NCT01109498

Safety and Efficacy in LPL-Deficient Subjects of AMT-011, an Adeno-Associated Viral Vector Expressing Human Lipoprotein Lipase [S447X]

A Study to Determine the Safety and Efficacy in Lipoprotein Lipase-Deficient Subjects After Intramuscular Administration of AMT-011, an Adeno-Associated Viral Vector Expressing Human Lipoprotein LipaseS447X

• Status: Unknown
• Phase: Phase 2 / Phase 3
• Study type: Interventional
• Enrollment: 14 (actual)
• Sponsor: Amsterdam Molecular Therapeutics · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Detailed description

The CT-AMT-011-01 study is an open-label, dose-escalating study evaluating the safety and efficacy of a single intramuscular administration of AMT-011 (at multiple sites). The study will be performed in the Community Genomic medicineCenter (CGMC) Chicoutimi, Canada, under the supervision of their medical ethical committee and according to the local biosafety procedures. The study participants will be treated under the responsibility of a Principal Investigator specialised in the treatment of lipid disorders. A total number of 14 subjects will be administered. Participants will be screened 3 weeks prior to administration of AMT-011 and will be evaluated for 12 weeks post administration in this study. After the study, subjects will be followed up long term with particular emphasis on the safety and efficacy aspects of LPL gene therapy using AMT-011. Subjects will be evaluated at the clinical site at 19 weeks, 26 weeks, 39 weeks, 1 year, 1.5 years, 2 years, 3 years, 4 years and 5 years after administration of AMT-011. The TG values that are obtained at week 26 will be used for secondary efficacy analysis.

Conditions

• Familial Lipoprotein Lipase Deficiency

Interventions

Type	Name	Description
GENETIC	Alipogene Tiparvovec (AMT-011), Human LPL [S447X]	intra muscular, 1 x E12 gc per kg body weight, injected in a single series of intramuscular injections
DRUG	Mycophenolate mofetil	oral, 2 g/day, day -3 till week 12
GENETIC	Alipogene Tiparvovec (AMT-011), Human LPL [S447X]	intra muscular, 3 x E11 gc per kg body weight, injected in a single series of intramuscular injections
DRUG	cyclosporine	oral, 3 mg/kg/day, day -3 till week 12

Timeline

• Start date: 2007-08-01
• Primary completion: 2013-06-01
• Completion: 2013-06-01
• First posted: 2010-04-23
• Last updated: 2011-09-30

Locations

1 site across 1 country: Canada