Phase 3 Study to Compare Oral Masitinib to Placebo in Treatment of Patients With Smouldering or Indolent Severe Systemic Mastocytosis, Unresponsive to Optimal Symptomatic Treatment
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 140
- 试验地点
- 17
- 主要终点
- Cumulative response (3R75%)
研究概览
简要总结
The purpose of this study is to evaluate the efficacy and safety of oral masitinib versus placebo in the treatment of patients suffering from smouldering or indolent systemic mastocytosis with severe symptoms of mast cell mediator release, unresponsive to optimal symptomatic treatment.
详细描述
Masitinib is a selective tyrosine kinase inhibitor that modulates mast cell activity via inhibition of c-Kit, Lyn and Fyn kinase signaling pathways. This is a multicenter, randomized, double-blind, placebo-controlled, 2-parallel-group, trial comparing oral masitinib versus placebo in the treatment of patients suffering from smouldering or indolent systemic mastocytosis with severe symptoms of mast cell mediator release (also referred to as handicaps), unresponsive to optimal symptomatic treatment. The treatment period is 24 weeks. Participants receive masitinib (3.0 mg/kg/day), given orally twice daily, with a dose escalation to 4.5 mg/kg/day after 4 weeks of treatment, followed by dose escalation to 6.0 mg/kg/day after 4 weeks of treatment. Each ascending dose titration is subjected to a safety control.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patient with one of the following documented mastocytosis subtypes (variants): Smouldering Systemic Mastocytosis, Indolent Systemic Mastocytosis
- •An excess of mast cells or a presence of abnormal mast cells in at least two organs (among skin, bone-marrow and GI Tract).
- •Patient with documented systemic mastocytosis and evaluable disease based upon histological criteria
- •Patient with documented treatment failure of his/her symptom(s) (within the past 2 years) with at least two of the symptomatic treatments used at optimized dose: Anti H1, Anti H2, Proton pump inhibitor, Antidepressants, Cromoglycate Sodium, Antileukotriene.
- •Patient with severe symptoms of mastocytosis over the 14-day run-in period including at least one among pruritus, flushes, and depression: pruritus score ≥ 9, number of flushes per week ≥ 8, Hamilton rating scale for depression (HAMD-17) score ≥ 19.
排除标准
- •Patient with one of the following mastocytosis: Cutaneous Mastocytosis, Systemic Mastocytosis with an Associated clonal Hematologic Non Mast cell lineage Disease (SM-AHNMD), Mast cell leukemia (MCL), Aggressive systemic mastocytosis (ASM)
- •Previous treatment with any Tyrosine Kinase Inhibitor
- •Treatment with any investigational agent within 8 weeks prior to screening.
研究组 & 干预措施
Masitinib & BSC
Experimental Arm:
Masitinib (titration to 6.0 mg/kg/day) administered as an add-on to optimal concomitant symptomatic treatment (i.e. best supportive care, BSC).
Participants receive masitinib (3.0 mg/kg/day), given orally twice daily, with a dose escalation to 4.5 mg/kg/day after 4 weeks of treatment, followed by dose escalation to 6.0 mg/kg/day after 4 weeks of treatment. Each ascending dose titration is subjected to a safety control.
干预措施: Masitinib (Drug)
Masitinib & BSC
Experimental Arm:
Masitinib (titration to 6.0 mg/kg/day) administered as an add-on to optimal concomitant symptomatic treatment (i.e. best supportive care, BSC).
Participants receive masitinib (3.0 mg/kg/day), given orally twice daily, with a dose escalation to 4.5 mg/kg/day after 4 weeks of treatment, followed by dose escalation to 6.0 mg/kg/day after 4 weeks of treatment. Each ascending dose titration is subjected to a safety control.
干预措施: Best Supportive Care (Other)
Placebo & BSC
Placebo Comparator:
Matching placebo administered as an add-on to optimal concomitant symptomatic treatment (i.e. best supportive care, BSC)
干预措施: Placebo (Other)
Placebo & BSC
Placebo Comparator:
Matching placebo administered as an add-on to optimal concomitant symptomatic treatment (i.e. best supportive care, BSC)
干预措施: Best Supportive Care (Other)
结局指标
主要结局
Cumulative response (3R75%)
时间窗: 24 weeks
Cumulative response in at least one of three severe baseline symptoms of mast cell mediator release (pruritus, flushes, or depression). Response was defined as a 75% improvement from baseline for any of these three symptoms. Cumulative response was defined as the number of actual responses between weeks 8 and 24, divided by the total number of possible responses over the same treatment period (ie, with five scheduled visits, each patient had a maximum of five to 15 possible responses depending on the number of severe baseline symptoms).
次要结局
- Cumulative response(24 weeks)
- Cumulative response (4R75%)(24 weeks)
- Cumulative response (2R75%)(24 weeks)