A Multi-Part, Randomized, Double-Blind, Placebo-Controlled Phase 2 Clinical Study of The Safety and Efficacy of CGT9486 in Subjects With Nonadvanced Systemic Mastocytosis
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 237
- 试验地点
- 103
- 主要终点
- Part 1: Determine recommended dose of bezuclastinib (CGT9486) in subjects with NonAdvSM
研究概览
简要总结
This is a multi-part, randomized, double-blind, placebo-controlled Phase 2 clinical study comparing the safety and efficacy of bezuclastinib (CGT9486) plus best supportive care (BSC) with placebo plus BSC in patients with nonadvanced systemic mastocytosis (NonAdvSM), including indolent systemic mastocytosis and smoldering systemic mastocytosis, whose symptoms are not adequately controlled by BSC. This study will be conducted in three parts. Patients in Parts 1a, 1b and 2 will receive bezuclastinib or placebo, and may roll over onto Part 3 to receive treatment with bezuclastinib. Additionally, a substudy of subjects will investigate the efficacy, safety, and tolerability of bezuclastinib in patients who are experiencing inadequate symptom control with avapritinib.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosed with 1 of the following diagnoses according to the 2016 World Health Organization (WHO) classification for systemic mastocytosis (SM):
- •Indolent systemic mastocytosis (ISM),
- •Bone marrow mastocytosis (BMM)
- •Smoldering systemic mastocytosis (SSM)
- •Moderate-to-severe symptoms based on a minimum total symptom scoew (TSS) of the Mastocytosis Activity Score (MAS) and after establishing a stable regimen of at least 2 antimediator therapies over a 14-day eligibility period
- •Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to 2
- •For patients receiving corticosteroids, the dose must be ≤10 mg/day of prednisone or equivalent
排除标准
- •Persistent toxicity from previous therapy for NonAdvSM that has not resolved to ≤ Grade 1
- •Diagnosed with any of the following WHO SM classifications: bone marrow mastocytosis, advanced systemic mastocytosis including SM with associated hematologic neoplasm, aggressive SM, mast cell leukemia; or mast cell sarcoma
- •Diagnosed with mastocytosis of the skin without systemic involvement
- •Received prior treatment with any targeted KIT inhibitor with the exception of approved agents for the treatment of SM
- •Received prior cytoreductive therapy or investigational agent for <14 days or 5 half- lives of the drug and for cladribine, interferon alpha, pegylated interferon, or antibody therapy <28 days or 5 half-lives of the drug (whichever is longer), before starting screening assessments
- •Received radiotherapy or psoralen and ultraviolet A therapy <14 days before starting screening assessments
- •Received any hematopoietic growth factor support <14 days or 5 half lives of the drug before starting screening assessments
- •History of clinically significant bleeding event within 30 days before the first dose of study drug or need for therapeutic anticoagulation on study
- •Need for treatment of corticosteroids at >10 mg/day of prednisone or equivalent
- •Received strong CYP3A4 inhibitors or inducers within 14 days or 5 drug half-lives before the first dose of study drug
研究组 & 干预措施
(Part 3) Bezuclastinib + BSC
干预措施: Bezuclastinib Tablets (Formulation A) (Drug)
(Part 2) Placebo + BSC
干预措施: Placebo Tablets (Drug)
(Part 1b) Bezuclastinib Dose 1 + BSC
干预措施: Bezuclastinib Tablets (Formulation B) (Drug)
(Part 1b) Bezuclastinib Dose 2 + BSC
干预措施: Bezuclastinib Tablets (Formulation B) (Drug)
(Part 1a) Placebo + BSC
干预措施: Placebo Tablets (Drug)
(Part 1b) Placebo + BSC
干预措施: Placebo Tablets (Drug)
(Part 1a) Bezuclastinib Dose 2 + BSC
干预措施: Bezuclastinib Tablets (Formulation A) (Drug)
(Part 1a) Bezuclastinib Dose 1 + BSC
干预措施: Bezuclastinib Tablets (Formulation A) (Drug)
(Prior Therapy Sub-study) Bezuclastinib
干预措施: Bezuclastinib Tablets (Formulation B) (Drug)
(Part 3) Bezuclastinib + BSC
干预措施: Bezuclastinib Tablets (Formulation B) (Drug)
(Part 2) Bezuclastinib Selected Dose + BSC
干预措施: Bezuclastinib Tablets (Formulation B) (Drug)
结局指标
主要结局
Part 1: Determine recommended dose of bezuclastinib (CGT9486) in subjects with NonAdvSM
时间窗: 3 months
Selection of the recommended dose to be used in subsequent parts of the study.
Part 2: Efficacy of bezuclastinib at the selected dose versus placebo
时间窗: 24 Weeks
Mean absolute change on the Mastocytosis Symptom Severity Daily Diary (MS2D2)
Part 3: Safety and tolerability of bezuclastinib as assessed by number of adverse events
时间窗: Up to 5 years
CTCAE v5
次要结局
- Part 2: Proportion of subjects who had at least 50% reduction in serum tryptase(24 weeks)
- Part 2: Proportion of subjects who had at least a 50% reduction in peripheral blood D816V allele fraction(24 weeks)
- Part 2: Determine responder rates of subjects treated with bezuclastinib at the selected dose versus placebo(24 weeks)
- Part 2: Proportion of subjects who had at least 50% reduction in mast cell burden(24 weeks)
- Parts 1 & 2: Safety and tolerability of bezuclastinib as assessed by number of adverse events(Up to 24 weeks)
- Parts 1, 2, & 3: Change and percent change in patient reported outcome (PRO) measures(Up to 5 years)
- Parts 1 & 3: Change and percent change in serum tryptase(Up to 12 months)
- Parts 1 & 3: Change and percent change in bone marrow mast cells(Up to 18 months)
- Part 1: Assess the pharmacokinetics (PK) of bezuclastinib in subjects with NonAdvSM(3 months)
- Part 2: Determine mean change from baseline in predetermined PRO sub-domain and individual item scores(24 weeks)
- Parts 2 & 3: Determine change of the lead (most severe) symptom and lead (most severe) subdomain of the MS2D2 in subjects treated with bezuclastinib versus placebo(Up to 5 years)
- Part 3: Change and percent change in the levels of KIT D816V mutation allele burden(Up to 12 months)
- Part 3: To determine the efficacy of bezuclastinib at the selected dose(Up to 2 years)
- Part 3: Usage of concomitant medications as rescue therapy for NonAdvSM and changes from baseline in rescue therapy and best supportive care medications regimen(Up to 5 years)