An Open-Label Safety, Tolerability, and Pharmacokinetics Study of Eteplirsen in Young Patients With Duchenne Muscular Dystrophy Amenable to Exon 51 Skipping
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 15
- 试验地点
- 4
- 主要终点
- Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and TEAEs Leading to Discontinuation From Study Drug
研究概览
简要总结
This is a multicenter, open-label, dose-escalation study to evaluate the safety, tolerability, and PK of once-weekly IV infusions of eteplirsen in approximately 12 male participants, ages 6 months to 48 months (inclusive), who have genotypically confirmed DMD with a deletion mutation amenable to exon 51 skipping.
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
- 6 Months 至 48 Months（Child）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Male between 6 months to 48 months of age (inclusive)
- •Diagnosis of DMD with a deletion mutation amenable to exon 51 skipping
- •Parent(s) or legal guardian(s) who is willing to provide written informed consent
排除标准
- •Received treatment that might have an effect on muscle strength or function within 12 weeks prior to dosing
- •Received previous or current treatment with any experimental treatment
- •Clinically significant illness other than DMD
- •Clinically significant laboratory abnormality
- •Any other condition that could interfere with the participation in the study.
研究组 & 干预措施
Eteplirsen
Eteplirsen will be administered once every 7 days by intravenous (IV) infusion starting on Day 1 for up to 96 weeks. The starting dose will be 2 milligrams/kilogram (mg/kg) eteplirsen, with escalation to 4, 10, 20, and 30 mg/kg for 10 weeks, and then participants will continue to receive eteplirsen at 30 mg/kg for the duration of the study.
干预措施: Eteplirsen (Drug)
结局指标
主要结局
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and TEAEs Leading to Discontinuation From Study Drug
时间窗: Baseline up to Week 100
TEAEs were defined as adverse events (AEs) with an onset following administration of the first dose of study drug. An AE was any untoward medical occurrence in a participant, which does not necessarily have a causal relationship with the study drug. Abnormalities presented at Baseline were considered AEs if they reoccurred after resolution or worsen during the AE collection period. An SAE was defined as any AE that, in the view of either the Investigator or Sponsor, resulted in any of the following outcomes as fatal, life-threatening, required hospitalization or prolongation of existing hospitalization, persistent or significant disability/incapacity, a congenital anomaly/birth defect, or an important medical event. A summary of all SAEs and Other AEs (nonserious) regardless of causality is located in the 'Adverse Events' Section.
Number of Participants With at Least 1 Markedly Abnormal Vital Sign
时间窗: Baseline up to Week 100
The vital sign parameters that were evaluated included blood pressure, heart rate, respiration, and temperature. A summary of all SAEs and Other AEs (nonserious) regardless of causality is located in the 'Adverse Events' Section.
Number of Participants With at Least 1 Potentially Clinically Significant Clinical Safety Laboratory Abnormality
时间窗: Baseline up to Week 100
Clinical laboratory parameters that were evaluated included * Any Grade ≥2 (moderate) or serious event without an alternative etiology that the Investigator deemed was related to study drug * Two consecutive drug-related serum creatinine levels ≥2\*upper limit of normal (ULN) without an alternative etiology * Creatine kinase (CK) levels \>50,000 units/liter (U/L) * A confirmed, unexplained, increase in gamma glutamyl transferase (GGT) \>3\*ULN and either an increase in bilirubin \>2\*ULN or nascent prothrombin time \>2\*ULN concurrently, without an alternative etiology
Abnormal Changes From Baseline or Worsening of Physical Examination Findings
时间窗: Baseline up to Week 100
Data not collected during the study for this Outcome Measure. A summary of all SAEs and Other AEs (nonserious) regardless of causality is located in the 'Adverse Events' Section.
Number of Participants With at Least 1 Markedly Abnormal Electrocardiogram (ECG) and Echocardiogram (ECHO)
时间窗: Weeks 8, 12, 24, 36, 48, 60, 72, 84, 96
The ECG was manually reviewed and interpreted by medically qualified personnel using a central vendor according to pre-specified criteria. The Investigator determined if the findings in the centrally read ECG report were clinically significant. Clinical significance was defined as any variation in ECG findings that had medical relevance resulting in an alteration in medical care. The ECHO was reviewed and interpreted by medically qualified personnel using a central vendor according to pre-specified criteria. The Investigator determined if the findings in the ECHO report were clinically significant. Clinical significance was defined as any variation in ECHO findings that had medical relevance resulting in an alteration in medical care. A summary of all SAEs and Other AEs (nonserious) regardless of causality is located in the 'Adverse Events' Section.
次要结局
- Time to Reach Maximum Plasma Concentration (Tmax) of Eteplirsen(Pre-infusion, immediately prior to end of infusion, and approximately 1-3 hours and 6-8 hours after completion of infusion during Weeks 2 (2 mg/kg dose level), 6 (10 mg/kg dose level), 8 (20 mg/kg dose level), and 10 and 24 (30 mg/kg dose level))
- Amount of Drug Eliminated in Urine(Pre-infusion, immediately prior to end of infusion, and approximately 1-3 hours and 6-8 hours after completion of infusion during Weeks 2 (2 mg/kg dose level), 6 (10 mg/kg dose level), 8 (20 mg/kg dose level), and 10 and 24 (30 mg/kg dose level))
- Area Under Concentration-Time Curve From Time 0 to the Last Quantifiable Concentration (AUClast) of Eteplirsen in Plasma(Pre-infusion, immediately prior to end of infusion, and approximately 1-3 hours and 6-8 hours after completion of infusion during Weeks 2 (2 mg/kg dose level), 6 (10 mg/kg dose level), 8 (20 mg/kg dose level), and 10 and 24 (30 mg/kg dose level))
- Maximum Plasma Concentration (Cmax) of Eteplirsen(Pre-infusion, immediately prior to end of infusion, and approximately 1-3 hours and 6-8 hours after completion of infusion during Weeks 2 (2 mg/kg dose level), 6 (10 mg/kg dose level), 8 (20 mg/kg dose level), and 10 and 24 (30 mg/kg dose level))