Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00730236
Recruitment Status : Completed
First Posted : August 8, 2008
Results First Posted : February 22, 2013
Last Update Posted : March 20, 2018
Sponsor:
Collaborator:
FDA Office of Orphan Products Development
Information provided by (Responsible Party):
Aegerion Pharmaceuticals, Inc.

Tracking Information
First Submitted Date  ICMJE August 6, 2008
First Posted Date  ICMJE August 8, 2008
Results First Submitted Date  ICMJE January 18, 2013
Results First Posted Date  ICMJE February 22, 2013
Last Update Posted Date March 20, 2018
Study Start Date  ICMJE December 2007
Actual Primary Completion Date September 2010   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 15, 2014)
Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) [ Time Frame: Baseline and Week 26 ]
Percent change from Baseline in LDL-C
Original Primary Outcome Measures  ICMJE
 (submitted: August 7, 2008)
LDL cholesterol [ Time Frame: 26 weeks ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 15, 2014)
  • Percent Change From Baseline in Total Cholesterol (TC) [ Time Frame: Baseline and Week 26 ]
    Percent change from Baseline in TC
  • Percent Change From Baseline for Apolipoprotein B (Apo B) [ Time Frame: Baseline and Week 26 ]
    Percent change from Baseline for Apo B
  • Percent Change From Baseline in Triglycerides [ Time Frame: Baseline and Week 26 ]
    Percent change from Baseline in triglycerides
  • Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) [ Time Frame: Baseline and Week 26 ]
    Percent change from Baseline in HDL-C
  • Percent Change From Baseline in Non-HDL-C [ Time Frame: Baseline and Week 26 ]
    Percent change from Baseline in non-HDL-C
  • Percent Change From Baseline in Apolipoprotein AI (Apo AI) [ Time Frame: Baseline and Week 26 ]
    Percent change from Baseline in Apo AI
  • Absolute Change From Baseline in Hepatic Fat Percent [ Time Frame: Baseline and Week 78 ]
    Absolute change from Baseline in hepatic fat percent
  • Absolute Change From Baseline in Alanine Aminotransferase (ALT) [ Time Frame: Baseline and Week 78 ]
    Absolute change from Baseline in ALT
  • Absolute Change From Baseline in Aspartate Aminotransferase (AST) [ Time Frame: Baseline and Week 78 ]
    Absolute change from Baseline in AST
  • Absolute Change From Baseline in Total Bilirubin [ Time Frame: Baseline and Week 78 ]
    Absolute change from Baseline in total bilirubin
  • Absolute Change From Baseline in Weight [ Time Frame: Baseline and Week 78 ]
    Absolute change from Baseline in weight
Original Secondary Outcome Measures  ICMJE
 (submitted: August 7, 2008)
  • Total cholesterol, HDL cholesterol, Triglycerides, apolipoproteins B and AI [ Time Frame: Up to 1.5 yr ]
  • Hepatic (liver) fat as determined by MRI/NMRS [ Time Frame: Up to 1.5 yrs ]
  • Pharmacokinetics [ Time Frame: Up to 1.5 yrs ]
  • Adverse events, labs and weight [ Time Frame: Up to 1.5 yrs ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Safety and Efficacy Study of AEGR-733 to Treat Homozygous Familial Hypercholesterolemia (FH)
Official Title  ICMJE A Phase III Study of Microsomal Triglyceride Transfer Protein (MTP) Inhibitor AEGR-733 in Patients With Homozygous Familial Hypercholesterolemia on Current Lipid-lowering Therapy
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 is the major consequence. Untreated, most patients develop atherosclerosis before age 20 and generally do not survive past age 30. The primary goal of therapy involves reducing cholesterol (specifically, LDL cholesterol) and preventing coronary artery disease. Unfortunately, patients with homozygous FH are minimally responsive or unresponsive to available drug therapy and thus there are limited treatment options. The current standard of care is LDL apheresis, a physical method of removing the plasma of LDL cholesterol which can transiently reduce cholesterol by more than 50%. However, there is rapid re-accumulation of LDL cholesterol in plasma, and therefore apheresis has to be repeated frequently (every 1-2 weeks) and requires 2 separate sites for IV access. Although anecdotally this procedure may delay the onset of atherosclerosis, it is laborious, expensive, and not readily available. Furthermore, although it is a procedure that is generally well tolerated, the fact that it needs frequent repetition and IV access can be challenging for many of these young patients. Therefore, there is a tremendous unmet medical need for new medical therapies for this orphan disease.

AEGR-733 is a novel oral therapeutic agent for hypercholesterolemia. Its mechanism involves inhibition of microsomal triglyceride transfer protein, resulting in a reduction of LDL cholesterol. Earlier studies in patients with homozygous FH reveal AEGR-733 is highly effective in lowering LDL cholesterol, yet long term safety and efficacy need to be established.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Homozygous Familial Hypercholesterolemia
Intervention  ICMJE Drug: AEGR-733
5-80 mg daily by mouth for 1.5 yrs
Other Names:
  • lomitapide
  • BMS-201038
Study Arms  ICMJE Experimental: AEGR-733
Intervention: Drug: AEGR-733
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: February 25, 2012)
29
Original Estimated Enrollment  ICMJE
 (submitted: August 7, 2008)
20
Actual Study Completion Date  ICMJE October 2011
Actual Primary Completion Date September 2010   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Males and females at least 18 years of age
  2. 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
  3. 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.
  4. Body weight at least 40 kg and less than 136 kg
  5. 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)
  6. Subjects must be willing to comply with all study-related procedures

Exclusion Criteria:

  1. Uncontrolled hypertension
  2. History of chronic renal insufficiency
  3. 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)
  4. Chronic hepatitis B or chronic hepatitis C
  5. Any major surgical procedure occurring less than 3 months prior to the screening visit
  6. Cardiac insufficiency defined by the NYHA classification as functional Class III or Class IV
  7. Previous organ transplantation
  8. History of a non-skin malignancy within the previous 3 years
  9. 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).
  10. Participation in an investigational drug study within 6 weeks prior to the screening visit
  11. Known significant gastrointestinal bowel disease or malabsorption such as inflammatory bowel disease or chronic pancreatitis requiring use of daily pancreatic enzymes.
  12. 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.
  13. 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
  14. Documented diagnosis of any of the following pulmonary conditions: Asthma, Chronic Obstructive Pulmonary Disease (COPD), Idiopathic pulmonary fibrosis
  15. 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.
  16. Current use of corticosteroids or betaine
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   Italy,   South Africa,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00730236
Other Study ID Numbers  ICMJE AEGR-733-005 / UP1002
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Aegerion Pharmaceuticals, Inc.
Study Sponsor  ICMJE Aegerion Pharmaceuticals, Inc.
Collaborators  ICMJE FDA Office of Orphan Products Development
Investigators  ICMJE
Study Director: Mark Sumeray, MD Aegerion Pharmaceuticals, Inc.
Principal Investigator: Marina Cuchel, MD, PhD Univerity of Pennsylvania
PRS Account Aegerion Pharmaceuticals, Inc.
Verification Date January 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP