A Phase 1b, Open-label Study of the Safety and Pharmacokinetics of EDG-5506 in Adults With Becker Muscular Dystrophy
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- Percentage of Participants Treated With Sevasemten Experiencing AEs
研究概览
简要总结
The ARCH study was an open-label, single-center, Phase 1b study of sevasemtem (EDG-5506) to assess the safety and pharmacokinetics (PK) of sevasemten in adults with Becker muscular dystrophy (BMD).
Sevasemten is an investigational product intended to protect and improve function of dystrophic muscle fibers.
详细描述
This open-label study evaluated the safety, tolerability, and pharmacokinetics (PK) of sevasemten in participants with BMD who completed the first-in-human study, EDG-5506-001, as well as additional (treatment-naïve) participants from outside the EDG-5506-001 study to meet the target sample size.
All participants received sevasemten. This study had a 24 month treatment period, followed by an optional 4 week follow-up period. On-site visits occurred approximately monthly for the first 12 months, followed by every 3 months to assess safety and measures of function.
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
- 18 Years 至 55 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Participants who have completed Study EDG-5506-
- •Participants who were not from Study EDG-5506-001 must meet the following:
- •Male sex at birth and aged 18 to 55 years inclusive at time of consent.
- •Documented dystrophin mutation with phenotype consistent with BMD.
- •Ambulatory at Screening (defined as ability to complete 100 meter [m] timed test, with or without assistance).
- •Body weight ≥ 50 kg at the Screening visit.
- •Body mass index (BMI) between 20 and 34 kg/m2 inclusive.
- •Female sexual partners of male participants must use highly effective contraception (<1% failure rate per year) through 6 months after last dose.
- •Capable of giving signed informed consent.
排除标准
- •Any clinically significant changes during or following the completion of Study EDG 5506-001 that would affect the potential safety of the participant to receive EDG
- •Cardiac echocardiogram ejection fraction <45% or New York Heart Association (NYHA) Class III or Class IV.
- •Baseline 12-lead electrocardiogram (ECG) that demonstrates clinically relevant abnormalities that may affect participant safety or interpretation of study results.
- •Forced vital capacity (FVC) predicted <65% or using daytime (mechanical or noninvasive) ventilatory support.
- •Moderate or severe renal or hepatic impairment (eGFR <60 mL/min/1.73 m2).
- •Positive test for hepatitis C antibody (unless negative HCV PCR), hepatitis B surface antigen, or human immunodeficiency virus (HIV) antibody at screening.
- •History of substance abuse or dependency.
- •Receipt of oral corticosteroids for >5 days in the previous 6 months at a dose of >5 mg equivalent per day. Lower oral doses or inhaled/intranasal steroids are permitted.
- •Receiving moderate or strong cytochrome P450 CYP3A4 inhibitors or inducers.
- •Participation in any other investigational drug study or use of use of an investigational drug within 30 days or 5 half-lives (whichever is longer) of dosing in the present study.
- •Participants who are unlikely to comply with the study protocol or, in the opinion of the Investigator, would not be a suitable candidate for participation in the study.
- •Medical history or other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory result or abnormality that may increase the risk of study participation or, in the Investigator's judgment, make the participant inappropriate for the study. Includes venous access that would be too difficult to facilitate repeated blood sampling.
研究组 & 干预措施
Treatment
Drug: Sevasemten
干预措施: Sevasemten (Drug)
结局指标
主要结局
Percentage of Participants Treated With Sevasemten Experiencing AEs
时间窗: From first dose of study drug to 25 months
An AE is any untoward medical occurrence in a patient administered a medicinal product. The AE does not necessarily have to have a causal relationship with the study drug. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. The numerator of the percentage is the number of participants experiencing at least one AE after first dose of study drug up to 25 months.
Frequency of AEs in Those Treated With Sevasemten
时间窗: From first dose of study drug to 25 months
An AE is any untoward medical occurrence in a patient administered a medicinal product. The AE does not necessarily have to have a causal relationship with the study drug. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. The endpoint is the cumulative total number of AEs occurring after first dose of study drug up to 25 months among participants who received at least one dose of study drug.
Number of Participants Treated With Sevasemten With AEs by Maximum Severity
时间窗: From first dose of study drug to 25 months
An AE is any untoward medical occurrence in a patient administered a medicinal product. The AE does not necessarily have to have a causal relationship with the study drug. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. The severity of an AE is graded, according to the study protocol definitions of AE severity/intensity, as "mild", "moderate" or "severe". Participants who reported multiple AEs are counted only once at the highest severity reported.
次要结局
- Percentage of Participants Experiencing Treatment-Emergent Abnormal Clinical Chemistry Test Results(From first dose of study drug to 25 months)
- Percentage of Participants Experiencing Treatment-Emergent Abnormal Hematology Test Results(From first dose of study drug to 25 months)
- Percentage of Participants Experiencing Treatment-Emergent Abnormal Coagulation Test Results(From first dose of study drug to 25 months)
- Percentage of Participants Experiencing Treatment-Emergent Abnormal Urinalysis Test Results(From first dose of study drug to 25 months)
- Number of Participants With Clinically Significant Changes in Clinical Chemistry(From first dose of study drug to 24 months)
- Number of Participants With Clinically Significant Changes in Hematology(From first dose of study drug to 24 months)
- Number of Participants With Clinically Significant Changes in Coagulation(From first dose of study drug to 24 months)
- Number of Participants With Clinically Significant Changes in Urinalysis(From first dose of study drug to 24 months)
- Number of Participants With Clinically Significant Changes in Vital Signs(From first dose of study drug to 24 months)
- Number of Participants With Clinically Significant Changes in Physical and Neurological Examinations(From first dose of study drug to 24 months)
- Number of Participants With Clinically Significant Changes in ECG PR Interval(From first dose of study drug to 24 months)
- Number of Participants With Clinically Significant Changes in ECG QRS Interval(From first dose of study drug to 24 months)
- Number of Participants With Clinically Significant Changes in ECG QT Interval(From first dose of study drug to 24 months)
- Number of Participants With Clinically Significant Changes in ECG QTc Interval(From first dose of study drug to 24 months)
- Number of Participants With Clinically Significant Changes in Forced Vital Capacity (FVC)(From first dose of study drug to 24 months)
- Number of Participants With Clinically Significant Changes in Forced Expiratory Volume in 1 Second (FEV1)(From first dose of study drug to 24 months)
- Number of Participants With Clinically Significant Changes in Cardiac Function as Assessed by Echocardiogram(From first dose of study drug to 24 months)
- Number of Participants With Clinically Significant Changes in Columbia Suicide Severity Rating Scale (C-SSRS)(From first dose of study drug to 24 months)
- Plasma Sevasemten (EDG-5506) Concentrations at Sample Timepoints(Pre-dose; 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, and 24 hours post-dose; 29 and 57 days post-dose; 3, 4, 6, 7, 8, 10, 12, 15, 18, 21, and 24 months post-dose.)