A Phase 2, Open Label, Multicenter Study to Evaluate the Safety, Tolerability, Efficacy, and Pharmacokinetics of Sebelipase Alfa in Infants With Rapidly Progressive Lysosomal Acid Lipase Deficiency
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 10
- 主要终点
- Participants Experiencing Severe Treatment-emergent Adverse Events (TEAEs)
研究概览
简要总结
This was an open-label, repeat-dose, study of sebelipase alfa in infants with rapidly progressive lysosomal acid lipase deficiency (LAL-D). Eligible participants received once-weekly infusions of sebelipase alfa for up to 3 years.
详细描述
Lysosomal acid lipase deficiency is a rare autosomal recessive lipid storage disorder that is caused by a marked decrease or complete absence of the LAL enzyme, leading to the accumulation of lipids, predominately cholesteryl esters and triglycerides, in various tissues and cell types. In the liver, accumulation of lipids in hepatocytes and macrophages leads to hepatomegaly, fibrosis, cirrhosis, liver dysfunction, and hepatic failure. In the small intestine, lipid-laden macrophage accumulation in the lamina propria leads to profound malabsorption.
Lysosomal acid lipase deficiency presenting in infancy is an extremely rare form of the disease characterized by profound malabsorption, growth failure, and hepatic failure that is usually fatal within the first 6 months of life.
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
- — 至 8 Months（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participant's parent or legal guardian (if applicable) consent to participation in the study
- •Confirmation of documented decreased LAL activity relative to the normal range of the lab performing the assay or confirmation of LAL-D diagnosis as determined by a Sponsor-approved central laboratory
- •Substantial clinical concerns, in the opinion of Investigator and Sponsor, of rapid disease progression requiring urgent medical intervention including, but not restricted to the following:
- •Marked abdominal distension and hepatomegaly
- •Failure to thrive
- •Disturbance of coagulation
- •Severe anemia
- •Sibling with rapidly progressive course of LAL-D
排除标准
- •Clinically important concurrent disease
- •Participant was > 8 months of age at the time of first dosing
- •Participant received an investigational medicinal product other than sebelipase alfa within 14 days prior to the first dose of sebelipase alfa in this study
- •Myeloablative preparation, or other systemic pre-transplant conditioning, for hematopoietic stem cell or liver transplantation
- •Previous hematopoietic stem cell or liver transplant
- •Known hypersensitivity to eggs
研究组 & 干预措施
Open-Label Sebelipase Alfa
All participants initiated once weekly (qw) intravenous (IV) infusions with sebelipase alfa at a dose of 1 milligram/kilogram (mg/kg) qw. A participant who met protocol defined dose escalation criteria at a dose of 1 mg/kg qw could be considered for a dose escalation to 3 mg/kg qw. If a participant continued to meet dose escalation criteria after at least 4 infusions at a dose of 3 mg/kg qw, the participant could be considered for a further dose escalation to 5 mg/kg qw. Under country-specific provisions (United Kingdom only), participants could be considered for a further dose escalation to 7.5 mg/kg qw if a thorough case review indicated that a participant continued to have evidence of disease progression at a dose of 5 mg/kg qw. All dose escalations were contingent upon acceptable safety and tolerability of preceding infusions and were undertaken by mutual agreement of the Investigator and Sponsor and after approval by an independent safety committee.
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 through Month 37
The number of participants experiencing severe TEAEs is presented for participants who received sebelipase alfa in this open-label study. Adverse events were obtained through spontaneous reporting or elicited by specific questioning or examination of the participant's parent or legal guardian. An adverse event was defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in a participant, whether or not causally related to administration of study drug. Adverse event severity was graded by the Investigator as mild, moderate, or severe based on definitions developed from Clinical Data Interchange Standards Consortium Study Data Tabulation Model standard terminology v3.1.1. Adverse events reporting was from the date of informed consent until completion of the follow-up visit at approximately 30 days after the last dose of study drug. A summary of all serious and other nonserious AEs regardless of causality is located in the Reported AE module.
次要结局
- Change From Baseline In Serum Transaminases (ALT And AST) At Month 12, 24, And 36(Baseline, Month 12, Month 24, and Month 36)
- Percentage Of Participants Surviving To 12, 18, 24, And 36 Months Of Age(Baseline through Month 12, Month 18, Month 24, and Month 36)
- Median Age At Death(Baseline through Month 36)
- Number Of Participants With Stunting, Wasting, Or Underweight At Baseline, 12, 24, And 36 Months(Baseline to Month 12, Month 24, and Month 36)
- Change From Baseline In Serum Ferritin At Month 12, 24, And 36(Baseline, Month 12, Month 24, and Month 36)
- Change From Baseline In Percentiles For Weight For Age (WFA) At 12, 24, And 36 Months(Baseline, Month 12, Month 24, and Month 36)
- Number Of Participants Achieving And Maintaining Transfusion-free Hemoglobin Normalization (TFHN)(Baseline through Month 36)