Status:

COMPLETED

A Safety and Efficacy Study of AEGR-733 to Treat Homozygous Familial Hypercholesterolemia (FH)

Lead Sponsor:

Aegerion Pharmaceuticals, Inc.

Collaborating Sponsors:

FDA Office of Orphan Products Development

Conditions:

Homozygous Familial Hypercholesterolemia

Eligibility:

All Genders

18+ years

Phase:

PHASE3

Brief Summary

The goal of this trial is to study the effects of AEGR-733 on LDL cholesterol, other lipids as well as measures of safety over the long-term.

Detailed Description

Homozygous familial hypercholesterolemia (FH) is a serious life-threatening genetic disease. Total plasma cholesterol levels are generally over 500 mg/dl and markedly premature cardiovascular disease ...

Eligibility Criteria

Inclusion

  • Males and females at least 18 years of age
  • Diagnosis of functional homozygous FH by at least one (a-c) of the following clinical criteria:
  • documented functional mutation(s) in both LDL receptor alleles or alleles known to affect LDL receptor functionality OR
  • skin fibroblast LDL receptor activity less than 20% normal OR
  • untreated TC greater than 500 mg/dL AND TG less then 300 mg/dL AND both parents have documented TC greater than 250 mg/dL
  • Concurrent lipid lowering medication/apheresis must be stable for at least 6 weeks before the baseline visit and must remain stable for the first 26 weeks.
  • Body weight at least 40 kg and less than 136 kg
  • Negative screening pregnancy test if female of child-bearing potential (females of child-bearing potential and all males must be following a medically accepted form of contraception)
  • Subjects must be willing to comply with all study-related procedures

Exclusion

  • Uncontrolled hypertension
  • History of chronic renal insufficiency
  • History of biopsy proven cirrhosis or abnormal LFTs at screening (AST or ALT greater than 2 x upper limit of normal and/or Total Bilirubin greater than or equal to 1.5 mg/dl unless patient has unconjugated hyperbilirubinemia due to Gilbert's syndrome)
  • Chronic hepatitis B or chronic hepatitis C
  • Any major surgical procedure occurring less than 3 months prior to the screening visit
  • Cardiac insufficiency defined by the NYHA classification as functional Class III or Class IV
  • Previous organ transplantation
  • History of a non-skin malignancy within the previous 3 years
  • Male subjects reporting more than 2 drinks per day or females reporting more than 1 drink per day (1 drink= 12 oz beer, 1 oz hard liquor, 5 oz wine).
  • Participation in an investigational drug study within 6 weeks prior to the screening visit
  • Known significant gastrointestinal bowel disease or malabsorption such as inflammatory bowel disease or chronic pancreatitis requiring use of daily pancreatic enzymes.
  • Serious or unstable medical or psychological conditions that, in the opinion of the investigator, would compromise the subject's safety or successful participation in the study.
  • Certain prohibited medications known to be potentially hepatotoxic, especially those that can induce microvesicular or macrovesicular steatosis. These include but are not limited to: accutane, amiodarone, heavy acetaminophen use (4g/day greater than 3 x q week), methotrexate, tetracyclines,and tamoxifen
  • Documented diagnosis of any of the following pulmonary conditions: Asthma, Chronic Obstructive Pulmonary Disease (COPD), Idiopathic pulmonary fibrosis
  • Documented diagnosis of any of the following liver diseases: Nonalcoholic Steatohepatitis, Alcoholic liver disease, Autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis, Wilson's disease, hemochromatosis, alpha 1 anti-trypsin deficiency.
  • Current use of corticosteroids or betaine

Key Trial Info

Start Date :

December 1 2007

Trial Type :

INTERVENTIONAL

Allocation :

ACTUAL

End Date :

October 1 2011

Estimated Enrollment :

29 Patients enrolled

Trial Details

Trial ID

NCT00730236

Start Date

December 1 2007

End Date

October 1 2011

Last Update

March 20 2018

Active Locations (10)

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Page 1 of 3 (10 locations)

1

Cedars-Sinai Medical Center

Los Angeles, California, United States, 90048

2

University of Pennsylvania

Philadelphia, Pennsylvania, United States, 19104

3

Robarts Research Institute

London, Ontario, Canada, N6A 5K8

4

Lipid Clinic and University of Montreal Community Genomic Medicine Center

Chicoutimi, Quebec, Canada, G7H 5H6