SurVival of Lysosomal Acid Lipase Deficiency (LAL-D) Infants Treated With SebelipAse aLfa (VITAL)

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: NCT01371825
Recruitment Status : Active, not recruiting
First Posted : June 13, 2011
Results First Posted : April 18, 2016
Last Update Posted : November 14, 2017
Information provided by (Responsible Party):
Alexion Pharmaceuticals

Brief Summary:
This is an open-label, repeat-dose, intra-subject dose escalation study of SBC-102 (USAN: sebelipase alfa) in children with growth failure due to LAL Deficiency. Eligible subjects will receive once-weekly (qw) infusions of sebelipase alfa for up to 5 years

Condition or disease Intervention/treatment Phase
Lysosomal Acid Lipase Deficiency Wolman Disease Drug: Sebelipase alfa (SBC-102) Phase 2 Phase 3

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 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 two 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. There is currently no approved therapy for the treatment of LAL Deficiency.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 9 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Study Start Date : May 2011
Actual Primary Completion Date : August 2014
Estimated Study Completion Date : April 2018

Arm Intervention/treatment
Experimental: Open-Label sebelipase alfa
All subjects received IV infusions of sebelipase alfa during the open-label treatment period. Subjects received a starting dose of 0.35 mg/kg once weekly (qw) and, after demonstrating acceptable safety and tolerability after at least 2 infusions at this dose, began receiving the per-protocol dose of 1 mg/kg qw. Thereafter, subjects were to continue receiving a dose of 1 mg/kg qw for the duration of the treatment period. However, in the event of disease progression (based on protocol-defined criteria) at any time during treatment with 1 mg/kg qw, an individual subject could receive a dose increase to 3 mg/kg qw and; if necessary, a subsequent dose increase to 5 mg/kg qw (after review and approval by a Safety Committee). Subjects receiving long-term treatment on a stable qw dose could be switched to an every other week (qow) dosing schedule at the same total dose (mg/kg) per infusion.
Drug: Sebelipase alfa (SBC-102)
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 LAL Deficiency. Dosing will occur once weekly for up to three years.

Primary Outcome Measures :
  1. Percentage of Subjects in the PES Surviving to 12 Months of Age [ Time Frame: From week 0 to data cut-off (27 to 164 weeks of treatment) ]
    The primary efficacy endpoint was the percentage of subjects (%) in the Primary Efficacy Analysis Set (PES) who survived to at least 12 months of age.

Secondary Outcome Measures :
  1. Percentage of Subjects in the PES Surviving at 18 Months of Age [ Time Frame: from week 0 to data cut-off (27 to 164 weeks of treatment) ]
    The percentage of subjects in the Primary Efficacy Analysis Set (PES) who survived to at least 18 months of age.

  2. Percentage of Subjects in the PES Surviving at 24 Months of Age [ Time Frame: from week 0 to data cut-off (27 to 164 weeks of treatment) ]
    The percentage of subjects in the Primary Efficacy Analysis Set (PES) who survived to at least 24 months of age.

  3. Median Age at Death [ Time Frame: from week 0 to data cut-off (27 to 164 weeks of treatment) ]
  4. Effect on Growth Parameters (Weight-for-age) [ Time Frame: from week 0 to data cut-off (27 to 164 weeks of treatment) ]
    Changes from baseline in percentiles for weight-for-age (WFA)

  5. Dichotomous Growth Status Indicators [ Time Frame: Month 12 of treatment ]
    The percentages of subjects meeting criteria for each dichotomous indicator of under nutrition, i.e., underweight (at least 2 SD below median for weight-for-age [WFA]), wasting (at least 2 SD below median for weight-for-length or -height [WFL/WFH]), and stunting (at least 2 SD below median for length- or height-for-age [LFA/HFA])

  6. Changes in Serum Transaminases [ Time Frame: from week 0 to weeks 1 and 4 ]
    Change from baseline for alanine aminotransferase (ALT) and aspartate aminotransferase (AST)

  7. Change in Serum Ferritin [ Time Frame: from week 0 to week 1 ]
    Change from baseline in serum ferritin

  8. Percentage of Subjects Achieving Transfusion-free Hemoglobin Normalization [ Time Frame: from week 0 to data cut-off (27 to 164 weeks of treatment) ]
    The percentage of subjects achieving transfusion-free hemoglobin normalization (TFHN) of ≥ 4 weeks at any time during the study (also referred to as short-term TFHN), and the percentage of subjects who maintained TFHN for ≥ 13 weeks beginning at Week 6 (also referred to as sustained early TFHN). A subject was considered to have achieved short-term TFHN if the/she had two post-baseline measurements of hemoglobin, obtained at least 4 weeks apart, that were above the age-adjusted lower limit of normal (LLN), and had no additional hemoglobin measurements below LLN during this minimum 4-week period and no transfusions administered during the minimum 4-week period or for 2 weeks prior to the start of this period.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Ages Eligible for Study:   up to 24 Months   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Subject's parent or legal guardian provides 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 lab 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.
  • Has received an investigational product other than sebelipase alfa within 14 days prior to the first dose.
  • Subject is 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.

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): NCT01371825

United States, California
University of California, Irvine
Irvine, California, United States, 92697
United States, New York
North Shore Hospital Long Island Jewish Health System
Manhasset, New York, United States, 11030
Ain Shams University Pediatrics Hospital
Cairo, Egypt
CHU Grenoble Alpes
Grenoble, France, 38700
Hopital Necker Enfants Malades
Paris, France
Children's University Hospital, Temple Street
Dublin, Ireland
Saudi Arabia
Dept of Medical Genetics, King Faisal Specialist Hospital
Riyadh, Saudi Arabia
United Kingdom
Evalina Children's Hospital
London, United Kingdom
St. Mary's Hospital, Central Manchester University Hospitals
Manchester, United Kingdom
Sponsors and Collaborators
Alexion Pharmaceuticals

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: Alexion Pharmaceuticals Identifier: NCT01371825     History of Changes
Other Study ID Numbers: LAL-CL03
First Posted: June 13, 2011    Key Record Dates
Results First Posted: April 18, 2016
Last Update Posted: November 14, 2017
Last Verified: October 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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

Additional relevant MeSH terms:
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