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

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ClinicalTrials.gov Identifier: NCT01307098
Recruitment Status : Completed
First Posted : March 2, 2011
Results First Posted : December 11, 2018
Last Update Posted : December 11, 2018
Sponsor:
Information provided by (Responsible Party):
Alexion Pharmaceuticals

Tracking Information
First Submitted Date  ICMJE March 1, 2011
First Posted Date  ICMJE March 2, 2011
Results First Submitted Date  ICMJE October 30, 2018
Results First Posted Date  ICMJE December 11, 2018
Last Update Posted Date December 11, 2018
Actual Study Start Date  ICMJE April 25, 2011
Actual Primary Completion Date January 6, 2012   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 10, 2018)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: March 1, 2011)
Safety and Tolerability of SBC-102 [ Time Frame: 4 weeks ]
The safety and tolerability of weekly infusions of SBC-102 will be assessed by routine monitoring of patients for adverse events (AEs) and monitoring changes from baseline in physical examination findings, vital signs, clinical laboratory evaluations, immunogenicity tests and concomitant therapies.
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE
 (submitted: March 1, 2011)
Pharmacokinetics of SBC-102 [ Time Frame: 4 weeks ]
Characterize the pharmacokinetics of SBC-102 delivered by IV infusion after single and multiple doses.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety, Tolerability and Pharmacokinetics of SBC-102 (Sebelipase Alfa) in Adult Participants With Lysosomal Acid Lipase Deficiency
Official Title  ICMJE 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
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Cholesterol Ester Storage Disease(CESD)
  • Lysosomal Acid Lipase Deficiency
  • LAL-Deficiency
Intervention  ICMJE
  • Drug: Sebelipase alfa 0.35 mg/kg
    Sebelipase alfa is a recombinant human lysosomal acid lipase.
    Other Names:
    • Kanuma
    • SBC-102
  • Drug: Sebelipase alfa 1 mg/kg
    Sebelipase alfa is a recombinant human lysosomal acid lipase.
    Other Names:
    • Kanuma
    • SBC-102
  • Drug: Sebelipase alfa 3 mg/kg
    Sebelipase alfa is a recombinant human lysosomal acid lipase.
    Other Names:
    • Kanuma
    • SBC-102
Study Arms  ICMJE
  • Experimental: Sebelipase alfa 0.35 mg/kg
    Cohort 1: Participants were administered once weekly (qw) infusions of 0.35 mg/kg sebelipase alfa.
    Intervention: Drug: Sebelipase alfa 0.35 mg/kg
  • Experimental: Sebelipase alfa 1 mg/kg
    Cohort 2: Participants were administered qw infusions of 1 mg/kg sebelipase alfa.
    Intervention: Drug: Sebelipase alfa 1 mg/kg
  • Experimental: Sebelipase alfa 3 mg/kg
    Cohort 3: Participants were administered qw infusions of 3 mg/kg sebelipase alfa.
    Intervention: Drug: Sebelipase alfa 3 mg/kg
Publications * Balwani M, Breen C, Enns GM, Deegan PB, Honzík 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 1, 2011)
9
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE January 6, 2012
Actual Primary Completion Date January 6, 2012   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Czechia,   France,   United Kingdom,   United States
Removed Location Countries Czech Republic
 
Administrative Information
NCT Number  ICMJE NCT01307098
Other Study ID Numbers  ICMJE LAL-CL01
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Alexion Pharmaceuticals
Study Sponsor  ICMJE Alexion Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Alexion Pharmaceuticals
Verification Date December 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP