A Multi-Center, Open-Label Study of Sebelipase Alfa in Patients With Lysosomal Acid Lipase Deficiency
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 31
- 主要终点
- Participants Experiencing Severe Treatment-emergent Adverse Events (TEAEs)
研究概览
简要总结
This study evaluated the safety and efficacy of sebelipase alfa in a broad population of participants with lysosomal acid lipase deficiency (LAL-D).
详细描述
The primary objective of this study was to evaluate the safety of intravenous (IV) infusions of sebelipase alfa in a more broad population of LAL-D participants than previously studied. Such participants may have been excluded from enrollment in other studies of LAL-D because of age, disease progression, previous treatment by hematopoietic stem cell or liver transplantation, less common disease manifestations, or disease characteristics that would preclude participation in a placebo-controlled study. This open-label study included infants >8 months, children, and adults. At least 4 participants in the study were to be between the age of 2 and 4 years. Eligible participants received sebelipase alfa at a dose of 1 milligram/kilogram (mg/kg) every other week (qow).
研究设计
- 研究类型
- Interventional
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 8 Months 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participant was >8 months of age at the time of dosing.
- •Confirmation of LAL-D diagnosis as determined by the central laboratory or, for participants with prior hematopoietic stem cell transplant or liver transplant, historical enzyme activity or molecular genetic testing confirming a diagnosis of LAL-D.
- •Participants >8 months but <4 years of age at Screening had at least 1 of the following documented clinical manifestations of LAL-D:
- •Dyslipidemia
- •Elevated transaminases
- •Impaired growth
- •Suspected malabsorption
- •Other clinical manifestation of LAL-D
- •Participants ≥4 years of age at Screening had at least 1 of the following documented clinical manifestations of LAL-D:
- •Evidence of advanced liver disease
- •Histologically confirmed disease recurrence in participants with past liver or hematopoietic transplant
- •Persistent dyslipidemia
- •Suspected malabsorption
- •Other clinical manifestation of LAL-D
排除标准
- •Participant had known causes of active liver disease other than LAL-D, which had not been adequately treated.
- •Participant received a hematopoietic stem cell or liver transplant <2 years from the time of dosing.
- •Participant with co-morbidities other than complications due to LAL-D, which were irreversible or associated with a high mortality risk within 6 months or would interfere with study compliance or data interpretation.
研究组 & 干预措施
Sebelipase Alfa
Pediatric and adult participants initiated IV treatment with sebelipase alfa at a dose of 1 mg/kg qow. Participants were considered for a dose adjustment at the discretion of the Investigator and in consultation with the Sponsor. Dose escalation to 3 mg/kg qow was considered if pre-defined dose-escalation criteria were met. If these criteria continued to be met, a subsequent dose escalation to 3 mg/kg every week (qw) was considered. Dose decreases as low as 0.35 mg/kg qow were permitted based upon evidence of intolerance to sebelipase alfa treatment. Participants who completed the 96-week treatment period were permitted to continue receiving sebelipase alfa in an expanded treatment period for up to 48 weeks, pending local drug availability and study participation status.
干预措施: Sebelipase Alfa (Drug)
结局指标
主要结局
Participants Experiencing Severe Treatment-emergent Adverse Events (TEAEs)
时间窗: Screening, Week 144
The number of participants experiencing severe TEAEs is presented for participants who received sebelipase alfa in this open-label study. Adverse events (AEs) information was obtained at each scheduled contact with the participant (or participant's parent or legal guardian). An AE was defined as any untoward medical occurrence that did not require a causal relationship with study drug administration. An AE could have been any unfavorable and unintended sign, symptom, or disease temporally associated with the use of the study drug, whether or not considered related to the study drug. Pre-existing conditions that worsened in severity during the study were reported as AEs. A summary of all serious and other non-serious AEs regardless of causality is located in the Reported AE module. Severity assessed using Clinical Data Interchange Standards Consortium Study Data Tabulation Model standard terminology v3.1.1. Data presented only according to age group, not dose of study drug received.
次要结局
- Participants Testing Positive For Anti-drug Antibodies (ADAs)(Week 144)
- Percent Change In Body Mass Index (BMI)-For-Age Percentile From Baseline To Week 144 In Pediatric Participants(Baseline, Week 144)
- Percent Change In Serum Lipids From Baseline To Week 144(Baseline, Week 144)
- Shift In Child-Pugh Status From Baseline To Week 144(Baseline, Week 144)