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OpenTrials
Completed

NCT Number: NCT01371825

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

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.

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Key information

Conditions

Lysosomal Acid Lipase Deficiency Alcohol-Induced Disorders Alcohol-Related Disorders Brain Diseases Brain Diseases, Metabolic Brain Diseases, Metabolic, Inborn Central Nervous System Diseases Chanarin-Dorfman Syndrome Chemically-Induced Disorders Cholesterol Ester Storage Disease Cirrhosis, Cryptogenic Congenital, Hereditary, and Neonatal Diseases and Abnormalities Digestive System Diseases Fatty Liver Genetic Diseases, Inborn Hemic and Lymphatic Diseases Histiocytosis Histiocytosis, Non-Langerhans-Cell Infant, Newborn, Diseases Lipid Metabolism Disorders Lipid Metabolism, Inborn Errors Lipidoses Liver Diseases Liver Diseases, Alcoholic Lymphatic Diseases Lysosomal Storage Diseases Lysosomal Storage Diseases, Nervous System Metabolic Diseases Metabolism, Inborn Errors Nervous System Diseases Niemann-Pick Diseases Non-alcoholic Fatty Liver Disease Nutritional and Metabolic Diseases Sphingolipidoses Substance-Related Disorders Wolman Disease

Age range

Up to 24 month

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2 / Phase 3

Primary location

Cairo, Egypt

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Sebelipase alfa (SBC-102)

Drug

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.

Primary outcomes

  1. Percentage Of Participants In The Primary Efficacy Analysis Set (PES) Surviving To 12 Months Of Age

    Time frame: Month 12

    The primary efficacy endpoint was the percentage of participants (%) in the PES who survived to at least 12 months of age.

Secondary outcomes

  1. Percentage Of Participants Surviving Beyond 12 Months Of Age

    Time frame: Baseline to Month 18, Month 24, Month 36, Month 48, and Month 60

    The percentage of participants in the PES who survived to at least 18 months of age.

  2. Median Age At Death

    Time frame: Baseline to Week 260

    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.

  3. Change From Baseline To Months 12, 24, 36, 48, And 60 In Weight For Age (WFA) Percentiles

    Time frame: Baseline, Month 12, Month 24, Month 36, Month 48, and Month 60

    Baseline is defined as the last measurement prior to the first infusion of sebelipase alfa.

  4. Number Of Participants With Stunting, Wasting, Or Underweight

    Time frame: Baseline to Month 12, Month 24, Month 36, Month 48, and Month 60

    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.

  5. Change From Baseline To Months 12, 24, 36, 48, And 60 In Serum Transaminases (ALT And AST)

    Time frame: Baseline, Month 12, Month 24, Month 36, Month 48, and Month 60

    Change from Baseline to Months 12, 24, 36, 48, and 60 for alanine aminotransferase (ALT) and aspartate aminotransferase (AST).

  6. Change From Baseline To Months 12, 24, 36, 48, And 60 In Serum Ferritin

    Time frame: Baseline, Month 12, Month 24, Month 36, Month 48, and Month 60

    The median change in serum ferritin from Baseline to Months 12, 24, 36, 48, and 60 is presented.

  7. Number Of Participants Achieving And Maintaining Transfusion-free Hemoglobin Normalization [TFHN]

    Time frame: Baseline to Month 60

    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.

Sponsors and collaborators

Lead sponsor

Alexion Pharmaceuticals, Inc.

Industry

Registry information

Official study 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

Important dates

Study start
2011
Primary completion
2018
Study completion
2018
First posted
Jun 13, 2011
Registry last updated
Jan 30, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

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This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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