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Extension Study to Evaluate the Long-Term Safety, Tolerability, and Efficacy of SBC-102 (Sebelipase Alfa) in Adult Subjects With Lysosomal Acid Lipase Deficiency

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ClinicalTrials.gov Identifier: NCT01488097
Recruitment Status : Completed
First Posted : December 8, 2011
Results First Posted : May 9, 2016
Last Update Posted : July 20, 2018
Sponsor:
Information provided by (Responsible Party):
Alexion Pharmaceuticals

Brief Summary:
This was an extension study to Study LAL-CL01 (NCT01307098). The primary objective of the study was to evaluate the long-term safety and tolerability of sebelipase alfa in participants with liver dysfunction due to lysosomal acid lipase (LAL) deficiency.

Condition or disease Intervention/treatment Phase
Cholesterol Ester Storage Disease (CESD) Lysosomal Acid Lipase Deficiency LAL-Deficiency Drug: sebelipase alfa Phase 2

Detailed Description:

Participants who successfully received all 4 doses of sebelipase alfa in Study LAL-CL01 and opted to continue treatment in the extension study underwent screening assessments to determine study eligibility. Eligible participants initiated treatment in the extension study at least 4 weeks after their last dose of sebelipase alfa in Study LAL-CL01. This extension study consisted of a treatment period of up to 5 years, and a follow-up period of approximately 30 days after the last dose of sebelipase alfa.

Cholesteryl ester storage disease (CESD) is the late onset phenotype for LAL deficiency, a lysosomal storage disorder, which also has an early onset phenotype that primarily affects infants. CESD can present in childhood but often goes unrecognized until adulthood when the underlying pathology is advanced. Many of the signs and symptoms are common to patients with other liver conditions.

CESD is an autosomal recessive genetic condition and is characterized by hepatomegaly, persistently abnormal liver function tests (LFTs) and type II hyperlipidemia. Splenomegaly and evidence of mild hypersplenism may affect some patients. Untreated, CESD may lead to fibrosis, cirrhosis, liver failure and death.


Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 8 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open Label Multicenter Extension Study to Evaluate the Long-Term Safety, Tolerability, and Efficacy of SBC-102 in Adult Subjects With Liver Dysfunction Due to Lysosomal Acid Lipase Deficiency Who Previously Received Treatment in Study LAL-CL01
Actual Study Start Date : December 12, 2011
Actual Primary Completion Date : June 21, 2017
Actual Study Completion Date : June 21, 2017


Arm Intervention/treatment
Experimental: Open-Label Sebelipase Alfa
Participants were administered sebelipase alfa once weekly (qw) as an intravenous (IV) infusion at the same dose received in Study LAL-CL01 (0.35, 1, or 3 milligrams per kilogram [mg/kg]) for 4 weeks. After the initial 4 qw doses, participants transitioned to dosing every other week (qow) at either 1 mg/kg (participants who initiated treatment at 0.35 or 1 mg/kg qw) or 3 mg/kg (participants who initiated dosing at 3 mg/kg qw). Subsequent modifications to the dose and dosing frequency were permitted for individual participants based on observed safety, tolerability, and clinical response to treatment. Participants could continue to receive treatment with sebelipase alfa for up to 5 years.
Drug: sebelipase alfa
Sebelipase alfa is a recombinant human lysosomal acid lipase.
Other Names:
  • SBC-102
  • Kanuma®




Primary Outcome Measures :
  1. Number Of Participants Reporting TEAEs And IARs [ Time Frame: From after first dose administration post-Baseline through EOS during study LAL-CL04 ]
    Safety and tolerability of sebelipase alfa was primarily assessed by monitoring the number of participants reporting treatment-emergent adverse events (TEAEs), including serious adverse events, and infusion-associated reactions (IARs). The number of participants who discontinued from the study due to a TEAE is also presented. An IAR was defined as any adverse event that occurred during the 2-hour infusion or within 4 hours after the end of the infusion and was assessed by the investigator as at least possibly related to study drug. A summary of serious and all other non-serious adverse events regardless of causality is located in the Reported Adverse Events module. TEAEs that occurred after the first dose administration at Week 1 through the End of Study (EOS) are presented. End of study was 30 days (+ 7 days) after the last dose of study drug (at Week 260).


Secondary Outcome Measures :
  1. Changes From Baseline In ALT And AST [ Time Frame: Baseline, Week 12, Week 24, Week 52, Week 104, Week 156, Week 208, Week 260, and EOS ]
    Changes from Baseline to Week 12, Week 24, Week 52, Week 104, Week 156, Week 208, Week 260, and EOS for alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Baseline values were defined as the last measurement prior to the first infusion of sebelipase alfa in Study LAL-CL04.

