Clinical Trial: SurVival of Lysosomal Acid Lipase Deficiency (LAL-D) Infants Treated With SebelipAse aLfa

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: 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 Du

Brief Summary: This is an open-label, repeat-dose, intra-subject dose escalation study of SBC-102 (USAN: sebelipase alfa) in children with growth failure due to LAL Deficiency. Eligible subjects will receive once-weekly (qw) infusions of sebelipase alfa for up to 5 years

Detailed Summary:

Lysosomal Acid Lipase (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 two 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. There is currently no approved therapy for the treatment of LAL Deficiency.


Sponsor: Alexion Pharmaceuticals

Current Primary Outcome: Percentage of Subjects in the PES Surviving to 12 Months of Age [ Time Frame: From week 0 to data cut-off (27 to 164 weeks of treatment) ]

The primary efficacy endpoint was the percentage of subjects (%) in the Primary Efficacy Analysis Set (PES) who survived to at least 12 months of age.


Original Primary Outcome: To evaluate treatment emergent Adverse Events (AEs). [ Time Frame: 135 Days ]

The safety and tolerability of weekly infusions of SBC-102 will be assessed by routine monitoring of patients for adverse events (AEs) and monitoring changes from baseline in physical examination findings, vital signs, clinical laboratory evaluations, immunogenicity tests and concomitant therapies.


Current Secondary Outcome:

  • Percentage of Subjects in the PES Surviving at 18 Months of Age [ Time Frame: from week 0 to data cut-off (27 to 164 weeks of treatment) ]
    The percentage of subjects in the Primary Efficacy Analysis Set (PES) who survived to at least 18 months of age.
  • Percentage of Subjects in the PES Surviving at 24 Months of Age [ Time Frame: from week 0 to data cut-off (27 to 164 weeks of treatment) ]
    The percentage of subjects in the Primary Efficacy Analysis Set (PES) who survived to at least 24 months of age.
  • Median Age at Death [ Time Frame: from week 0 to data cut-off (27 to 164 weeks of treatment) ]
  • Effect on Growth Parameters (Weight-for-age) [ Time Frame: from week 0 to data cut-off (27 to 164 weeks of treatment) ]
    Changes from baseline in percentiles for weight-for-age (WFA)
  • Dichotomous Growth Status Indicators [ Time Frame: Month 12 of treatment ]
    The percentages of subjects meeting criteria for each dichotomous indicator of under nutrition, i.e., underweight (at least 2 SD below median for weight-for-age [WFA]), wasting (at least 2 SD below median for weight-for-length or -height [WFL/WFH]), and stunting (at least 2 SD below median for length- or height-for-age [LFA/HFA])
  • Changes in Serum Transaminases [ Time Frame: from week 0 to weeks 1 and 4 ]
    Change from baseline for alanine aminotransferase (ALT) and aspartate aminotransferase (AST)
  • Change in Serum Ferritin [ Time Frame: from week 0 to week 1 ]
    Change from baseline in serum ferritin
  • Percentage of Subjects Achieving Transfusion-free Hemoglobin Normalization [ Time Frame: from week 0 to data cut-off (27 to 164 weeks of treatment) ]
    The percentage of subjects achieving transfusion-free hemoglobin normalization (TFHN) of ≥ 4 weeks at any time during the study (also referred to as short-term TFHN), and the percentage of subjects who maintained TFHN for ≥ 13 weeks beginning at Week 6 (also referred to as sustained early TFHN). A subject was considered to have achieved short-term TFHN if the/she had two post-baseline measurements of hemoglobin, obtained at least 4 weeks apart, that were above the age-adjusted lower limit of normal (LLN), and had no additional hemoglobin measurements below LLN during this minimum 4-week period and no transfusions administered during the minimum 4-week period or for 2 weeks prior to the start of this period.


Original Secondary Outcome: To determine the effect of SBC-102 on growth. [ Time Frame: 135 Days ]

Changes in weight and length over the course of the trial will be evaluated and compared to standard growth curves.


Information By: Alexion Pharmaceuticals

Dates:
Date Received: June 9, 2011
Date Started: May 2011
Date Completion: April 2018
Last Updated: August 4, 2016
Last Verified: August 2016