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

This is an interventional treatment trial for Homozygous Familial Hypercholesterolemia Read More

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