An Open Label, Multicenter, Dose Escalation Study to Evaluate the Safety, Tolerability, Efficacy, Pharmacokinetics, and Pharmacodynamics of SBC-102 (Sebelipase Alfa) in Children With Growth Failure Due to Lysosomal Acid Lipase Deficiency
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 9
- 主要终点
- Percentage Of Participants In The Primary Efficacy Analysis Set (PES) Surviving To 12 Months Of Age
研究概览
简要总结
This was an open-label, repeat-dose, intra-participant dose-escalation study of SBC-102 (sebelipase alfa) in children with growth failure due to lysosomal acid lipase (LAL) Deficiency. Eligible participants received once-weekly (qw) infusions of sebelipase alfa for up to 5 years.
详细描述
LAL Deficiency is a rare autosomal-recessive lipid storage disorder that is caused by a marked decrease or almost complete absence of LAL, leading to the accumulation of lipids, predominately cholesteryl esters and triglycerides, in various tissues and cell types. In the liver, accumulation of lipids leads to hepatomegaly, liver dysfunction, and hepatic failure. Although a single disease, LAL Deficiency presents as a clinical continuum with 2 major phenotypes, Cholesteryl Ester Storage Disease (CESD) and Wolman Disease.
Early-onset LAL Deficiency (Wolman Disease) is extremely rare, with an estimated incidence of less than 2 lives per million. It is characterized by profound malabsorption, growth failure, and hepatic failure, and is usually fatal in the first year 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 24 Months（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participant's parent or legal guardian provided written informed consent/permission prior to any study procedures.
- •Male or female child with documented decreased LAL activity relative to the normal range of the laboratory performing the assay or documented result of molecular genetic testing (2 mutations) confirming a diagnosis.
- •Growth failure with onset before 6 months of age.
排除标准
- •Clinically important concurrent disease or comorbidities.
- •Had received an investigational product other than sebelipase alfa within 14 days prior to the first dose.
- •Participant was older than 24 months of age.
- •Myeloablative preparation, or other systemic pre-transplant conditioning, for hematopoietic stem cell or liver transplant.
- •Previous hematopoietic stem cell or liver transplant.
- •Known hypersensitivity to eggs.
研究组 & 干预措施
Open-Label Sebelipase Alfa
Participants received intravenous (IV) infusions of sebelipase alfa during the open-label treatment. Participants initially received 0.35 milligrams (mg)/kilogram (kg) qw and escalated to 1 mg/kg qw after demonstrating acceptable safety and tolerability during at least 2 infusions. One participant initiated treatment under a Temporary Use Authorization prior to enrollment, wherein the participant's dose was gradually escalated from 0.2 to 1 mg/kg over 4 weeks; the participant started the study at this dose. Participants on treatment for 96 weeks and on stable qw dosing for 24 weeks could be switched to an every other week (qow) dosing schedule. In the event of protocol-defined disease progression at any time during treatment, a participant could receive a dose increase from 1 to 3 mg/kg qw and, if necessary, a dose increase to 5 mg/kg qw with Safety Committee approval. Participants dosed qow who met dose-escalation criteria were reverted to qw dosing or escalated to 1 or 3 mg/kg qow.
干预措施: Sebelipase alfa (SBC-102) (Drug)
结局指标
主要结局
Percentage Of Participants In The Primary Efficacy Analysis Set (PES) Surviving To 12 Months Of Age
时间窗: Month 12
The primary efficacy endpoint was the percentage of participants (%) in the PES who survived to at least 12 months of age.
次要结局
- Change From Baseline To Months 12, 24, 36, 48, And 60 In Serum Transaminases (ALT And AST)(Baseline, Month 12, Month 24, Month 36, Month 48, and Month 60)
- Number Of Participants Achieving And Maintaining Transfusion-free Hemoglobin Normalization [TFHN](Baseline to Month 60)
- Percentage Of Participants Surviving Beyond 12 Months Of Age(Baseline to Month 18, Month 24, Month 36, Month 48, and Month 60)
- Median Age At Death(Baseline to Week 260)
- Change From Baseline To Months 12, 24, 36, 48, And 60 In Weight For Age (WFA) Percentiles(Baseline, Month 12, Month 24, Month 36, Month 48, and Month 60)
- Number Of Participants With Stunting, Wasting, Or Underweight(Baseline to Month 12, Month 24, Month 36, Month 48, and Month 60)
- Change From Baseline To Months 12, 24, 36, 48, And 60 In Serum Ferritin(Baseline, Month 12, Month 24, Month 36, Month 48, and Month 60)