Clinical Trial: Extension Study to Evaluate the Long-Term Safety, Tolerability, and Efficacy of SBC-102 (Sebelipase Alfa) in Adult Subjects With Lysosomal Acid Lipase Deficiency

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

Official Title: An Open Label Multicenter Extension Study to Evaluate the Long-Term Safety, Tolerability, and Efficacy of SBC-102 in Adult Subjects With Liver Dysfunction Due to Lysosomal Acid Lipase Deficiency Who P

Brief Summary: This is an extension study to the first clinical study of SBC-102 (sebelipase alfa) for the treatment of LAL Deficiency. It is an open label study in adult patients with liver dysfunction due to Lysosomal Acid Lipase (LAL) Deficiency. This study will assess the long-term safety, tolerability, and efficacy of SBC-102. The targeted number for this study is 9 evaluable subjects.

Detailed Summary:

Cholesteryl Ester Storage Disease (CESD) is the late onset phenotype for Lysosomal Acid Lipase (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 patients with other liver conditions.

CESD is an autosomal recessive genetic condition and is characterized by hepatomegaly, persistently abnormal liver function tests (LFTs) and type II hyperlipidemia. Splenomegaly and evidence of mild hypersplenism may affect some patients. Untreated, CESD may lead to fibrosis, cirrhosis, liver failure and death.


Sponsor: Alexion Pharmaceuticals

Current Primary Outcome: ALT and AST Changes From Baseline [ Time Frame: From baseline (study LAL-CL01) to week 12, week 24, week 52, and week 104 ]

Changes from baseline (study LAL-CL01) to specific post-treatment time points in study LAL-CL04 for alanine aminotransferase (ALT) and aspartate aminotransferase (AST).


Original Primary Outcome: Long term safety of SBC-102 including incidence of adverse events [ Time Frame: 3 years ]

The safety and tolerability of 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.


Current Secondary Outcome:

  • Change From Baseline in Liver Volume [ Time Frame: From baseline (study LAL-CL04) to week 10 or 12, week 24, week 52, week 104 ]
    Change in liver volume (in multiples of normal [MN]) from the LAL-CL04 baseline to the indicated post-treatment time point in study LAL-CL04, as assessed by MRI
  • Change From Baseline in Liver Fat Content [ Time Frame: From baseline (study LAL-CL04) to week 10 or 12, week 24, week 52, week 104 ]
    Percentage change in liver fat content from the LAL-CL04 baseline to the indicated post-treatment time point in study LAL-CL04, as assessed by multi-echo gradient-echo MRI
  • GGT and ALP Changes From Baseline [ Time Frame: From baseline (study LAL-CL01) to week 12, week 24, week 52, and week 104 ]
    Changes from baseline (study LAL-CL01) to specific post-treatment time points in study LAL-CL04 for gamma glutamyltransferase (GGT) and alkaline phosphatase (ALP).
  • Lipid Changes From Baseline [ Time Frame: From baseline (study LAL-CL01) to week 10 or 12, week 24, week 52, week 104 ]
    Change from baseline in total cholesterol (Total-C), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), and triglycerides (TG).
  • Serum Ferritin Change From Baseline [ Time Frame: From baseline (study LAL-CL01) to week 12, week 24, week 52, and week 104 ]
  • High Sensitivity C-reactive Protein (Hs-CRP) Change From Baseline [ Time Frame: From baseline (study LAL-CL01) to week 12, week 24, week 52, and week 104 ]


Original Secondary Outcome:

  • Changes in liver and spleen volume and fat content. [ Time Frame: 3 years ]
  • Characterize the pharmacokinetics (e.g. AUC, Cmax, T1/2) of multiple doses of SBC-102 delivered by IV infusion. [ Time Frame: Pre-dose, 10, 15, 20, 40, 60 and 90 minutes during the infusion, the end of the infusion, and at 5, 10, 20, 30, 40, 60 and 120 minutes after completion of the infusion ]
  • Asses pharmacodynamics of SBC-102 on specified biomarkers, including change in transaminases, serum lipids and acute phase reactants. [ Time Frame: 3 years ]


Information By: Alexion Pharmaceuticals

Dates:
Date Received: November 26, 2011
Date Started: November 2011
Date Completion: June 2017
Last Updated: January 23, 2017
Last Verified: January 2017