A Phase 2B Extension Study of PTC124 in Subjects With Nonsense-Mutation-Mediated Duchenne and Becker Muscular Dystrophy
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 173
- 试验地点
- 37
- 主要终点
- Number of Participants With Treatment-Emergent Adverse Events (AEs)
研究概览
简要总结
Duchenne/Becker muscular dystrophy (DMD/BMD) is a genetic disorder that develops in boys. It is caused by a mutation in the gene for dystrophin, a protein that is important for maintaining normal muscle structure and function. Loss of dystrophin causes muscle fragility that leads to weakness and loss of walking ability during childhood and teenage years. A specific type of mutation, called a nonsense (premature stop codon) mutation is the cause of DMD/BMD in approximately 10-15% of boys with the disease. Ataluren (PTC124) is an orally delivered, investigational drug that has the potential to overcome the effects of the nonsense mutation. This study is a Phase 2b extension trial that will evaluate the long-term safety of ataluren (PTC124) in boys with nonsense mutation DMD/BMD, as determined by adverse events and laboratory abnormalities. The study will also assess changes in walking, muscle function, and other important clinical and laboratory measures.
详细描述
This is a Phase 2b, international, multicenter, open-label extension study for participants who successfully completed blinded study drug in Study 007. This extension study will evaluate the long-term administration of ataluren administered 3 times per day (TID) at morning, midday, and evening doses of 20, 20, and 40 milligrams/kilogram (mg/kg), respectively, in participants with nonsense mutation Duchenne/Becker muscular dystrophy (nmDBMD).
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
- 5 Years 至 —（Child, Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Completion of blinded study drug treatment in the previous Phase 2b study (PTC124-GD-007-DMD).
- •Ability to provide written informed consent (parental/guardian consent if applicable)/assent (if less than [<]18 years of age).
- •In participants who are sexually active, willingness to abstain from sexual intercourse or employ a barrier or medical method of contraception during PTC124 administration and the 6-week follow up period.
- •Willingness and ability to comply with scheduled visits, drug administration plan, study procedures, laboratory tests, and study restrictions.
排除标准
- •Known hypersensitivity to any of the ingredients or excipients of the study drug (Litesse® UltraTM [refined polydextrose], polyethylene glycol 3350, Lutrol® micro F127 [poloxamer 407], mannitol 25C, crospovidone XL10, hydroxyethyl cellulose, vanilla, Cab-O-Sil® M5P [colloidal silica], magnesium stearate).
- •Ongoing participation in any other therapeutic clinical trial.
- •Prior or ongoing medical condition (for example, concomitant illness, psychiatric condition, behavioral disorder, alcoholism, drug abuse), medical history, physical findings, ECG findings, or laboratory abnormality that, in the investigator's opinion, could adversely affect the safety of the subject, makes it unlikely that the course of treatment or follow up would be completed, or could impair the assessment of study results.
研究组 & 干预措施
Overall Participants: High-Dose Ataluren
All participants will receive ataluren suspension orally three times a day (TID), 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for up to 96 weeks in this study. Any participant who was receiving a reduced dose of ataluren at the end of treatment visit in study PTC124-GD-007-DMD, will be initiated ataluren therapy in this extension study at the 5-, 5-, and 10-mg/kg dose level; dose will be increased to 10, 10, and 20 mg/kg at Week 6 and to 20, 20, and 40 mg/kg at Week 12, if the preceding dose level is well tolerated.
干预措施: Ataluren (Drug)
结局指标
主要结局
Number of Participants With Treatment-Emergent Adverse Events (AEs)
时间窗: Baseline (Week 48 of Study 007) up to Week 102
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Severity of an AE was classified as: mild (does not interfere with usual function), moderate (interferes to some extent with usual function) and severe (interferes significantly with usual function). Drug-related AEs: AEs with a possible or probable relationship to study drug. Serious AEs: death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized participant and required medical intervention. TEAE: AE that occurred or worsened in the period extending from first dose of study drug in this study to 6 weeks after last dose of study drug in this study. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
Number of Participants With Clinically Significant Abnormal Laboratory Parameters
时间窗: Baseline (Week 48 of Study 007) up to Week 102
Laboratory parameters tests included hematology, biochemistry assay (hepatic, renal, and serum electrolyte values), adrenal assays, and urinalysis. Clinical significance was defined as per investigator's judgement.
