A Phase 3 Global, Randomized, Double-Blind, Placebo-Controlled, 48-Week, Parallel-Group Study of the Efficacy and Safety of Losmapimod in Treating Patients With Facioscapulohumeral Muscular Dystrophy (FSHD) (REACH)
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 260
- 试验地点
- 33
- 主要终点
- Part B: Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Parameters
研究概览
简要总结
This is a study to evaluate the safety and efficacy of losmapimod in treating participants with Facioscapulohumeral Muscular Dystrophy (FSHD). Participants diagnosed with Facioscapulohumeral muscular dystrophy type 1 (FSHD1) or Facioscapulohumeral muscular dystrophy type 2 (FSHD2) will participate in Part A (Placebo-controlled treatment period) and will be randomized in a 1:1 ratio to receive losmapimod 15 milligrams (mg) or placebo orally twice daily (BID). Upon completion of Part A, participants will have the option to rollover into Part B (open-label extension) to evaluate the long-term safety, tolerability, and efficacy of losmapimod and will receive losmapimod 15 mg orally BID.
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)
盲法说明
Part B of the study will be performed in an open-label fashion.
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants must be between 18 and 65 years of age, inclusive.
- •Genetically confirmed diagnosis of FSHD 1 or FSHD
- •Clinical severity score of 2 to 4 (Ricci Score; Range 0-5), at screening. Participants who are wheelchair-dependent or dependent on walker or wheelchair for activities are not permitted to enroll in the study.
- •Screening total RSA (Q1-Q4) without weight in the dominant UE assessed by RWS ≥ 0.2 and ≤ 0.
- •No contraindications to MRI.
排除标准
- •Previously diagnosed cancer that has not been in complete remission for at least 5 years. Localized carcinomas of the skin and carcinoma in situ of the cervix that have been resected or ablated for cure are not exclusionary.
- •Participants who are on drug(s) or supplements that may affect muscle function, as determined by the Investigator: participants must be on a stable dose of that drug(s) or supplement for at least 3 months prior to the first dose of study drug and remain on that stable dose for the duration of the study.
- •Known active opportunistic or life-threatening infections including Human Immunodeficiency virus (HIV) and hepatitis B or C.
- •Known active or inactive tuberculosis infection.
- •Acute or chronic history of liver disease.
- •Known severe renal impairment.
- •History of cardiac dysrhythmias requiring anti-arrhythmia treatment(s); or history or evidence of abnormal ECGs.
- •Use of another investigational product within 30 days or 5 half-lives (whichever is longer) or currently participating in a study of an investigational device.
- •Current or anticipated participation in a natural history study. Previous participation is allowed but participants cannot continue after enrollment in Study 1821-FSH-
- •Known hypersensitivity to losmapimod or any of its excipients.
- •Previous participation in a Fulcrum-sponsored FSHD losmapimod study (FIS-001-2019 or FIS-002-2019).
- •Note that all other inclusion and exclusion criteria are listed in the protocol and only key are presented.
研究组 & 干预措施
Part A: Placebo-controlled treatment period: Losmapimod
Participants will be randomized to receive losmapimod.
干预措施: Losmapimod (Drug)
Part A: Placebo-controlled treatment period: Placebo
Participants will be randomized to receive placebo
干预措施: Placebo oral tablet (Drug)
Part B: Open-label extension
Participants will receive losmapimod, upon completion of all assessments for Part A.
干预措施: Losmapimod (Drug)
结局指标
主要结局
Part B: Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Parameters
时间窗: Week 48 to Week 127
Twelve-lead ECGs were performed after participants has been recumbent for at least 5 minutes.
Part A: Change From Baseline in Total Relative Surface Area (RSA) Quadrants 1 to 5 (Q1-Q5) With 500 Grams (g) Wrist Weight Averaged Over Both Arms as Assessed by Reachable Workspace (RWS) at Week 48
时间窗: Baseline (Day 1) and at Week 48
Participants are instructed to complete a simple set of standardized movements of each arm centered around the shoulder joint. These arm movements are captured and quantitated with the use of a video camera. The RWS is a clinical outcome measure that measures the relative surface area that a participant may reach with an outstretched arm. Responses are rated on a scale of 0 (no reachable workspace) to 1.25 (maximal reachable workspace). Higher scores indicate better outcomes. Baseline is the last non-missing evaluation prior to first dose of study drug. Change from Baseline was calculated as the post-treatment value minus the value at Baseline.
