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

Inclusion Criteria

• 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 Criteria

• 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