NCT00891306

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 possible mechanisms of action of the therapy.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
5

participants targeted

Target at below P25 for phase_2

Timeline
Completed

Started Feb 2009

Geographic Reach
1 country

2 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

February 1, 2009

Completed
3 months until next milestone

First Submitted

Initial submission to the registry

April 30, 2009

Completed
1 day until next milestone

First Posted

Study publicly available on registry

May 1, 2009

Completed
1.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 1, 2010

Completed
8 months until next milestone

Study Completion

Last participant's last visit for all outcomes

April 1, 2011

Completed
Last Updated

September 29, 2011

Status Verified

September 1, 2011

Enrollment Period

1.5 years

First QC Date

April 30, 2009

Last Update Submit

September 28, 2011

Conditions

Familial Lipoprotein Lipase Deficiency

Keywords

LPLD, Lipoprotein Lipase DeficiencyChylomicronemiaGene therapyAAVLipoprotein LipaseAlipogene tiparvovecAMT-011

Outcome Measures

Primary Outcomes (1)

  • Reduction of triglyceride (TG) concentrations

    12 weeks

Secondary Outcomes (4)

  • Reduction of chylomicrons and/or chylomicron-TG ratio

    12 weeks

  • To determine the biological activity and expression of the lipoprotein lipase [LPLS447X] transgene product

    14 weeks

  • To assess the safety profile

    14 weeks

  • To assess shedding of viral vector

    14 weeks

Study Arms (1)

Treatment arm

EXPERIMENTAL

Gene Therapy

Genetic: Alipogene Tiparvovec (AMT-011), Human LPL [S447X]Drug: mycophenolate mofetilDrug: cyclosporineDrug: methylprednisolone

Interventions

Alipogene Tiparvovec (AMT-011), Human LPL [S447X]GENETIC

intra muscular, 1 x E12 gc per kg body weight, injected in a single series of intramuscular injections

Also known as: Glybera, AMT-011
Treatment arm
mycophenolate mofetilDRUG

oral, 2 g/day, day -3 till week 12

Also known as: CellCept
Treatment arm
cyclosporineDRUG

oral, 3 mg/kg/day, day -3 till week 12

Also known as: Neoral
Treatment arm
methylprednisoloneDRUG

single intravenous bolus of methylprednisolone (1 mg/kg bodyweight)

Also known as: Solumedrol®
Treatment arm

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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
  • +4 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

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

Chicoutimi, Quebec, G7H 5H6, Canada

Location

Centre des Maladies Lipidiques de Québec

Québec, Quebec, G1V 4M6, Canada

Location

Related Publications (6)

  • 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: 16259561BACKGROUND

  • Ross CJ, Twisk J, Meulenberg JM, Liu G, van den Oever K, Moraal E, Hermens WT, Rip J, Kastelein JJ, Kuivenhoven JA, Hayden MR. Long-term correction of murine lipoprotein lipase deficiency with AAV1-mediated gene transfer of the naturally occurring LPL(S447X) beneficial mutation. Hum Gene Ther. 2004 Sep;15(9):906-19. doi: 10.1089/hum.2004.15.906.

    PMID: 15353045BACKGROUND

  • Ross CJ, Liu G, Kuivenhoven JA, Twisk J, Rip J, van Dop W, Excoffon KJ, Lewis SM, Kastelein JJ, Hayden MR. Complete rescue of lipoprotein lipase-deficient mice by somatic gene transfer of the naturally occurring LPLS447X beneficial mutation. Arterioscler Thromb Vasc Biol. 2005 Oct;25(10):2143-50. doi: 10.1161/01.ATV.0000176971.27302.b0. Epub 2005 Jul 7.

    PMID: 16002740BACKGROUND

  • 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: 16716106BACKGROUND

  • Stroes ES, Nierman MC, Meulenberg JJ, Franssen R, Twisk J, Henny CP, Maas MM, Zwinderman AH, Ross C, Aronica E, High KA, Levi MM, Hayden MR, Kastelein JJ, Kuivenhoven JA. Intramuscular administration of AAV1-lipoprotein lipase S447X lowers triglycerides in lipoprotein lipase-deficient patients. Arterioscler Thromb Vasc Biol. 2008 Dec;28(12):2303-4. doi: 10.1161/ATVBAHA.108.175620. Epub 2008 Sep 18. No abstract available.

    PMID: 18802015BACKGROUND

  • Carpentier AC, Frisch F, Labbe SM, Gagnon R, de Wal J, Greentree S, Petry H, Twisk J, Brisson D, Gaudet D. Effect of alipogene tiparvovec (AAV1-LPL(S447X)) on postprandial chylomicron metabolism in lipoprotein lipase-deficient patients. J Clin Endocrinol Metab. 2012 May;97(5):1635-44. doi: 10.1210/jc.2011-3002. Epub 2012 Mar 21.

    PMID: 22438229DERIVED

Related Links

MeSH Terms

Conditions

Hyperlipoproteinemia Type I

Interventions

Alipogene tiparvovecMycophenolic AcidCyclosporineMethylprednisoloneMethylprednisolone Hemisuccinate

Condition Hierarchy (Ancestors)

Lipid Metabolism, Inborn ErrorsMetabolism, Inborn ErrorsGenetic Diseases, InbornCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesHyperlipoproteinemiasHyperlipidemiasDyslipidemiasLipid Metabolism DisordersMetabolic DiseasesNutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

CaproatesAcids, AcyclicCarboxylic AcidsOrganic ChemicalsFatty AcidsLipidsCyclosporinsPeptides, CyclicMacrocyclic CompoundsPolycyclic CompoundsPeptidesAmino Acids, Peptides, and ProteinsPrednisolonePregnadienetriolsPregnadienesPregnanesSteroidsFused-Ring Compounds

Study Officials

  • Daniel Gaudet, MD, Ph.D.

    ECOGENE-21 Clinical Trial Center / Centre de santé et de services sociaux de Chicoutimi, Chicoutimi Hospital, Quebec, Canada

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

April 30, 2009

First Posted

May 1, 2009

Study Start

February 1, 2009

Primary Completion

August 1, 2010

Study Completion

April 1, 2011

Last Updated

September 29, 2011

Record last verified: 2011-09

Locations

CA(2)