Clinical Trial: Efficacy and Safety of Human Lipoprotein Lipase (LPL)[S447X] Expressed by an Adeno-Associated Viral Vector in LPL-deficient Subjects

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: An Open-label Study to Assess the Efficacy and Safety of Alipogene Tiparvovec (AMT-011), Human LPL [S447X], Expressed by an Adeno-Associated Viral Vector After Intramuscular Administration in LPL-defi

Brief Summary: This trial is designed to expand the currently available data on the safety and efficacy of alipogene tiparvovec treatment in lipoprotein lipase deficiency (LPLD) and to further the understanding of possible mechanisms of action of the therapy.

Detailed Summary:

LPLD is a rare autosomal recessive disorder, characterized by the presence of marked chylomicronemia and hence hypertriglyceridemia. Clinically the most severe manifestation of chylomicronemia, is acute pancreatitis, which can be lethal. There is no effective therapy available to modulate the course of the illness and prevent complications for these patients. The current clinical management consists of severe reduction of dietary fat that is hard if not almost impossible to comply with. LPLD subjects continue to experience pancreatitis attacks, and are admitted to intensive care units on several occasions.

Alipogene tiparvovec corrects or restores lipoprotein lipase (LPL) function long term, and hence reverses some symptoms, halts the disease progression and prevents further complications. Alipogene tiparvovec gene therapy ensures that a catabolically beneficial variant of the human LPL gene, LPL[S447X] is expressed and active in the relevant tissues in humans. Delivery of the gene is realized via intramuscular injection of an adeno-associated viral vector, pseudotyped with AAV1 capsids.


Sponsor: Amsterdam Molecular Therapeutics

Current Primary Outcome: Reduction of triglyceride (TG) concentrations [ Time Frame: 12 weeks ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Reduction of chylomicrons and/or chylomicron-TG ratio [ Time Frame: 12 weeks ]
  • To determine the biological activity and expression of the lipoprotein lipase [LPLS447X] transgene product [ Time Frame: 14 weeks ]
  • To assess the safety profile [ Time Frame: 14 weeks ]
  • To assess shedding of viral vector [ Time Frame: 14 weeks ]


Original Secondary Outcome: Same as current

Information By: Amsterdam Molecular Therapeutics

Dates:
Date Received: April 30, 2009
Date Started: February 2009
Date Completion:
Last Updated: September 28, 2011
Last Verified: September 2011