Duration of Effect of Alipogene Tiparvovec Treatment, Which Was Administered in Other Studies

NCT01447901 | Terminated

• 1 other identifier: CT-AMT-011-04
• Study Type: observational
• Target: 19
• Locations: 1 country
• Sites: 1

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.

Conditions

Hyperlipoproteinemia Type I

Keywords

Hyperlipoproteinemia Type I

Outcome Measures

Primary Outcomes (1)

• Composite of Pharmacodynamics

  Peak level, time-to-peak, and area under the curve (AUC) for tracer in plasma and chylomicron (CM) fraction to assess metabolism of newly-formed CMs in LPLD subjects previously treated with alipogene tiparvovec and to compare with untreated LPLD subjects and healthy controls.

  pre dose, 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 12, 24 hours post dose

Secondary Outcomes (9)

• Triglyceride (TG)-rich lipoproteins

  pre dose, 0, 1, 2, 3, 4, 4, 6, 7, 8, 9, 12, 24 hours post dose

• Glucose

  pre dose, 0, 2, 3, 4, 5, 6, 7, 8, 9, 12, 24 hours post dose

• Adverse Events (AE)

  Up to 21 days. Serious AEs will be followed to their resolution.

• Laboratory tests

  Up to 21 days

• Vital signs

  Up to 21 days

Study Arms (3)

previously treated LPLD Cohort

Subjects in Cohort 1 (previously treated LPLD Cohort) must have received AMT-011 during Studies CT-AMT-011-01 or -02

untreated LPLD control Cohort

Subjects in Cohort 2 (untreated LPLD control Cohort)) may have completed study PREPARATION-02 or known patients with genetically confirmed LPLD

normal healthy control Cohort

Volunteers in Cohort 3 (normal healthy control Cohort) must not have LPLD

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

* Lipoprotein Lipase Deficiency (LPLD) Patients * Healthy volunteers (community sample)

You may qualify if:

• Has provided signed informed consent.
• Male or female aged 18 to 70 years, inclusive at the time of consent.
• Females of childbearing potential must have a negative serum pregnancy test and agree to use a medically acceptable effective form of birth control from screening through Day 21 visit.
• Subjects in Cohort 1 (previously treated LPLD Cohort) must have received AMT-011 during Studies CT-AMT-011-01 or -02 as verified by site personnel.
• Subjects in Cohort 2 (untreated LPLD control Cohort)) may have completed study PREPARATION-02 as verified by site personnel or known patients with genetically confirmed LPLD.
• Volunteers in Cohort 3 (normal healthy control Cohort) must not have LPLD.
• Subjects 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 study.
• Must be able to communicate fully and effectively with the study personnel.

You may not qualify if:

• Female subjects who have a positive serum pregnancy test or who are nursing.
• Known allergy to any of the constituents of the radiolabeled meal/radio labeled agent, or a history of severe allergic or anaphylactic reactions.
• Investigator-determined clinically significant disease (other than LPLD for those subjects with LPLD), that would affect the subject's participation in the study.
• Healthy Volunteers with a history or presence of neurological, haematological, psychiatric, gastrointestinal, pulmonary, or other conditions known to interfere with the absorption, distribution, metabolism, or excretion of drugs, including plasma lipids out side normal range for age and gender and a body mass index (BMI) \>30.
• 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.
• A laboratory value at screening outside the normal range unless it is judged by the investigator as not clinically significant after appropriate evaluation.
• Clinically significant ECG at screening as determined by the investigator.
• Blood donations (≥1 unit) during the 2 months preceding and following the study or other significant blood loss.
• Other unspecified reasons that, in the opinion of the investigator or sponsor, make the subject unsuitable for enrolment.
• Any individual involved in the planning or conduct of this study. -

Sponsors & Collaborators

• Amsterdam Molecular Therapeutics: lead
• ICON plc: collaborator

Study Sites (1)

ECOGENE-21 Clinical Trial Center

Chicoutimi, Quebec, G7H 7P2, Canada

Location

Related Publications (11)

• Bickerton AS, Roberts R, Fielding BA, Hodson L, Blaak EE, Wagenmakers AJ, Gilbert M, Karpe F, Frayn KN. Preferential uptake of dietary Fatty acids in adipose tissue and muscle in the postprandial period. Diabetes. 2007 Jan;56(1):168-76. doi: 10.2337/db06-0822.

