A study of SBC-102 (enzyme replacement therapy) in patients with lysosomal acid lipase deficiency

• Register: EUCTR
• Last refreshed on: 30 June 2019
• Main ID: EUCTR2011-002750-31-DE
• Date of registration: 29/01/2013
• Prospective Registration: Yes
• Primary sponsor: Alexion Pharmaceuticals, Inc.
• Public title: A study of SBC-102 (enzyme replacement therapy) in patients with lysosomal acid lipase deficiency
• Scientific title: A multicenter, randomized, placebo-controlled study of SBC-102 in patients with lysosomal acid lipase deficiency - ARISE (Acid Lipase Replacement Investigating Safety and Efficacy)
• Date of first enrolment: 29/05/2013
• Target sample size: 55
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2011-002750-31
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: yes; Other trial design description: 20-wks double-blind treatment + an open-label extension of up to 130 wks + 104 wks of extension; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

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

• Name: Raquel Cerezo
• Affiliation: Alexion Pharmaceuticals, Inc.

• Name: Raquel Cerezo
• Affiliation: Alexion Pharmaceuticals, Inc.

Key inclusion & exclusion 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 <18 years of age, he/she is willing to provide assent where required per local regulations and if deemed able to do so.
2. Subject is =4 years of age on the date of informed consent.
3. Deficiency of lysosomal acid lipase (LAL) enzyme activity confirmed by dried blood spot (DBS) testing at screening, based on the definition of deficiency provided by the central laboratory performing the assay.
4. ALT =1.5x ULN (based on the age- and gender-specific normal ranges of the central laboratory performing the assay) on 2 consecutive screening ALT measurements obtained at least 1 week apart.
5. Female subjects of childbearing potential must (a) have negative serum pregnancy test at screening (b) cannot be breastfeeding, and (c) must agree to use a medically acceptable method of preventing conception from the screening visit until 4 weeks after the last dose of study drug administered under this protocol. A female of childbearing potential is defined as a menarchal female who has not had a hysterectomy, bilateral oophorectomy, or medically documented ovarian failure, and who is not postmenopausal.
6. Subjects receiving lipid-lowering therapies must be on a stable dose of the medication for at least 6 weeks prior to randomization and be willing to remain on a stable dose for at least the first 32 weeks of treatment in the study.
7. Subjects receiving medications for the treatment of non-alcoholic fatty liver disease (e.g., glitazones, high-dose vitamin E, metformin, ursodeoxycholic acid [UDCA]) must be on a stable dose for at least 16 weeks prior to randomization and be willing to remain on a stable dose for at least the first 32 weeks of treatment in the study.
Are the trial subjects under 18? yes
Number of subjects for this age range: 26
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 29
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 0

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.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Lysosomal Acid Lipase Deficiency
MedDRA version: 20.0 Level: HLT Classification code 10024579 Term: Lysosomal storage disorders System Organ Class: 100000004915

Therapeutic area: Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

Intervention(s)

Trade Name: Kanuma
Product Name: sebelipase alfa
Product Code: SBC-102
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: NA
CAS Number: 1276027-63-4
Current Sponsor code: SBC-102
Other descriptive name: lysosomal acid lipase, Esterase, cholesterol (human gene LIPA), Lysosomal acid lipase (human gene LIPA); USAN: sebelipase alpha
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 2-
Pharmaceutical form of the placebo: Solution for infusion
Route of administration of the placebo: Intravenous use

Primary Outcome(s)

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 Outcome(s)

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

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.

Secondary ID(s)

LAL-CL02

Source(s) of Monetary Support

Alexion Pharmaceuticals, Inc.

Ethics review

Status: Approved
Approval date:
Contact:

Results

• Results available: Yes
• Date Posted: 06/08/2015
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2011-002750-31/results