search
Back to results

Safety, Tolerability and Pharmacokinetics of SBC-102 (Sebelipase Alfa) in Adult Participants With Lysosomal Acid Lipase Deficiency

Primary Purpose

Cholesterol Ester Storage Disease(CESD), Lysosomal Acid Lipase Deficiency, LAL-Deficiency

Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Sebelipase alfa 0.35 mg/kg
Sebelipase alfa 1 mg/kg
Sebelipase alfa 3 mg/kg
Sponsored by
Alexion
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cholesterol Ester Storage Disease(CESD) focused on measuring 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

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Male or female participants ≥ 18 and ≤ 65 years of age
  • Documented decreased LAL activity
  • Evidence of liver involvement

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
  • Aspartate aminotransferase and/or alanine aminotransferase persistently elevated > 3x upper limit of normal at screening
  • Previous hemopoietic bone marrow or liver transplant
  • Current history of alcohol abuse

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Sebelipase alfa 0.35 mg/kg

Sebelipase alfa 1 mg/kg

Sebelipase alfa 3 mg/kg

Arm Description

Cohort 1: Participants were administered once weekly (qw) infusions of 0.35 mg/kg sebelipase alfa.

Cohort 2: Participants were administered qw infusions of 1 mg/kg sebelipase alfa.

Cohort 3: Participants were administered qw infusions of 3 mg/kg sebelipase alfa.

Outcomes

Primary Outcome Measures

Number Of Participants Reporting TEAEs And Infusion-Related Reactions (IRRs)
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-related reactions (IRRs). The number of participants who discontinued from the study due to a TEAE is also presented. An IRR was defined as any adverse event that occurred between the start of the infusion and 4 hours after completion 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.

Secondary Outcome Measures

Full Information

First Posted
March 1, 2011
Last Updated
December 10, 2018
Sponsor
Alexion
search

1. Study Identification

Unique Protocol Identification Number
NCT01307098
Brief Title
Safety, Tolerability and Pharmacokinetics of SBC-102 (Sebelipase Alfa) in Adult Participants With Lysosomal Acid Lipase Deficiency
Official Title
An Open-Label Multicenter Study to Evaluate the Safety, Tolerability and Pharmacokinetics of SBC-102 in Adult Participants With Liver Dysfunction Due to Lysosomal Acid Lipase Deficiency
Study Type
Interventional

2. Study Status

Record Verification Date
December 2018
Overall Recruitment Status
Completed
Study Start Date
April 25, 2011 (Actual)
Primary Completion Date
January 6, 2012 (Actual)
Study Completion Date
January 6, 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Alexion

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This was the first clinical study of SBC-102 (sebelipase alfa) for the treatment of Lysosomal Acid Lipase (LAL) Deficiency. It was an open-label dose escalation study in adult participants with liver dysfunction due to LAL Deficiency and was designed to examine 3 doses of sebelipase alfa. The targeted number for this study was 9 evaluable participants.
Detailed Description
The study was composed of a screening period, a treatment period, and a post-treatment follow-up period (including an End of Study visit). Participants who successfully completed screening assessments to determine study eligibility were allocated to 3 sequential cohorts (0.35, 1, or 3 milligrams/kilogram [mg/kg]). Within each cohort, one participant was initially dosed and, if sebelipase alfa was deemed safe and well tolerated in this participant (based on at least 24 hours of monitoring), dosing was allowed to be initiated for the remaining participants in the cohort. Initiation of dosing in the next cohort occurred only after all participants in the preceding cohort had been monitored for at least 5 days after the second infusion, without any evidence of significant safety signals, and an independent Safety Committee had reviewed the cumulative safety data and provided their recommendation on the acceptability of beginning dosing in the next cohort. Cholesteryl Ester Storage Disease (CESD) is the late onset phenotype for 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 participants with other liver conditions. CESD is an autosomal recessive genetic condition and is characterized by hepatomegaly, persistently abnormal liver function tests and type II hyperlipidemia. Splenomegaly and evidence of mild hypersplenism may affect some participants. Untreated, CESD may lead to fibrosis, cirrhosis, liver failure and death.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cholesterol Ester Storage Disease(CESD), Lysosomal Acid Lipase Deficiency, LAL-Deficiency
Keywords
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
9 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Sebelipase alfa 0.35 mg/kg
Arm Type
Experimental
Arm Description
Cohort 1: Participants were administered once weekly (qw) infusions of 0.35 mg/kg sebelipase alfa.
Arm Title
Sebelipase alfa 1 mg/kg
Arm Type
Experimental
Arm Description
Cohort 2: Participants were administered qw infusions of 1 mg/kg sebelipase alfa.
Arm Title
Sebelipase alfa 3 mg/kg
Arm Type
Experimental
Arm Description
Cohort 3: Participants were administered qw infusions of 3 mg/kg sebelipase alfa.
Intervention Type
Drug
Intervention Name(s)
Sebelipase alfa 0.35 mg/kg
Other Intervention Name(s)
Kanuma, SBC-102
Intervention Description
Sebelipase alfa is a recombinant human lysosomal acid lipase.
Intervention Type
Drug
Intervention Name(s)
Sebelipase alfa 1 mg/kg
Other Intervention Name(s)
Kanuma, SBC-102
Intervention Description
Sebelipase alfa is a recombinant human lysosomal acid lipase.
Intervention Type
Drug
Intervention Name(s)
Sebelipase alfa 3 mg/kg
Other Intervention Name(s)
Kanuma, SBC-102
Intervention Description
Sebelipase alfa is a recombinant human lysosomal acid lipase.
Primary Outcome Measure Information:
Title
Number Of Participants Reporting TEAEs And Infusion-Related Reactions (IRRs)
Description
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-related reactions (IRRs). The number of participants who discontinued from the study due to a TEAE is also presented. An IRR was defined as any adverse event that occurred between the start of the infusion and 4 hours after completion 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.
Time Frame
Screening up to Day 52

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Male or female participants ≥ 18 and ≤ 65 years of age Documented decreased LAL activity Evidence of liver involvement 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 Aspartate aminotransferase and/or alanine aminotransferase persistently elevated > 3x upper limit of normal at screening Previous hemopoietic bone marrow or liver transplant Current history of alcohol abuse
Facility Information:
City
Stanford
State/Province
California
ZIP/Postal Code
94305
Country
United States
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213
Country
United States
City
Prague
ZIP/Postal Code
12000
Country
Czechia
City
Paris
ZIP/Postal Code
75743
Country
France
City
Cambridge
ZIP/Postal Code
CB20QQ
Country
United Kingdom
City
Manchester
ZIP/Postal Code
M139WL
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
Undecided
Citations:
PubMed Identifier
23348766
Citation
Balwani M, Breen C, Enns GM, Deegan PB, Honzik T, Jones S, Kane JP, Malinova V, Sharma R, Stock EO, Valayannopoulos V, Wraith JE, Burg J, Eckert S, Schneider E, Quinn AG. Clinical effect and safety profile of recombinant human lysosomal acid lipase in patients with cholesteryl ester storage disease. Hepatology. 2013 Sep;58(3):950-7. doi: 10.1002/hep.26289. Epub 2013 Mar 28.
Results Reference
result
Links:
URL
http://alexion.com
Description
Website

Learn more about this trial

Safety, Tolerability and Pharmacokinetics of SBC-102 (Sebelipase Alfa) in Adult Participants With Lysosomal Acid Lipase Deficiency

We'll reach out to this number within 24 hrs