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

This is an interventional treatment trial for Familial Lipoprotein Lipase Deficiency focused on measuring LPLD, Lipoprotein Lipase Deficiency, Chylomicronaemia, Genetherapy, AAV, Alipogene Tiparvovec, AMT-011, Lipoprotein Lipase Read More

Inclusion Criteria:

• Eligible Population Study participants must have participated in the preceding observation study (Prep-02: Appendix III) and be diagnosed with lipoprotein lipase deficiency, meeting the following criteria: (I) Their lipoprotein lipase activity levels in post-heparin plasma should be ≤20 % of normal; (II) Confirmed homozygocity or compound heterozygocity for mutations in the LPL gene; (III) Post-heparin plasma LPL mass should be >5% of normal; (IV) Median fasting plasma TG concentrations >10.00mmol/L, as determined on the basis of 5 consecutive time points in the preceding observation study with a history of pancreatitis.
• General Health The participant must be in good general physical health with, in the opinion of the investigator, no other clinically significant and relevant abnormalities of medical history, and no abnormalities at the physical examination and routine laboratory evaluation performed prior to the trial.
• Age Age ≥18 years old.
• Sex Male or female. Females must be of non-child bearing potential or with a negative pregnancy test and not breast feeding. Female subjects must use appropriate contraception (if relevant) and their spouse must use barrier contraception for the duration of the study (12 weeks). Males must practice barrier birth control and their spouse should use appropriate contraception until three consecutive semen samples, taken at least 75 days after administration, are negative for AMT-011 vector DNA.
• Compliance The participant is willing to fully comply with all study procedures and requirements of the trial such as restrictions to a low-fat diet (see section 8.1).
• Consent The participant has the mental ability to give voluntary written informed consent to participate in the study.

Exclusion Criteria:

• Disease
• Apolipoprotein CII deficiency.
• Inflammatory muscle disease (e.g. myositis, myopathies or rhabdomolysis).
• Any current or relevant previous history of serious, severe or unstable physical or psychiatric illness, any medical disorder that may make the participant unlikely to fully complete the study, or any condition that presents undue risk from the study medication or procedures (e.g. malignant neoplasia).
• Active infectious disease of any nature, including clinically active viral infections.
• Laboratory Parameters

The following blood screening tests will result in exclusion from participation:

• Platelet count < 100 x 109 /L.
• Hemoglobin < 7.0 mmol/L.
• Liver function disturbances (bilirubin >2.50 x normal, transaminases >3 x ULN).
• CPK > 3 x ULN.
• Creatinine > 3 x ULN.