  PMID: 17192479 BACKGROUND

• Black DM, Sprecher DL. Dietary treatment and growth of hyperchylomicronemic children severely restricted in dietary fat. Am J Dis Child. 1993 Jan;147(1):60-2. doi: 10.1001/archpedi.1993.02160250062018.

  PMID: 8418601 BACKGROUND

• Chait A, Brunzell JD. Chylomicronemia syndrome. Adv Intern Med. 1992;37:249-73.

  PMID: 1557997 BACKGROUND

• Fortson MR, Freedman SN, Webster PD 3rd. Clinical assessment of hyperlipidemic pancreatitis. Am J Gastroenterol. 1995 Dec;90(12):2134-9.

  PMID: 8540502 BACKGROUND

• Miles JM, Park YS, Walewicz D, Russell-Lopez C, Windsor S, Isley WL, Coppack SW, Harris WS. Systemic and forearm triglyceride metabolism: fate of lipoprotein lipase-generated glycerol and free fatty acids. Diabetes. 2004 Mar;53(3):521-7. doi: 10.2337/diabetes.53.3.521.

  PMID: 14988233 BACKGROUND

• Normand-Lauziere F, Frisch F, Labbe SM, Bherer P, Gagnon R, Cunnane SC, Carpentier AC. Increased postprandial nonesterified fatty acid appearance and oxidation in type 2 diabetes is not fully established in offspring of diabetic subjects. PLoS One. 2010 Jun 4;5(6):e10956. doi: 10.1371/journal.pone.0010956.

  PMID: 20532041 BACKGROUND

• Rip J, Nierman MC, Ross CJ, Jukema JW, Hayden MR, Kastelein JJ, Stroes ES, Kuivenhoven JA. Lipoprotein lipase S447X: a naturally occurring gain-of-function mutation. Arterioscler Thromb Vasc Biol. 2006 Jun;26(6):1236-45. doi: 10.1161/01.ATV.0000219283.10832.43. Epub 2006 Mar 30.

  PMID: 16574898 BACKGROUND

• Rip J, Nierman MC, Sierts JA, Petersen W, Van den Oever K, Van Raalte D, Ross CJ, Hayden MR, Bakker AC, Dijkhuizen P, Hermens WT, Twisk J, Stroes E, Kastelein JJ, Kuivenhoven JA, Meulenberg JM. Gene therapy for lipoprotein lipase deficiency: working toward clinical application. Hum Gene Ther. 2005 Nov;16(11):1276-86. doi: 10.1089/hum.2005.16.1276.

  PMID: 16259561 BACKGROUND

• Ross CJ, Twisk J, Bakker AC, Miao F, Verbart D, Rip J, Godbey T, Dijkhuizen P, Hermens WT, Kastelein JJ, Kuivenhoven JA, Meulenberg JM, Hayden MR. Correction of feline lipoprotein lipase deficiency with adeno-associated virus serotype 1-mediated gene transfer of the lipoprotein lipase S447X beneficial mutation. Hum Gene Ther. 2006 May;17(5):487-99. doi: 10.1089/hum.2006.17.487.

  PMID: 16716106 BACKGROUND

• Santamarina-Fojo S. The familial chylomicronemia syndrome. Endocrinol Metab Clin North Am. 1998 Sep;27(3):551-67, viii. doi: 10.1016/s0889-8529(05)70025-6.

  PMID: 9785052 BACKGROUND

• Wittrup HH, Tybjaerg-Hansen A, Nordestgaard BG. Lipoprotein lipase mutations, plasma lipids and lipoproteins, and risk of ischemic heart disease. A meta-analysis. Circulation. 1999 Jun 8;99(22):2901-7. doi: 10.1161/01.cir.99.22.2901.

  PMID: 10359734 BACKGROUND

Related Links

• Homepage Sponsor

Biospecimen

Retention: SAMPLES WITH DNA

whole blood, serum, urine, faeces

MeSH Terms

Conditions

Hyperlipoproteinemia Type I

Condition Hierarchy (Ancestors)

Lipid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hyperlipoproteinemias; Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Daniel Gaudet, MD PhD

  ECOGENE-21 Clinical Trial Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 28, 2011
• First Posted: October 6, 2011
• Study Start: September 1, 2011
• Primary Completion: September 1, 2012
• Study Completion: September 1, 2012
• Last Updated: March 30, 2015

Record last verified: 2015-03

Locations

CA (1)