Status:

COMPLETED

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

Lead Sponsor:

Amsterdam Molecular Therapeutics

Collaborating Sponsors:

The Clinical Trial Company

Conditions:

Familial Lipoprotein Lipase Deficiency

Eligibility:

All Genders

18+ years

Phase:

PHASE2

PHASE3

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 p...

Detailed Description

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 acu...

Eligibility Criteria

Inclusion

  • Being diagnosed with LPLD defined as:
  • Confirmed homozygosity or compound heterozygosity for the mutations in the LPL gene, resulting in LPL deficiency
  • Having a post heparin plasma LPL activity of ≤ 20% of normal or a well defined mutation for which it is documented that the LPL mass and activity are within the limits described above
  • Having a history of pancreatitis
  • Having fluctuating TG concentrations with median fasting plasma TG concentrations \> 10.00 mmol/L
  • Being in good general physical health with, in the opinion of the investigator:
  • No other clinically significant and relevant abnormalities in the medical history which could interfere with the participation to the study
  • No clinically significant abnormalities at the physical examination which could interfere with the participation to the study
  • No clinically significant abnormalities at the routine laboratory evaluation performed prior to the trial
  • Women of non-child bearing potential or with a negative pregnancy test.
  • Non breast feeding women
  • Women using appropriate contraceptive (if relevant) and their partner using barrier contraception 2 weeks before starting immunosuppressive therapy
  • Men practicing barrier birth control and their partner using appropriate contraception.
  • Willing to fully comply with all study procedures and requirements of the trial such as restrictions to a low-fat diet.

Exclusion

  • Having a chronic inflammatory muscle disease.
  • Any current or relevant previous history of serious, severe or unstable physical or psychiatric illness, any medical disorder that may make the subject unlikely to fully complete the study, or any condition that presents undue risk from the study medication or procedures based on the investigator's opinion(eg. malignant neoplasia)
  • Active infectious disease of any nature, including clinically active viral infections
  • Having one of the following outcomes from the blood screening tests after appropriate correction due to the presence of chylomicronemia:
  • Platelet count \< 100 x 109 /L
  • Hemoglobin \< 6.2 mmol/L
  • Liver function disturbances (bilirubin ≥1.5 x normal, ALT \> 2 x ULN (upper limit of normal)
  • CPK \> 2 x ULN
  • Cockcroft-Gault estimated creatinine clearance \< 50cc/min
  • PT and PTT outside normal range or not determinable unless judged as acceptable for the subjects by the investigator
  • Having a positive test for HIV, Hepatitis B, Hepatitis C or being positive for tuberculosis
  • Obesity defined as body mass index (BMI) \> 30 kg/m2
  • Having a recent history of alcohol or drug abuse e.g. barbiturates, cannabinoids and amphetamines, and the subject is positive in a urine screen for drugs of abuse
  • Using anti-coagulants
  • Participation in another clinical trial or receipt of any other investigational drug within 30 days of screening or planning to participate in another clinical trial during the course of the study, except observational studies
  • Subjects which cannot be treated with immunosuppressive medication or steroids
  • Known to be allergic to any constituent of the therapy (including the immune suppressors) or a having a condition that prohibits the use of therapy
  • Received previous treatment with AMT-010, Alipogene tiparvovec or other gene therapy investigational product
  • Requiring a post heparin plasma LPL activity test for diagnostic confirmation and having a history of heparin induced thrombocytopenia or other heparin related complications

Key Trial Info

Start Date :

February 1 2009

Trial Type :

INTERVENTIONAL

Allocation :

ACTUAL

End Date :

April 1 2011

Estimated Enrollment :

5 Patients enrolled

Trial Details

Trial ID

NCT00891306

Start Date

February 1 2009

End Date

April 1 2011

Last Update

September 29 2011

Active Locations (2)

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Page 1 of 1 (2 locations)

1

ECOGENE-21 Clinical Trial Center / Centre de santé et de services sociaux de Chicoutimi

Chicoutimi, Quebec, Canada, G7H 5H6

2

Centre des Maladies Lipidiques de Québec

Québec, Quebec, Canada, G1V 4M6