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

December 10, 2018 updated by: Alexion Pharmaceuticals

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

9

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Czechia
      • Prague, Czechia, 12000
  • France
      • Paris, France, 75743
  • United Kingdom
      • Cambridge, United Kingdom, CB20QQ
      • Manchester, United Kingdom, M139WL
  • United States
    • California
      • Stanford, California, United States, 94305
    • New York
      • New York, New York, United States, 10029
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15213

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NON_RANDOMIZED
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Sebelipase alfa 0.35 mg/kg
Cohort 1: Participants were administered once weekly (qw) infusions of 0.35 mg/kg sebelipase alfa.
Drug: Sebelipase alfa 0.35 mg/kg
Sebelipase alfa is a recombinant human lysosomal acid lipase.
Other Names:
  • SBC-102
  • Kanuma
EXPERIMENTAL: Sebelipase alfa 1 mg/kg
Cohort 2: Participants were administered qw infusions of 1 mg/kg sebelipase alfa.
Drug: Sebelipase alfa 1 mg/kg
Sebelipase alfa is a recombinant human lysosomal acid lipase.
Other Names:
  • SBC-102
  • Kanuma
EXPERIMENTAL: Sebelipase alfa 3 mg/kg
Cohort 3: Participants were administered qw infusions of 3 mg/kg sebelipase alfa.
Drug: Sebelipase alfa 3 mg/kg
Sebelipase alfa is a recombinant human lysosomal acid lipase.
Other Names:
  • SBC-102
  • Kanuma

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number Of Participants Reporting TEAEs And Infusion-Related Reactions (IRRs)
Time Frame: Screening up to Day 52
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.
Screening up to Day 52

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Alexion Pharmaceuticals

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

April 25, 2011

Primary Completion (ACTUAL)

January 6, 2012

Study Completion (ACTUAL)

January 6, 2012

Study Registration Dates

First Submitted

March 1, 2011

First Submitted That Met QC Criteria

March 1, 2011

First Posted (ESTIMATE)

March 2, 2011

Study Record Updates

Last Update Posted (ACTUAL)

December 11, 2018

Last Update Submitted That Met QC Criteria

December 10, 2018

Last Verified

December 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • LAL-CL01

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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