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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Synageva BioPharma Corp.
ClinicalTrials.gov Identifier:
NCT01488097
First received: November 26, 2011
Last updated: May 30, 2013
Last verified: May 2013
  Purpose

This is an extension study to the first clinical study of SBC-102 (sebelipase alfa) for the treatment of LAL Deficiency. It is an open label study in adult patients with liver dysfunction due to Lysosomal Acid Lipase (LAL) Deficiency. This study will assess the long-term safety, tolerability, and efficacy of SBC-102. The targeted number for this study is 9 evaluable subjects.


Condition Intervention Phase
Cholesterol Ester Storage Disease(CESD)
Lysosomal Acid Lipase Deficiency
Drug: SBC-102 (sebelipase alfa)
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Synageva BioPharma Corp.:

Primary Outcome Measures:
  • Long term safety of SBC-102 including incidence of adverse events [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
    The safety and tolerability of infusions of SBC-102 will be assessed by routine monitoring of patients for adverse events (AEs) and monitoring changes from baseline in physical examination findings, vital signs, clinical laboratory evaluations, immunogenicity tests and concomitant therapies.


Secondary Outcome Measures:
  • Changes in liver and spleen volume and fat content. [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Characterize the pharmacokinetics (e.g. AUC, Cmax, T1/2) of multiple doses of SBC-102 delivered by IV infusion. [ Time Frame: Pre-dose, 10, 15, 20, 40, 60 and 90 minutes during the infusion, the end of the infusion, and at 5, 10, 20, 30, 40, 60 and 120 minutes after completion of the infusion ] [ Designated as safety issue: No ]
  • Asses pharmacodynamics of SBC-102 on specified biomarkers, including change in transaminases, serum lipids and acute phase reactants. [ Time Frame: 3 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 9
Study Start Date: November 2011
Estimated Study Completion Date: January 2015
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cohort 1
Weekly IV infusions of Dose A of SBC-102 (sebelipase alfa) and bi-weekly IV infusions of Dose B or Dose C of SBC-102 (sebelipase alfa)
Drug: SBC-102 (sebelipase alfa)
Weekly IV infusions Dose A of SBC-102 (sebelipase alfa) and bi-weekly infusions of Dose B or Dose C of SBC-102 (sebelipase alfa)
Experimental: Cohort 2
Weekly IV infusions of Dose B of SBC-102 (sebelipase alfa) and bi-weekly infusions of Dose B or Dose C of SBC-102 (sebelipase alfa)
Drug: SBC-102 (sebelipase alfa)
Weekly IV infusions Dose B of SBC-102 (sebelipase alfa) and bi-weekly infusions of Dose B or Dose C of SBC-102 (sebelipase alfa)
Experimental: Cohort 3
Weekly IV infusions of Dose C of SBC-102 (sebelipase alfa) and bi-weekly infusions of Dose C of SBC-102 (sebelipase alfa)
Drug: SBC-102 (sebelipase alfa)
Weekly IV infusions Dose C of SBC-102 (sebelipase alfa) and bi-weekly infusions of Dose C of SBC-102 (sebelipase alfa)

Detailed Description:

Cholesteryl Ester Storage Disease (CESD) is the late onset phenotype for Lysosomal Acid Lipase (LAL) Deficiency, a Lysosomal Storage Disorder, which also has an early onset phenotype known as Wolman Disease 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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subject received all 4 scheduled doses of SBC-102 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 liver function or lipid panel tests
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01488097

Locations
United States, New York
Mount Sinai School of Medicine
New York, New York, United States, 10029
Czech Republic
1st Faculty of Medicine Charles University
Prague, Czech Republic
France
Hôpital Necker-Enfants Malades
Paris, France
United Kingdom
Addenbrooke's Hospital
Cambridge, United Kingdom
Salford Royal
Salford, United Kingdom
Sponsors and Collaborators
Synageva BioPharma Corp.
  More Information

Publications:
Responsible Party: Synageva BioPharma Corp.
ClinicalTrials.gov Identifier: NCT01488097     History of Changes
Other Study ID Numbers: LAL-CL04
Study First Received: November 26, 2011
Last Updated: May 30, 2013
Health Authority: United States: Food and Drug Administration
United Kingdom: Medicines and Healthcare Products Regulatory Agency
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Czech Republic: State Institute for Drug Control

Keywords provided by Synageva BioPharma Corp.:
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 Deficiency
Wolman disease

Additional relevant MeSH terms:
Cholesterol Ester Storage Disease
Wolman Disease
Metabolic Diseases
Lipidoses
Lipid Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Lysosomal Storage Diseases
Lipid Metabolism Disorders
Infant, Newborn, Diseases

ClinicalTrials.gov processed this record on April 16, 2014