Trial in Children With Growth Failure Due to Early Onset Lysosomal Acid Lipase (LAL) Deficiency/Wolman Disease
Lysosomal Acid Lipase Deficiency
Drug: Sebelipase alfa (SBC-102)
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|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 Due to Lysosomal Acid Lipase Deficiency|
- 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) ] [ Designated as safety issue: No ]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.
- 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) ] [ Designated as safety issue: No ]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) ] [ Designated as safety issue: No ]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) ] [ Designated as safety issue: No ]
- Effect on Growth Parameters (Weight-for-age) [ Time Frame: from week 0 to data cut-off (27 to 164 weeks of treatment) ] [ Designated as safety issue: No ]Changes from baseline in percentiles for weight-for-age (WFA)
- Dichotomous Growth Status Indicators [ Time Frame: Month 12 of treatment ] [ Designated as safety issue: No ]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 ] [ Designated as safety issue: No ]Change from baseline for alanine aminotransferase (ALT) and aspartate aminotransferase (AST)
- Change in Serum Ferritin [ Time Frame: from week 0 to week 1 ] [ Designated as safety issue: No ]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) ] [ Designated as safety issue: No ]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.
|Study Start Date:||May 2011|
|Estimated Study Completion Date:||April 2018|
|Primary Completion Date:||August 2014 (Final data collection date for primary outcome measure)|
Experimental: Open-Label sebelipase alfa
All subjects received IV infusions of sebelipase alfa during the open-label treatment period. Subjects received a starting dose of 0.35 mg/kg once weekly (qw) and, after demonstrating acceptable safety and tolerability after at least 2 infusions at this dose, began receiving the per-protocol dose of 1 mg/kg qw. Thereafter, subjects were to continue receiving a dose of 1 mg/kg qw for the duration of the treatment period. However, in the event of disease progression (based on protocol-defined criteria) at any time during treatment with 1 mg/kg qw, an individual subject could receive a dose increase to 3 mg/kg qw and; if necessary, a subsequent dose increase to 5 mg/kg qw (after review and approval by a Safety Committee). Subjects receiving long-term treatment on a stable qw dose could be switched to an every other week (qow) dosing schedule at the same total dose (mg/kg) per infusion.
Drug: Sebelipase alfa (SBC-102)
Sebelipase alfa is a recombinant human lysosomal acid lipase (rhLAL). The investigational medicinal product is an enzyme replacement therapy intended for treatment of patients with LAL Deficiency. Dosing will occur once weekly for up to three years.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01371825
|United States, California|
|University of California, Irvine|
|Irvine, California, United States, 92697|
|United States, New York|
|North Shore Hospital Long Island Jewish Health System|
|Manhasset, New York, United States, 11030|
|Hopital Necker Enfants Malades|
|University of Mainz|
|New Delhi, India|
|Azienda Ospedaliera Universita di Padova|
|Riyadh, Saudi Arabia|
|National Taiwan University Hospital|
|St. Mary's Hospital, Central Manchester University Hospitals|
|Manchester, United Kingdom|