Overview

This trial is active, not recruiting.

Conditions cholesterol ester storage disease (cesd), lysosomal acid lipase deficiency
Treatments sbc-102 [sebelipase alfa] (1 mg/kg), placebo
Phase phase 3
Sponsor Alexion Pharmaceuticals
Start date January 2013
End date July 2014
Trial size 66 participants
Trial identifier NCT01757184, LAL-CL02

Summary

This Phase 3 study will evaluate the efficacy and safety of 1 mg/kg IV infusions of SBC-102 (sebelipase alfa) administered every other week in patients with late onset lysosomal acid lipase (LAL) deficiency (cholesteryl ester storage disease).

Late onset LAL Deficiency is an underappreciated cause of cirrhosis, liver failure and dyslipidemia. There is currently no standard treatment for LAL Deficiency other than supportive care. Enzyme replacement therapy (ERT) may be a potential new treatment option for LAL Deficiency patients.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking double blind (subject, caregiver, investigator, outcomes assessor)
Primary purpose treatment
Arm
(Experimental)
Every other week IV infusions of SBC-102
sbc-102 [sebelipase alfa] (1 mg/kg)
(Placebo Comparator)
Every other week infusions of placebo
placebo

Primary Outcomes

Measure
Percentage of Subjects Achieving Alanine Aminotransferase (ALT) Normalization
time frame: Baseline to the end of the double-blind period (week 20)

Secondary Outcomes

Measure
Percentage Change From Baseline in LDL-c
time frame: Baseline to the end of the double-blind period (week 20)
Percentage Change From Baseline in Non-HDL-c
time frame: Baseline to the end of the double-blind period (week 20)
Percentage of Subjects Achieving Aspartate Aminotransferase (AST) Normalization
time frame: Baseline to the end of the double-blind period (week 20)
Percentage Change From Baseline in Triglycerides
time frame: Baseline to the end of the double-blind period (week 20)
Percentage Change From Baseline in HDL-c
time frame: Baseline to the end of the double-blind period (week 20)
Percentage Change From Baseline in Liver Fat Content
time frame: Baseline to the end of the double-blind period (week 20)
Number of Subjects With Improvement in Liver Histology (Decrease of >5% in Hepatic Steatosis Score)
time frame: Baseline to the end of the double-blind period (week 20)
Percentage Change From Baseline in Liver Volume
time frame: Baseline to the end of the double-blind period (week 20)

Eligibility Criteria

Male or female participants at least 4 years old.

Inclusion Criteria: - Subject and/or subject's parent or legal guardian provides informed consent - Subject is ≥4 years of age - Deficiency of LAL enzyme activity confirmed by dried blood spot (DBS) testing at screening - ALT ≥1.5x ULN - Female subjects of childbearing potential must not be pregnant or breastfeeding - Subjects receiving lipid-lowering therapies must be on a stable dose of the medication - Subjects receiving medications for the treatment of non-alcoholic fatty liver disease must be on a stable dose Exclusion Criteria: - Severe hepatic dysfunction (Child-Pugh Class C) - Other medical conditions or comorbidities which, in the opinion of the Investigator, would interfere with study compliance or data interpretation - Previous hematopoietic or liver transplant procedure - Received treatment with high-dose corticosteroids (acute or chronic) within 26 weeks. (Note: Subjects receiving maintenance therapy with low-dose oral, intranasal, topical, or inhaled corticosteroids are considered eligible for the study) - Known hypersensitivity to eggs - Participated in a study employing an investigational medicinal product within 4 weeks prior to randomization

Additional Information

Official title A Multicenter, Randomized, Placebo-Controlled Study of SBC-102 in Patients With Lysosomal Acid Lipase Deficiency
Description Lysosomal Acid Lipase Deficiency (LALD) is a genetic disease which is characterized by abnormal lipid accumulation in many parts of the body due to a marked decrease in activity of the enzyme lysosomal acid lipase (LAL). Although a single disease, LALD presents with two major forms: early onset and late onset. Early onset LALD, also known as Wolman Disease, is characterized by severe malabsorption, growth failure, and hepatic failure and is usually fatal within the first year of life. The late onset form of the disease, also known as Cholesteryl Ester Storage Disease (CESD), occurs in both children and adults and is an under-appreciated cause of fatty liver with prominent microvesicular steatosis and cirrhosis. Although the natural history of the disease has not been well studied, serious liver complications are frequently described including early death and liver transplantation. Other complications includes premature atherosclerosis (hardening of arteries) associated with high levels of total cholesterol and low-density lipoprotein (LDL) cholesterol, often called the "bad" cholesterol. The levels of triglycerides can also be high and the levels of high-density lipoprotein (HDL) cholesterol (the "good" cholesterol) are typically low. Current treatments mainly focus on control of the lipid abnormalities through diet and the use of lipid lowering medications. New treatments are needed for patients with LALD as current treatments only address some aspects of the disease and disease progression to cirrhosis still occurs. In pre-clinical studies and studies in patients with LALD, treatment with SBC-102 (sebelipase alfa) has been shown to produce improvements in markers of liver damage and in the lipid abnormalities. The purpose of this study is to examine the effects of using SBC-102 to treat late onset LALD (CESD) through a placebo-controlled, randomized, double-blinded study in both affected children and adults.
Trial information was received from ClinicalTrials.gov and was last updated in June 2016.
Information provided to ClinicalTrials.gov by Alexion Pharmaceuticals.