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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Alexion Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT01488097
First received: November 26, 2011
Last updated: April 5, 2016
Last verified: April 2016

November 26, 2011
April 5, 2016
November 2011
March 2014   (final data collection date for primary outcome measure)
ALT and AST Changes From Baseline [ Time Frame: From baseline (study LAL-CL01) to week 12, week 24, week 52, and week 104 ] [ Designated as safety issue: No ]
Changes from baseline (study LAL-CL01) to specific post-treatment time points in study LAL-CL04 for alanine aminotransferase (ALT) and aspartate aminotransferase (AST).
Long term safety of SBC-102 including incidence of adverse events [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
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.
Complete list of historical versions of study NCT01488097 on ClinicalTrials.gov Archive Site
  • Change From Baseline in Liver Volume [ Time Frame: From baseline (study LAL-CL04) to week 10 or 12, week 24, week 52, week 104 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Changes in liver and spleen volume and fat content. [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Asses pharmacodynamics of SBC-102 on specified biomarkers, including change in transaminases, serum lipids and acute phase reactants. [ Time Frame: 3 years ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Extension Study to Evaluate the Long-Term Safety, Tolerability, and Efficacy of SBC-102 (Sebelipase Alfa) in Adult Subjects With Lysosomal Acid Lipase Deficiency
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 Previously Received Treatment in Study LAL-CL01
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.

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.

Interventional
Phase 2
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Cholesterol Ester Storage Disease(CESD)
  • Lysosomal Acid Lipase Deficiency
  • Drug: SBC-102 (sebelipase alfa)
    Weekly IV infusions Dose A of SBC-102 (sebelipase alfa) and bi-weekly infusions of Dose B or Dose C of SBC-102 (sebelipase alfa)
  • Drug: SBC-102 (sebelipase alfa)
    Weekly IV infusions Dose B of SBC-102 (sebelipase alfa) and bi-weekly infusions of Dose B or Dose C of SBC-102 (sebelipase alfa)
  • Drug: SBC-102 (sebelipase alfa)
    Weekly IV infusions Dose C of SBC-102 (sebelipase alfa) and bi-weekly infusions of Dose C of SBC-102 (sebelipase alfa)
  • Experimental: Cohort 1
    Weekly IV infusions of Dose A of SBC-102 (sebelipase alfa) and bi-weekly IV infusions of Dose B or Dose C of SBC-102 (sebelipase alfa)
    Intervention: Drug: SBC-102 (sebelipase alfa)
  • Experimental: Cohort 2
    Weekly IV infusions of Dose B of SBC-102 (sebelipase alfa) and bi-weekly infusions of Dose B or Dose C of SBC-102 (sebelipase alfa)
    Intervention: Drug: SBC-102 (sebelipase alfa)
  • Experimental: Cohort 3
    Weekly IV infusions of Dose C of SBC-102 (sebelipase alfa) and bi-weekly infusions of Dose C of SBC-102 (sebelipase alfa)
    Intervention: Drug: SBC-102 (sebelipase alfa)
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.
 
Active, not recruiting
8
June 2017
March 2014   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Subject received all 4 scheduled doses of SBC-102 in study LAL-CL01 with no life-threatening or unmanageable study drug toxicity.

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
Both
18 Years to 65 Years   (Adult)
No
Contact information is only displayed when the study is recruiting subjects
United States,   Canada,   Czech Republic,   France,   United Kingdom
 
NCT01488097
LAL-CL04
Yes
Not Provided
Not Provided
Alexion Pharmaceuticals
Alexion Pharmaceuticals
Not Provided
Not Provided
Alexion Pharmaceuticals
April 2016

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