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

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: A Multicenter, Open-Label Study of Sebelipase Alfa in Patients With Lysosomal Acid Lipase Deficiency

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

Detailed Summary: 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.
Sponsor: Alexion Pharmaceuticals

Current Primary Outcome: 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 144 weeks) ]

  • 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.


Original Primary Outcome: 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) ]

  • 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.


Current Secondary Outcome:

  • The effect of sebelipase alfa on lipid metabolism. [ Time Frame: Baseline to end of treatment period (up to 144 weeks) ]
    • 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 144 weeks) ]
  • The effect of sebelipase alfa on PK parameters. [ Time Frame: Week 0, Week 24, Week 48 ]
    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 144 weeks) ]
    • 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.


Original Secondary Outcome:

  • The effect of sebelipase alfa on lipid metabolism. [ Time Frame: Baseline to end of treatment period (up to 96 weeks) ]
    • 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) ]
  • The effect of sebelipase alfa on PK parameters. [ Time Frame: Week 0, Week 24, Week 48 ]
    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) ]
    • 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.


Information By: Alexion Pharmaceuticals

Dates:
Date Received: March 20, 2014
Date Started: May 2014
Date Completion: December 2017
Last Updated: May 17, 2017
Last Verified: May 2017