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Clinical Trial in Infants With Rapidly Progressive Lysosomal Acid Lipase Deficiency

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02193867
Recruitment Status : Active, not recruiting
First Posted : July 18, 2014
Last Update Posted : September 6, 2017
Information provided by (Responsible Party):
Alexion Pharmaceuticals

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.

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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

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.

Primary Outcome Measures :
  1. 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 :
  1. Survival at 12 months of age [ Time Frame: 12 months ]
  2. Survival beyond 12 months of age [ Time Frame: Up to 3 years ]
  3. 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)

  4. 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.

  5. Characterize the PK of sebelipase alfa [ Time Frame: Up to 3 years ]
    Cmax of sebelipase alfa

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

Inclusion Criteria:

  1. Subject's parent or legal guardian (if applicable) consents to participation in the study.
  2. Confirmation of LAL Deficiency 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 Deficiency

Exclusion Criteria:

  1. Clinically important concurrent disease
  2. Subject will be > 8 months of age at the time of first dosing.
  3. 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.
  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.

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 identifier (NCT number): NCT02193867

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United States, California
Irvine, California, United States
Naples, Italy
United Kingdom
Birmingham, United Kingdom
Manchester, United Kingdom
Sponsors and Collaborators
Alexion Pharmaceuticals
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Study Director: Mark Friedman, MD Alexion Pharmaceuticals

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Responsible Party: Alexion Pharmaceuticals 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:
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:
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Wolman Disease
Cholesterol Ester Storage Disease
Lipid Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Lysosomal Storage Diseases
Infant, Newborn, Diseases
Lipid Metabolism Disorders
Metabolic Diseases