Clinical Trial in Infants With Rapidly Progressive Lysosomal Acid Lipase Deficiency

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ClinicalTrials.gov Identifier: NCT02193867

Recruitment Status : Active, not recruiting

First Posted : July 18, 2014

Last Update Posted : September 6, 2017

Sponsor:

Information provided by (Responsible Party):

Alexion Pharmaceuticals

Study Description

Brief Summary:

This is an open-label, repeat-dose, study of sebelipase alfa in infants with rapidly progressive LAL Deficiency. Eligible subjects will receive once-weekly infusions of sebelipase alfa for up to 3 years.

Condition or disease	Intervention/treatment	Phase
Lysosomal Acid Lipase Deficiency	Drug: sebelipase alfa	Phase 2

Detailed Description:

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 the LAL enzyme, leading to the accumulation of these 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. In the small intestine, lipid-laden macrophage accumulation in the lamina propria leads to profound malabsorption.

LAL Deficiency presenting in infancy is extremely rare form of LAL Deficiency. It is characterized by profound malabsorption, growth failure, and hepatic failure, and is usually fatal in the first 6 months of life. There is currently no safe or effective therapy for the treatment of LAL Deficiency.

Study Design


Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	10 participants
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	A Phase 2, Open Label, Multicenter Study to Evaluate the Safety, Tolerability, Efficacy, and Pharmacokinetics of Sebelipase Alfa in Infants With Rapidly Progressive Lysosomal Acid Lipase Deficiency
Actual Study Start Date :	June 2014
Estimated Primary Completion Date :	April 2018
Estimated Study Completion Date :	April 2018

Resource links provided by the National Library of Medicine

Genetics Home Reference related topics: Lysosomal acid lipase deficiency

Drug Information available for: Sebelipase alfa

Genetic and Rare Diseases Information Center resources: Visceral Steatosis Frontotemporal Dementia Frontotemporal Dementia, Ubiquitin-positive Pick's Disease Primary Progressive Aphasia Semantic Dementia Niemann-Pick Disease Niemann-Pick Disease Type A Wolman Disease Cholesteryl Ester Storage Disease Lysosomal Acid Lipase Deficiency Chanarin-Dorfman Syndrome

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Experimental: Cohort 1 Weekly IV infusions of sebelipase alfa	Drug: sebelipase alfa 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 Lysosomal Acid Lipase Deficiency. Dosing will occur once weekly for up to three years.

Outcome Measures

Primary Outcome Measures :

Long-term safety [ Time Frame: Up to 3 years ]
- Incidence of AEs and SAEs
- Changes from baseline clinical laboratory tests
- Changes in vitals
- Physical examination findings
- Use of concomitant medications

Secondary Outcome Measures :

Survival at 12 months of age [ Time Frame: 12 months ]
Survival beyond 12 months of age [ Time Frame: Up to 3 years ]
Growth [ Time Frame: Up to 3 years ]
- changes from baseline in percentiles and/or z-scores for weight for age (WFA), weight for length (WFL)/weight for height(WFH), and length for age (LFA)/height for age (HFA)
- growth status indicators of underweight, wasting, and stunting
- changes from baseline in z scores for head circumference-for-age (HCFA) and mid-upper arm circumference-for-age (MUACFA)
Hematological parameters [ Time Frame: Up to 3 years ]
- Changes from baseline in aspartate aminotransferase (AST) and ALT
- Normalization of hemoglobin levels without requirement for blood transfusion
- Change from baseline in serum ferritin.
Characterize the PK of sebelipase alfa [ Time Frame: Up to 3 years ]
Cmax of sebelipase alfa

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:	up to 8 Months (Child)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Subject's parent or legal guardian (if applicable) consents to participation in the study.
Confirmation of LAL Deficiency diagnosis as determined by a Sponsor approved central laboratory.
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 Deficiency

Exclusion Criteria:

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

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02193867

Locations


United States, California

Irvine, California, United States
Italy

Naples, Italy
United Kingdom

Birmingham, United Kingdom

Manchester, United Kingdom

Sponsors and Collaborators

Alexion Pharmaceuticals

Investigators


Study Director:	Mark Friedman, MD	Alexion Pharmaceuticals

More Information

Publications:

Balwani M, Breen C, Enns GM, Deegan PB, Honzík T, Jones S, Kane JP, Malinova V, Sharma R, Stock EO, Valayannopoulos V, Wraith JE, Burg J, Eckert S, Schneider E, Quinn AG. Clinical effect and safety profile of recombinant human lysosomal acid lipase in patients with cholesteryl ester storage disease. Hepatology. 2013 Sep;58(3):950-7. doi: 10.1002/hep.26289. Epub 2013 Mar 28.


Responsible Party:	Alexion Pharmaceuticals
ClinicalTrials.gov Identifier:	NCT02193867 History of Changes
Other Study ID Numbers:	LAL-CL08
First Posted:	July 18, 2014 Key Record Dates
Last Update Posted:	September 6, 2017
Last Verified:	September 2017

Keywords provided by Alexion Pharmaceuticals:


LIPA Wolman Disease Wolman Phenotype Acid Lipase Deficiency Acid Cholesteryl Hydrolase Acid Lipase Disease Deficiency, type 2 Cholesteryl Ester Storage Disease (CESD) Cholesteryl Ester Hydrolase Deficiency Early Onset Lysosomal Acid Lipase Deficiency (Wolman Disease) LAL Deficiency	Late Onset Lysosomal Acid Lipase Deficiency (CESD) Wolman Disease (early onset LAL Deficiency) Related Disorders: Non-alcoholic Fatty Liver Disease (NAFLD) Non-alcoholic Steatohepatitis (NASH) Alcoholic Liver Disease Cryptogenic Cirrhosis Niemann-Pick Disease (NPD) Type C Chanarin Dorfman Syndrome

Additional relevant MeSH terms:


Wolman Disease Cholesterol Ester Storage Disease Lipidoses Lipid Metabolism, Inborn Errors Metabolism, Inborn Errors	Genetic Diseases, Inborn Lysosomal Storage Diseases Infant, Newborn, Diseases Lipid Metabolism Disorders Metabolic Diseases

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