次要结局
- Change From Baseline in 6-Minute Walk Distance (6MWD) at Week 60(Baseline (Week 48 of Study 007), Week 60)
- Change From Baseline in Mean Activity Period/Day/Visit at Week 60, as Assessed by Step Activity Monitoring (SAM)(Baseline (Week 48 of Study 007), Week 60)
- Change From Baseline in Maximum Continuous 10-minute, 20-minute, 30-minute, and 60-minute Total Step Count at Week 60, as Assessed by SAM(Baseline (Week 48 of Study 007), Week 60)
- Change From Baseline in Percentage of Time During Active Period Spent at No Activity (0 Steps/Minute[Min]), Low Activity (Less Than or Equal to [≤]15 Steps/Min), Medium Activity (16-30 Steps/Min), and High Activity (Greater Than[>]30 Steps/Min) at Week 60(Baseline (Week 48 of Study 007), Week 60)
- Change From Baseline in Time to Climb 4 Stairs at Week 60(Baseline (Week 48 of Study 007), Week 60)
- Change From Baseline in Mean Total Step Count/Hour During the Active Period at Week 60, as Assessed by SAM(Baseline (Week 48 of Study 007), Week 60)
- Change From Baseline in Heart Rate Before, During, and After Each 6MWD Test at Week 60, as Assessed by Heart Rate Monitoring With the Polar® RS400(Baseline (Week 48 of Study 007), Week 60)
- Change From Baseline in Participant-Reported HRQL as Measured by the Total Fatigue Scale Score at Week 60(Baseline (Week 48 of Study 007), Week 60)
- Change From Baseline in Number of Digits Recalled Forwards and Backwards on Digit Span Task at Week 60(Baseline (Week 48 of Study 007), Week 60)
- Trough Ataluren Plasma Concentration(Pre-morning dose (0 hour) at Baseline (Week 48 of 007 study), Weeks 54, 60, 72, 84, and 96)
- Change From Baseline in Mean Total Step Count/Day/Visit During the Active Periods at Week 60, as Assessed by SAM(Baseline (Week 48 of Study 007), Week 60)
- Change From Baseline in Time to Stand From Supine Position at Week 60(Baseline (Week 48 of Study 007), Week 60)
- Change From Baseline in Time to Walk/Run 10 Meters at Week 60(Baseline (Week 48 of Study 007), Week 60)
- Change From Baseline in Time to Descend 4 Stairs at Week 60(Baseline (Week 48 of Study 007), Week 60)
- Change From Baseline in Participant- Reported Health-Related Quality of Life (HRQL) as Measured by the Pediatric Quality of Life Inventory (PedsQL) Physical, Emotional, Social, and School Functioning Domain Scores at Week 60(Baseline (Week 48 of Study 007), Week 60)
- Study Drug Compliance(Baseline (Week 48 of Study 007) to Week 96)
- Change From Baseline in Parent/Caregiver- Reported HRQL as Measured by the PedsQL Physical, Emotional, Social, and School Functioning Domain Scores at Week 60(Baseline (Week 48 of Study 007), Week 60)
- Change From Baseline in Participant and Parent/Caregiver Reported Activities of Daily Living of Participants Who Were Unable to Complete the 6MWT (Nonambulatory Participants), as Measured by the Egen Klassifikation (EK) Scale at Week 60(Baseline (Week 48 of Study 007), Week 60)
- Change From Baseline in Parent/Caregiver-Reported HRQL as Measured by the Total Fatigue Scale Score at Week 60(Baseline (Week 48 of Study 007), Week 60)
- Change From Baseline in Parent/Caregiver-Reported Treatment Satisfaction Questionnaire for Medication (TSQM) Score at Week 60(Baseline (Week 48 of Study 007), Week 60)
- Change From Baseline in Serum Concentration of Creatine Kinase (CK) at Week 60(Baseline (Week 48 of Study 007), Week 60)