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Clinical Trial in Infants With Rapidly Progressive Lysosomal Acid Lipase Deficiency

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02193867
Recruitment Status : Active, not recruiting
First Posted : July 18, 2014
Last Update Posted : September 6, 2017
Information provided by (Responsible Party):
Alexion Pharmaceuticals

Tracking Information
First Submitted Date  ICMJE July 7, 2014
First Posted Date  ICMJE July 18, 2014
Last Update Posted Date September 6, 2017
Actual Study Start Date  ICMJE June 2014
Estimated Primary Completion Date April 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 16, 2014)
Long-term safety [ Time Frame: Up to 3 years ]
  • Incidence of AEs and SAEs
  • Changes from baseline clinical laboratory tests
  • Changes in vitals
  • Physical examination findings
  • Use of concomitant medications
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02193867 on Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: July 16, 2014)
  • Survival at 12 months of age [ Time Frame: 12 months ]
  • Survival beyond 12 months of age [ Time Frame: Up to 3 years ]
  • Growth [ Time Frame: Up to 3 years ]
    • changes from baseline in percentiles and/or z-scores for weight for age (WFA), weight for length (WFL)/weight for height(WFH), and length for age (LFA)/height for age (HFA)
    • growth status indicators of underweight, wasting, and stunting
    • changes from baseline in z scores for head circumference-for-age (HCFA) and mid-upper arm circumference-for-age (MUACFA)
  • Hematological parameters [ Time Frame: Up to 3 years ]
    • Changes from baseline in aspartate aminotransferase (AST) and ALT
    • Normalization of hemoglobin levels without requirement for blood transfusion
    • Change from baseline in serum ferritin.
  • Characterize the PK of sebelipase alfa [ Time Frame: Up to 3 years ]
    Cmax of sebelipase alfa
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE Clinical Trial in Infants With Rapidly Progressive Lysosomal Acid Lipase Deficiency
Official Title  ICMJE A Phase 2, Open Label, Multicenter Study to Evaluate the Safety, Tolerability, Efficacy, and Pharmacokinetics of Sebelipase Alfa in Infants With Rapidly Progressive Lysosomal Acid Lipase Deficiency
Brief Summary This is an open-label, repeat-dose, study of sebelipase alfa in infants with rapidly progressive LAL Deficiency. Eligible subjects will receive once-weekly infusions of sebelipase alfa for up to 3 years.
Detailed Description

Lysosomal Acid Lipase (LAL) Deficiency is a rare autosomal recessive lipid storage disorder that is caused by a marked decrease or almost complete absence of the LAL enzyme, leading to the accumulation of these lipids, predominately cholesteryl esters and triglycerides, in various tissues and cell types. In the liver, accumulation of lipids leads to hepatomegaly, liver dysfunction, and hepatic failure. In the small intestine, lipid-laden macrophage accumulation in the lamina propria leads to profound malabsorption.

LAL Deficiency presenting in infancy is extremely rare form of LAL Deficiency. It is characterized by profound malabsorption, growth failure, and hepatic failure, and is usually fatal in the first 6 months of life. There is currently no safe or effective therapy for the treatment of LAL Deficiency.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Lysosomal Acid Lipase Deficiency
Intervention  ICMJE Drug: sebelipase alfa
Sebelipase alfa is a recombinant human lysosomal acid lipase (rhLAL). The investigational medicinal product is an enzyme replacement therapy intended for treatment of patients with Lysosomal Acid Lipase Deficiency. Dosing will occur once weekly for up to three years.
Study Arms  ICMJE Experimental: Cohort 1
Weekly IV infusions of sebelipase alfa
Intervention: Drug: sebelipase alfa
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 Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: July 16, 2014)
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE April 2018
Estimated Primary Completion Date April 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Subject's parent or legal guardian (if applicable) consents to participation in the study.
  2. Confirmation of LAL Deficiency diagnosis as determined by a Sponsor approved central laboratory.
  3. Substantial clinical concerns, in the opinion of Investigator and Sponsor, of rapid disease progression requiring urgent medical intervention including, but not restricted to, the following:

    • Marked abdominal distension and hepatomegaly
    • Failure to thrive
    • Disturbance of coagulation
    • Severe anemia
    • Sibling with rapidly progressive course of LAL Deficiency

Exclusion Criteria:

  1. Clinically important concurrent disease
  2. Subject will be > 8 months of age at the time of first dosing.
  3. Subject has received an investigational medicinal product other than sebelipase alfa within 14 days prior to the first dose of sebelipase alfa in this study.
  4. Myeloablative preparation, or other systemic pre-transplant conditioning, for hematopoietic stem cell or liver transplantation.
  5. Previous hematopoietic stem cell or liver transplant.
  6. Known hypersensitivity to eggs.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE up to 8 Months   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Italy,   United Kingdom,   United States
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT02193867
Other Study ID Numbers  ICMJE LAL-CL08
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Alexion Pharmaceuticals
Study Sponsor  ICMJE Alexion Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Mark Friedman, MD Alexion Pharmaceuticals
PRS Account Alexion Pharmaceuticals
Verification Date September 2017

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