Safety, Tolerability, Efficacy, Pharmacokinetics, and Pharmacodynamics of Sebelipase Alfa in Children With Growth Failure Due to Lysosomal Acid Lipase Deficiency

Lysosomal Acid Lipase Deficiency Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01371825
• Other study ID #: LAL-CL03
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: May 4, 2011
• Est. completion date: January 3, 2018

Study information

• Verified date: January 2019
• Source: Alexion Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 9
• Est. completion date: January 3, 2018
• Est. primary completion date: January 3, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 24 Months

Eligibility

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.

Related Conditions & MeSH terms

• Failure to Thrive
• Lysosomal Acid Lipase Deficiency
• Wolman Disease

Intervention

Drug:
• Sebelipase alfa (SBC-102)
Sebelipase alfa is a recombinant human lysosomal acid lipase enzyme. The investigational medicinal product is an enzyme replacement therapy intended for treatment of participants with LAL Deficiency. Dosing occurred qw for up to 5 years.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Alexion Pharmaceuticals

Countries where clinical trial is conducted

United States,  Egypt,  France,  Ireland,  United Kingdom, 

References & Publications (1)

Jones SA, Rojas-Caro S, Quinn AG, Friedman M, Marulkar S, Ezgu F, Zaki O, Gargus JJ, Hughes J, Plantaz D, Vara R, Eckert S, Arnoux JB, Brassier A, Le Quan Sang KH, Valayannopoulos V. Survival in infants treated with sebelipase Alfa for lysosomal acid lipase deficiency: an open-label, multicenter, dose-escalation study. Orphanet J Rare Dis. 2017 Feb 8;12(1):25. doi: 10.1186/s13023-017-0587-3. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage Of Participants In The Primary Efficacy Analysis Set (PES) Surviving To 12 Months Of Age	The primary efficacy endpoint was the percentage of participants (%) in the PES who survived to at least 12 months of age.	Month 12
Secondary	Percentage Of Participants Surviving Beyond 12 Months Of Age	The percentage of participants in the PES who survived to at least 18 months of age.	Baseline to Month 18, Month 24, Month 36, Month 48, and Month 60
Secondary	Median Age At Death	Participants in the PES who died during the study, including 3 participants who died after having received between 1 and 4 infusions of sebelipase alfa and 1 participant who died after approximately 40 weeks on treatment.	Baseline to Week 260
Secondary	Change From Baseline To Months 12, 24, 36, 48, And 60 In Weight For Age (WFA) Percentiles	Baseline is defined as the last measurement prior to the first infusion of sebelipase alfa.	Baseline, Month 12, Month 24, Month 36, Month 48, and Month 60
Secondary	Number Of Participants With Stunting, Wasting, Or Underweight	The number of participants who met criteria for the following dichotomous indicators of under nutrition were reported. These indicators included the following: Stunting was defined as at least 2 standard deviations below the median for length-for-age/height-for-age; Wasting was defined as wasting at least 2 standard deviations below the median for weight-for-length/weight-for-height; and; Underweight was defined as at least 2 standard deviations below the median for WFA.	Baseline to Month 12, Month 24, Month 36, Month 48, and Month 60
Secondary	Change From Baseline To Months 12, 24, 36, 48, And 60 In Serum Transaminases (ALT And AST)	Change from Baseline to Months 12, 24, 36, 48, and 60 for alanine aminotransferase (ALT) and aspartate aminotransferase (AST).	Baseline, Month 12, Month 24, Month 36, Month 48, and Month 60
Secondary	Change From Baseline To Months 12, 24, 36, 48, And 60 In Serum Ferritin	The median change in serum ferritin from Baseline to Months 12, 24, 36, 48, and 60 is presented.	Baseline, Month 12, Month 24, Month 36, Month 48, and Month 60
Secondary	Number Of Participants Achieving And Maintaining Transfusion-free Hemoglobin Normalization [TFHN]	The number of participants achieving and maintaining TFHN are presented.; For TFHN to be achieved, the participant must a) have had 2 post-baseline measurements of hemoglobin at least 4 weeks apart that were both above the age-adjusted lower limit of normal; b) have had no known additional measurements of hemoglobin that were below the age-adjusted lower limit of normal during the (minimum) 4-week period; and c) have had no transfusions during the (minimum) 4-week period, and also no transfusions for 2 weeks prior to the first hemoglobin measurement in the (minimum) 4-week period.; For TFHN to be maintained, the participant must have been transfusion-free beginning at Week 6 and had all hemoglobin assessments above the lower limit of normal beginning in Week 8 and lasting at least 13 weeks.	Baseline to Month 60