Ignite Creation Date:
2024-05-05 @ 11:55 PM
Last Modification Date:
2024-10-26 @ 10:41 AM
Study NCT ID:
NCT01447901
Status:
TERMINATED
Last Update Posted:
2015-03-30
First Post:
2011-09-28
Brief Title:
Duration of Effect of Alipogene Tiparvovec Treatment Which Was Administered in Other Studies
Sponsor:
Amsterdam Molecular Therapeutics
Organization:
Amsterdam Molecular Therapeutics
Study Overview
Official Title:
Prospective Non-interventional Non-randomised Open-label Adult Study to Assess the Long Term Biological Therapeutic Response to Alipogene Tiparvovec in Lipoprotein Lipase Deficiency LPLD and Comparing Postprandial Chylomicron Metabolism Following a Radiolabeled Meal in LPLD Subjects Previously Treated With Alipogene Tiparvovec Studies CT-AMT-011-01 or -02 to Untreated LPLD Subjects Study PREPARATION-02 and to Healthy Volunteers
Status:
TERMINATED
Status Verified Date:
2015-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Business reason
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
LPL Lipoprotein Lipase is an enzyme which plays an important role in the elimination of triglycerides fat and the clearance of dietary fat particles known as chylomicrons CM in the blood In patients who have an abnormal LPL gene the enzyme does not work total hereditary LPL deficiency which results in a large increase in the amount of triglycerides fats and chylomicrons in the blood This increases the risk of inflammation in the pancreas and leads to long term negative effects for bloods vessels atherosclerosis Current medications and or a strict and low fat diet do not sufficiently reduce the level of triglycerides in order to prevent these conditions To solve this problem the company AMT is developing a gene therapy AMT-011
In normal healthy individuals fat particles are rapidly cleared from the circulation following a standard meal Within approximately 3 hours the highest levels of fat is reached and clearance is achieved within the subsequent 9 hours In LPLD subjects the clearance of fat is greatly reduced as a direct consequence of the lack of LPL During this study a standard meal with a tracer 3H-palmitate is given Since palmitate is incorporated in the dietary fat this study enabled monitoring of appearance of newly formed dietary fat into- and clearance of these newly formed dietary fats from the circulation over time
The principal aim of the study is to verify if the gene therapy AMT 011 is still effective in the treatment of this condition Systemic appearance and clearance of new formed dietary fat particles after ingestion of the meal will be determined by measuring the level of tracer at different time points
In normal healthy individuals fat particles are rapidly cleared from the circulation following a standard meal Within approximately 3 hours the highest levels of fat is reached and clearance is achieved within the subsequent 9 hours In LPLD subjects the clearance of fat is greatly reduced as a direct consequence of the lack of LPL During this study a standard meal with a tracer 3H-palmitate is given Since palmitate is incorporated in the dietary fat this study enabled monitoring of appearance of newly formed dietary fat into- and clearance of these newly formed dietary fats from the circulation over time
The principal aim of the study is to verify if the gene therapy AMT 011 is still effective in the treatment of this condition Systemic appearance and clearance of new formed dietary fat particles after ingestion of the meal will be determined by measuring the level of tracer at different time points
Detailed Description:
Lipoprotein lipase deficiency LPLD is a rare autosomal recessive inherited disorder caused by loss-of-function mutations in the lipoprotein lipase LPL gene It is the most common genetic cause of hyperchylomicronaemia a condition which results in continuous and excessively high levels of plasma chylomicrons CM and severe hypertriglyceridaemia Lipoprotein lipase normally mediates the hydrolysis of triglycerides TG in CMs and very low-density lipoproteins VLDL and thereby aids in the clearance of TG-rich lipoproteins and reduction of TGs in the circulation
Alipogene tiparvovec Glybera is in development for the therapy of LPLD In summary alipogene tiparvovec contains the human lipoprotein LPL gene variant LPLS447X in a non-replicating vector in solution administered in a one-time series of intramuscular injections in the armslegsThe aim of alipogene tiparvovec Glybera administration is to provide LPL activity and to stimulate CM metabolism in LPLD patients
To test the activity of LPL in subjects previously treated with alipogene tiparvovec in this study LPLD subjects will be given a radiolabeled meal supplemented with a labeled tracer 3H-palmitate Since dietary palmitate is incorporated into CMs as they are formed in the enterocytes of the gut this enables monitoring of the appearance and subsequent clearance of newly formed CMs from the circulation over time the so-called postprandial test The radiolabeled meal will be provided in a liquid form similar to a milkshake After ingestion of the radiolabeled meal level of radiolabel in the CM fraction at different time points prior to and during the postprandial phase will be measured and thus determine the appearance and clearance of CMs within the circulation
The principal aim of the study is to increase the understanding of how long alipogene tiparvovec may be effective in the treatment of LPLD To understand this 3 cohorts of subjects will be studied 1 Subjects with LPLD who have previously been treated with alipogene tiparvovec 2 Subjects with LPLD who have not been treated with alipogene tiparvovec and 3 Subjects who do not have LPLD healthy volunteers The subjects general state of health will also be monitored during the clinical study and the possible disadvantages associated with the postprandial test will be assessed
Alipogene tiparvovec Glybera is in development for the therapy of LPLD In summary alipogene tiparvovec contains the human lipoprotein LPL gene variant LPLS447X in a non-replicating vector in solution administered in a one-time series of intramuscular injections in the armslegsThe aim of alipogene tiparvovec Glybera administration is to provide LPL activity and to stimulate CM metabolism in LPLD patients
To test the activity of LPL in subjects previously treated with alipogene tiparvovec in this study LPLD subjects will be given a radiolabeled meal supplemented with a labeled tracer 3H-palmitate Since dietary palmitate is incorporated into CMs as they are formed in the enterocytes of the gut this enables monitoring of the appearance and subsequent clearance of newly formed CMs from the circulation over time the so-called postprandial test The radiolabeled meal will be provided in a liquid form similar to a milkshake After ingestion of the radiolabeled meal level of radiolabel in the CM fraction at different time points prior to and during the postprandial phase will be measured and thus determine the appearance and clearance of CMs within the circulation
The principal aim of the study is to increase the understanding of how long alipogene tiparvovec may be effective in the treatment of LPLD To understand this 3 cohorts of subjects will be studied 1 Subjects with LPLD who have previously been treated with alipogene tiparvovec 2 Subjects with LPLD who have not been treated with alipogene tiparvovec and 3 Subjects who do not have LPLD healthy volunteers The subjects general state of health will also be monitored during the clinical study and the possible disadvantages associated with the postprandial test will be assessed
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None