Part B: Number of Participants Reporting Serious Treatment Emergent Adverse Events (Serious TEAEs) and Non-serious TEAEs > 5%
时间窗: Week 48 to Week 127
Treatment-emergent adverse event is an AE that begins on or after the first dose of study drug and on or before the stop of study drug + 35 days or begins before the first dose of study drug and worsens on or after the first dose of study drug and on or before the stop of study drug + 35 days. A SAE is defined as an AE that results in any of the following outcomes: death; life-threatening adverse event; inpatient hospitalization or prolongation of existing hospitalization; persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions; congenital anomaly/birth defect.
Part B: Number of Participants With Clinically Significant Changes in Chemistry Parameters
时间窗: Week 48 to Week 127
Blood samples were collected for the analysis of chemistry parameters: Glucose, sodium, potassium, calcium, inorganic phosphate, total protein, albumin, blood urea nitrogen, creatinine, total bilirubin, direct bilirubin, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, gamma glutamyl transferase and creatine phosphokinase.
Part B: Number of Participants With Clinically Significant Changes in Hematology Parameters
时间窗: Week 48 to Week 127
Blood samples were collected for the analysis of hematology parameters: hemoglobin (including mean corpuscular volume), mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, hematocrit, red blood cell count, total white blood cell count, platelet count. Differential blood counts, including basophils, eosinophils, neutrophils, lymphocytes, and monocytes
Part B: Number of Participants With Clinically Significant Changes in Urinalysis
时间窗: Week 48 to Week 127
Urine samples were collected for the analysis of urinalysis parameters: Leucocytes, blood, nitrite, protein, urobilinogen, bilirubin, potential of Hydrogen (pH), specific gravity, ketones, glucose.
Part B: Number of Participants With Clinically Significant Changes in Vital Parameters
时间窗: Week 48 to Week 127
Vital parameters including pulse rate, respiration rate, blood pressure, and temperature were measured in seated or recumbent for at least 5 minutes. Data for number of participants with abnormal clinically significant changes for vital signs have been presented.
Part B: Number of Participants With Clinically Significant Changes in Physical Examinations
时间窗: Week 48 to Week 127
Physical examinations included an evaluation of body systems, including but not limited to the following: skin; head, eyes, ears, nose, and throat; respiratory system; cardiovascular system; abdomen (liver, spleen); lymph nodes; neurological system; and musculoskeletal system.
次要结局
- Part A: Number of Participants With Clinically Significant Changes in Clinical Chemistry Parameters(Up to Week 48)
- Part A: Change From Baseline in Quality of Life in Neurologic Disorders Upper Extremity (Neuro-QoL UE) Scale at Week 48(Baseline (Day 1) and at Week 48)
- Part A: Change From Baseline in Whole Body (WB) Longitudinal Composite Muscle Fat Infiltration (MFI) of B Muscles at Week 48(Baseline (Day 1) and at Week 48)
- Part A: Relative Change From Baseline in Average Shoulder Abductor Strength by Hand-held Quantitative Dynamometry at Week 48(Baseline (Day 1) and at Week 48)
- Part A: Number of Participants Serious TEAEs and TEAEs(Up to Week 48)
- Part A: Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Parameters(Up to Week 48)
- Part A: Number of Participants With Response to Patient's Global Impression of Change (PGIC) at Week 48(At Week 48)
- Part A: Number of Participants With Clinically Significant Changes in Hematology Parameters(Up to Week 48)
- Part A: Number of Participants With Clinically Significant Changes in Urinalysis(Up to Week 48)
- Part A: Number of Participants With Clinically Significant Changes in Vital Parameters(Up to Week 48)
- Part A: Number of Participants With Clinically Significant Changes in Physical Examinations(Up to Week 48)