-dose CAN103
High dose intravenous infusion of CAN103 every other week for 37 weeks
干预措施: High-dose CAN103 (Drug)
结局指标
主要结局
Mean change in hemoglobin level from Baseline to Week 39 in the high-dose group
时间窗: Baseline to Week 39
Hemoglobin is measured in a central laboratory. An increase from Baseline indicates a therapeutic response.
次要结局
- Mean change in hemoglobin level from Baseline to Week 39 in the low-dose group.(Baseline and Week 39)
- Mean percent change in platelet count from Baseline to Week 39 in the low-dose and high-dose groups.(Baseline to Week 39)
- Mean percent change in liver volume (multiples of normal, MN) measured by magnetic resonance imaging (MRI) from Baseline to Week 39 in the low-dose and high-dose groups.(Baseline to Week 39)
- Mean percent change in spleen volume (MN) measured by MRI from Baseline to Week 39 in the low-dose and high-dose groups.(Baseline to Week 39)