Clinical Study In Infants With Rapidly Progressive Lysosomal Acid Lipase Deficiency

Alexion Pharmaceuticals

Status and phase: Terminated; Phase 2

Conditions: Lysosomal Acid Lipase Deficiency

Treatments: Drug: Sebelipase Alfa

Study type: Interventional

Funder types: Industry

Identifiers

NCT02193867

LAL-CL08

Details and patient eligibility

About

This was an open-label, repeat-dose, study of sebelipase alfa in infants with rapidly progressive lysosomal acid lipase deficiency (LAL-D). Eligible participants received once-weekly infusions of sebelipase alfa for up to 3 years.

Full description

Lysosomal acid lipase deficiency is a rare autosomal recessive lipid storage disorder that is caused by a marked decrease or complete absence of the LAL enzyme, leading to the accumulation of lipids, predominately cholesteryl esters and triglycerides, in various tissues and cell types. In the liver, accumulation of lipids in hepatocytes and macrophages leads to hepatomegaly, fibrosis, cirrhosis, liver dysfunction, and hepatic failure. In the small intestine, lipid-laden macrophage accumulation in the lamina propria leads to profound malabsorption.

Lysosomal acid lipase deficiency presenting in infancy is an extremely rare form of the disease characterized by profound malabsorption, growth failure, and hepatic failure that is usually fatal within the first 6 months of life.

Enrollment: 10 patients

Sex: All

Ages: Under 8 months old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Participant's parent or legal guardian (if applicable) consent to participation in the study

2. Confirmation of documented decreased LAL activity relative to the normal range of the lab performing the assay or confirmation of LAL-D diagnosis as determined by a Sponsor-approved central laboratory

3. Substantial clinical concerns, in the opinion of Investigator and Sponsor, of rapid disease progression requiring urgent medical intervention including, but not restricted to the following:

   • Marked abdominal distension and hepatomegaly
   • Failure to thrive
   • Disturbance of coagulation
   • Severe anemia
   • Sibling with rapidly progressive course of LAL-D

Exclusion criteria

1. Clinically important concurrent disease
2. Participant was > 8 months of age at the time of first dosing
3. Participant received an investigational medicinal product other than sebelipase alfa within 14 days prior to the first dose of sebelipase alfa in this study
4. Myeloablative preparation, or other systemic pre-transplant conditioning, for hematopoietic stem cell or liver transplantation
5. Previous hematopoietic stem cell or liver transplant
6. Known hypersensitivity to eggs

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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10 participants in 1 patient group

Open-Label Sebelipase Alfa

Experimental group

Description:

All participants initiated once weekly (qw) intravenous (IV) infusions with sebelipase alfa at a dose of 1 milligram/kilogram (mg/kg) qw. A participant who met protocol defined dose escalation criteria at a dose of 1 mg/kg qw could be considered for a dose escalation to 3 mg/kg qw. If a participant continued to meet dose escalation criteria after at least 4 infusions at a dose of 3 mg/kg qw, the participant could be considered for a further dose escalation to 5 mg/kg qw. Under country-specific provisions (United Kingdom only), participants could be considered for a further dose escalation to 7.5 mg/kg qw if a thorough case review indicated that a participant continued to have evidence of disease progression at a dose of 5 mg/kg qw. All dose escalations were contingent upon acceptable safety and tolerability of preceding infusions and were undertaken by mutual agreement of the Investigator and Sponsor and after approval by an independent safety committee.

Treatment:

Drug: Sebelipase Alfa