Safety and Efficacy Study of Sebelipase Alfa in Patients With Lysosomal Acid Lipase Deficiency

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by Synageva BioPharma Corp.
Sponsor:
Information provided by (Responsible Party):
Synageva BioPharma Corp.
ClinicalTrials.gov Identifier:
NCT02112994
First received: March 20, 2014
Last updated: June 27, 2014
Last verified: June 2014
  Purpose

This study will evaluate the safety and efficacy of sebelipase alfa in a broad population of patients with lysosomal acid lipase deficiency (LALD).


Condition Intervention
Lysosomal Acid Lipase Deficiency
Drug: sebelipase alfa

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Multicenter, Open-Label Study of Sebelipase Alfa in Patients With Lysosomal Acid Lipase Deficiency

Resource links provided by NLM:


Further study details as provided by Synageva BioPharma Corp.:

Primary Outcome Measures:
  • The safety of sebelipase alfa in a more broad population of patients with LALD than have been previously studied. [ Time Frame: 30 days after last study drug infusion (up to 96 weeks) ] [ Designated as safety issue: Yes ]
    • Incidence of adverse events (AEs), SAEs, and infusion-related reactions (IRRs);
    • Changes from Baseline in 12-lead electrocardiograms (ECGs) and clinical laboratory tests;
    • Changes in vital signs during and after infusion, relative to pre-infusion values;
    • Physical examination findings;
    • Use of concomitant medications/therapies;
    • Characterization of anti-drug antibodies (ADAs);
    • Functional and overall development in patients ≤ 6 years of age will be assessed, as determined by Denver II scores.


Secondary Outcome Measures:
  • The effect of sebelipase alfa on lipid metabolism. [ Time Frame: Baseline to end of treatment period (up to 96 weeks) ] [ Designated as safety issue: No ]
    • Decrease in LDL-C;
    • Decrease in non-HDL-C;
    • Decrease in triglycerides;
    • Increase in HDL-C

  • The effect of sebelipase alfa on growth parameters in pediatric patients presenting with evidence of growth delay. [ Time Frame: Baseline to end of treatment period (up to 96 weeks) ] [ Designated as safety issue: No ]
  • The effect of sebelipase alfa on PK parameters. [ Time Frame: Week 0, Week 24, Week 48 ] [ Designated as safety issue: No ]
    PK parameters include: Cmax, time to maximum concentration, area under the serum concentration vs. time curve from time zero to the last measurable time point, area under the serum concentration vs. time curve from time zero to infinity, terminal elimination half-life, serum clearance, and apparent volume of distribution.

  • The effect of sebelipase alfa on liver function (including histopathology). [ Time Frame: Baseline to end of treatment period (up to 96 weeks) ] [ Designated as safety issue: No ]
    • Decrease in Child-Pugh status for patients with Child-Pugh class C or B at Baseline;
    • Decreased United Kingdom Model for End-Stage Liver Disease (UK-ELD) score;
    • Improvement in liver histopathology.


Estimated Enrollment: 20
Study Start Date: May 2014
Estimated Study Completion Date: June 2016
Estimated Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: sebelipase alfa
Intravenous infusion of sebelipase alfa: 1mg/kg every other week
Drug: sebelipase alfa
Intravenous infusion of sebelipase alfa: 1mg/kg every other week
Other Name: SBC-102

Detailed Description:

The primary objective of this study is to evaluate the safety of intravenous infusions of sebelipase alfa in a more broad population of LALD patients than previously studied. Such patients may have been excluded from enrollment in other studies of LALD because of age, disease progression, previous treatment by hematopoietic stem cell or liver transplantation, less common disease manifestations, or disease characteristics that would preclude participation in a placebo-controlled study. This open-label study will include infants >8 months, children and adults. Eligible patients will receive sebelipase alfa at a dose of 1 mg/kg every other week.

  Eligibility

Ages Eligible for Study:   8 Months and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  1. Patient will be > 8 months of age at the time of dosing.
  2. Confirmation of LALD diagnosis as determined by the central lab.
  3. Patients > 8 months but < 4 years of age at Screening will have at least 1 of the following documented clinical manifestations of LALD:

    Dyslipidemia

    • Elevated transaminases (ALT ≥1.5x ULN)
    • Impaired growth
    • Suspected malabsorption
    • Other clinical manifestation of LALD
  4. Patients ≥ 4 years of age at Screening will have at least 1 of the following documented clinical manifestations of LALD:

    • Evidence of advanced liver disease
    • Histologically confirmed disease recurrence in patients with past liver or hematopoietic transplant
    • Persistent dyslipidemia
    • Suspected malabsorption
    • Other clinical manifestation of LALD

Key Exclusion Criteria:

  1. Patient has known causes of active liver disease other than LALD which have not been adequately treated.
  2. Patient received a hematopoietic stem cell or liver transplant <2 years from the time of dosing.
  3. Patient with co-morbidities other than complications due to LALD which are irreversible or associated with a high mortality risk within 6 months, or would interfere with study compliance or data interpretation.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02112994

Contacts
Contact: Emily Radomile 781-357-9983 emily.radomile@synageva.com
Contact: Marina Escudero 781-538-4844 marina.escudero@synageva.com

Locations
United States, Louisiana
Recruiting
Shreveport, Louisiana, United States
United States, Pennsylvania
Recruiting
Sayre, Pennsylvania, United States
Spain
Recruiting
Barcelona, Spain
Recruiting
Madrid, Spain
Sponsors and Collaborators
Synageva BioPharma Corp.
  More Information

No publications provided

Responsible Party: Synageva BioPharma Corp.
ClinicalTrials.gov Identifier: NCT02112994     History of Changes
Other Study ID Numbers: LAL-CL06, 2011-004287-30
Study First Received: March 20, 2014
Last Updated: June 27, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Synageva BioPharma Corp.:
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
Additional relevant MeSH terms:
Cholesterol Ester Storage Disease
Wolman Disease
Metabolic Diseases
Lipidoses
Lipid Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Lysosomal Storage Diseases
Lipid Metabolism Disorders
Infant, Newborn, Diseases

Additional relevant MeSH terms:
Wolman Disease
Cholesterol Ester Storage Disease
Lipidoses
Lipid Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Lysosomal Storage Diseases
Infant, Newborn, Diseases
Lipid Metabolism Disorders
Metabolic Diseases

ClinicalTrials.gov processed this record on September 22, 2014