TAM4MTM: A Phase 1/2 Randomized, Placebo-Controlled, Double-Blinded, Single Crossover Study to Determine the Safety and Efficacy of Tamoxifen Therapy for Myotubular Myopathy (XLMTM)
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 16
- 试验地点
- 4
- 主要终点
- Motor Function Measure 32 (MFM32)
研究概览
简要总结
This is a phase 1 / 2, randomized, double-blinded, single cross-over study, with a washout period between treatment regimens, to test the efficacy and safety of tamoxifen therapy to improve motor and respiratory function in males with XLMTM.
详细描述
Pre-clinical studies in Mtm1 knockout mice (a model of XLMTM) demonstrated prolonged survival, increased motor function (including muscle strength), and improved muscle histopathology with tamoxifen treatment. Based on these data, and the known safety profile of the drug in humans, we hypothesize that tamoxifen treatment will be safe and will improve motor and respiratory function in XLMTM patients. This is a randomized, double-blinded, single crossover clinical trial to test this hypothesis and determine the safety and efficacy of tamoxifen in improving motor and respiratory function in MTM patients. Each subject will serve as his own control during the placebo phase of the study. As treatments for XLMTM are current not available, this study addresses a critical unmet need by testing a therapy that, if effective, may serve as a primary treatment, or in the future as an adjunct to other therapies in development.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
The study is a placebo-controlled double-blinded design. A select few (pharmacist and study staff in charge of pharmacokinetics) and Data Safety Monitoring Board (DSMB) are unblinded.
入排标准
- 年龄范围
- 6 Months 至 —（Child, Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Placebo
Placebo (no active ingredients) tablets orally twice daily for 6 months
干预措施: Placebo (Drug)
Drug: ApoTamox 10mg
Drug: Tamoxifen (tamoxifen citrate); ApoTamox 10 mg tablets orally twice daily for 6 months
干预措施: ApoTamox 10mg (Drug)
结局指标
主要结局
Motor Function Measure 32 (MFM32)
时间窗: Baseline to 15 Months
Mean change from baseline of Motor Function Measure 32 for subjects aged 4 and older
Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders for subjects aged 2-4 years (CHOP INTEND)
时间窗: Baseline to 15 months
Mean change from baseline of Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders for subjects aged 2-4 years
10 meter walk test
时间窗: Baseline to 15 months
Mean change from baseline in velocity in 10 meter walk test for ambulant participants
次要结局
- Change in pulmonary function testing scores 4) Maximum Expiratory Pressure(Baseline to 15 months)
- Change in pulmonary function testing scores 1) Forced Expiratory Volume in the first second(Baseline to 15 months)
- Change in pulmonary function testing scores 2) Forced Vital Capacity(Baseline to 15 months)
- Change in pulmonary function testing scores 5) Maximum Inspiratory Pressure or Sniff Inspiratory Pressure(Baseline to 15 months)
- Change in pulmonary function testing scores 3) Peak Cough Flow(Baseline to 15 months)
- invasive ventilation - time off ventilation(Baseline to 15 months)
- Incidence and severity of Adverse Events related to the treatment [ Time Frame: 15 Months ](Baseline to 15 months)
- micro RNA 133a (miR133a)(Baseline to 15 months)
研究者
James Dowling
Staff clinician and senior scientist
The Hospital for Sick Children