  2. Changes From Baseline In Liver Volume [ Time Frame: Baseline, Week 10 or 12, Week 24, Week 52, Week 104, Week 156, Week 208, Week 260, and EOS ]
    Changes in liver volume from Baseline to Week 10 or 12, Week 24, Week 52, Week 104, Week 156, Week 208, Week 260, and EOS was assessed by magnetic resonance imaging (MRI). Baseline values were defined as the last measurement prior to the first infusion of sebelipase alfa in Study LAL-CL04. Liver volume was expressed as multiples of normal (MN), where normal is defined as 2.5% of body weight.

  3. Changes From Baseline In Liver Fat Content [ Time Frame: Baseline, Week 10 or 12, Week 24, Week 52, Week 104, Week 156, Week 208, and Week 260 ]
    Changes in liver fat content from Baseline to Week 10 or 12, Week 24, Week 52, Week 104, Week 156, Week 208, and Week 260, as assessed by multi-echo gradient-echo MRI. Baseline values were defined as the last measurement prior to the first infusion of sebelipase alfa in Study LAL-CL04.

  4. Changes From Baseline In GGT And ALP [ Time Frame: Baseline, Week 12, Week 24, Week 52, Week 104, Week 156, Week 208, Week 260, and EOS ]
    Changes from Baseline to Week 12, Week 24, Week 52, Week 104, Week 156, Week 208, Week 260, and EOS for gamma glutamyltransferase (GGT) and alkaline phosphatase (ALP). Baseline values were defined as the last measurement prior to the first infusion of sebelipase alfa in Study LAL-CL04.

  5. Changes From Baseline In Serum Lipids [ Time Frame: Baseline, Week 10 or 12, Week 24, Week 52, Week 104, Week 156, Week 208, Week 260, and EOS ]
    Lipid changes from Baseline to Week 10 or 12, Week 24, Week 52, Week 104, Week 156, Week 208, Week 260, and EOS were measured in serum for total cholesterol (Total-C), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), and triglycerides (TG). Baseline values were defined as the last measurement prior to the first infusion of sebelipase alfa in Study LAL-CL04.

  6. Changes From Baseline In Serum Ferritin [ Time Frame: Baseline, Week 12, Week 24, Week 52, Week 104, Week 156, Week 208, Week 260, and EOS ]
    Changes from Baseline to Week 12, Week 24, Week 52, Week 104, Week 156, Week 208, Week 260, and EOS for serum ferritin. Baseline values were defined as the last measurement prior to the first infusion of sebelipase alfa in Study LAL-CL04.

  7. Changes From Baseline In Hs-CRP [ Time Frame: Baseline, Week 12, Week 24, Week 52, Week 104, Week 156, Week 208, Week 260, and EOS ]
    Changes from Baseline to Week 12, Week 24, Week 52, Week 104, Week 156, Week 208, Week 260, and EOS for high sensitivity C-reactive protein (hs-CRP). Baseline values were defined as the last measurement prior to the first infusion of sebelipase alfa in Study LAL-CL04.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Participant received all 4 scheduled doses of sebelipase alfa in Study LAL-CL01 with no life-threatening or unmanageable study drug toxicity.

Exclusion Criteria:

  • Clinically significant concurrent disease, serious inter-current illness, concomitant medications or other extenuating circumstances
  • Clinically significant abnormal values on laboratory screening tests, other than LFTs or lipid panel tests

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): NCT01488097


Locations
United States, California
Eureka, California, United States, 95501-320
Sacramento, California, United States, 95817
San Francisco, California, United States, 94143
United States, Minnesota
Minneapolis, Minnesota, United States, 55455
United States, New York
New York, New York, United States, 10029
Canada, Ontario
Sudbury, Ontario, Canada
Czechia
Prague, Czechia
France
Paris, France
United Kingdom
Leeds, United Kingdom
Salford, United Kingdom
Sponsors and Collaborators
Alexion Pharmaceuticals
  Study Documents (Full-Text)

Documents provided by Alexion Pharmaceuticals:
Study Protocol  [PDF] January 5, 2016
Statistical Analysis Plan  [PDF] May 16, 2017


Additional Information:
Publications of Results:
Responsible Party: Alexion Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01488097     History of Changes
Other Study ID Numbers: LAL-CL04
First Posted: December 8, 2011    Key Record Dates
Results First Posted: May 9, 2016
Last Update Posted: July 20, 2018
Last Verified: June 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Alexion Pharmaceuticals:
Enzyme replacement therapy (ERT)
Lysosomal storage disease
Late onset lysosomal acid lipase (LAL) deficiency
Acid cholesteryl ester hydrolase deficiency, type 2
Acid lipase disease
Cholesterol ester hydrolase deficiency
LAL deficiency
LIPA enzyme deficiency

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