Lysosomal Acid Lipase Deficiency MedDRA version: 20.0 Level: HLT Classification code 10024579 Term: Lysosomal storage disorders System Organ Class: 100000004915
Conditions
Interventions
Trade Name: Kanuma
Product Name: sebelipase alfa
Product Code: SBC-102
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: N
USAN: sebelipase alpha
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 2-
Pharmaceutic
Sponsors
Alexion Pharmaceuticals, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Subject and/or subject’s parent or legal guardian understand the full nature and purpose of the study, including possible risks and side effects, and is willing and able to comply with all compulsory study procedures (including liver biopsy and magnetic resonance imaging [MRI] assessments, as applicable) and provides informed consent/permission prior to any study procedures being performed. If the subject is =65 years) no F.1.3.1 Number of subjects for this age range 0
Exclusion criteria
Exclusion criteria: 1. Severe hepatic dysfunction (Child-Pugh Class C). 2. Other medical conditions or comorbidities which, in the opinion of the Investigator, would interfere with study compliance or data interpretation, including but not restricted to severe intercurrent illness, known causes of active liver disease other than LALD (e.g., chronic viral hepatitis, autoimmune hepatitis, alcoholic liver disease, or physician concerns about excess alcohol consumption), human immunodeficiency virus (HIV), poorly-controlled diabetes, or cancers other than non-melanoma skin cancer. 3. Previous hematopoietic or liver transplant procedure. 4. Received treatment with high-dose corticosteroids (acute or chronic) within 26 weeks prior to randomization. (Note: Subjects receiving maintenance therapy with low-dose oral, intranasal, topical, or inhaled corticosteroids are considered eligible for the study.) 5. Participated in a study employing an investigational medicinal product within 30 days prior to randomization. 6. Known hypersensitivity to eggs.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To demonstrate efficacy of Sebelipase alfa, relative to placebo, based on normalisation of ALT in patients with LALD.; Secondary Objective: (1) to demonstrate the efficacy of Sebelipase alfa, relative to placebo, based on the following parameters: decrease in LDL-c, decrease in non-high density lipoprotein cholesterol (HDL-c), normalization of aspartate aminotransferase (AST), decrease in triglycerides, increase in HDL-c, and, in the subset of subjects for whom the assessments are performed, decrease in liver fat content, improvement in hepatic histology, and decrease in liver volume; (2) to evaluate the safety, tolerability, and immunogenicity of Sebelipase alfa therapy; and (3) to further characterise the PK of Sebelipase alfa. ;Primary end point(s): The primary efficacy outcome measure is the proportion of subjects who achieve ALT normalisation (i.e., ALT below the age-and gender-specific ULN provided by the central laboratory performing the assay) at the end of the double-blind treatment period (Week 20).;Timepoint(s) of evaluation of this end point: At the end of the double-blind treatment period (Week 20) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary efficacy outcome measures include the following changes (or normalisation or improvement rates, as applicable) from baseline to the end of the double-blind treatment period: (1) Relative reduction in LDL-c (2) Relative reduction in non-HDL-c (3) The proportion of subjects with an abnormal baseline AST (i.e., > ULN) who achieve AST normalisation, based on age- and gender-specific normal ranges provided by the central laboratory performing this assay (4) Relative reduction in triglycerides (5) Relative increase in HDL-c And, in the subset of subjects for whom the assessments are performed: (6) Relative reduction in liver fat content (7) The proportion of subjects who show improvement in liver histopathology, and (8) Relative reduction in liver volume. ; Timepoint(s) of evaluation of this end point: The following are all assessed at the end of the double-blind treatment period: (1) LDL-c (2) Non-HDL-c (3) AST normalisation (4) Triglycerides (5) HDL-c (6) Right lobe liver fat content (7) Liver histopathology (8) Liver volume | — |
Countries
Argentina, Australia, Belgium, Brazil, Chile, Croatia, Cyprus, Czech Republic, Denmark, France, Germany, Greece, Israel, Italy, Japan, Mexico, Netherlands, Poland, Romania, Russian Federation, South Africa, Spain, Sweden, Taiwan, Turkey, Ukraine, United Kingdom, United States
Contacts
Public ContactRaquel Cerezo
Alexion Pharmaceuticals, Inc.
Outcome results
None listed