A Safety and Efficacy Study of AEGR-733 to Treat Homozygous Familial Hypercholesterolemia (FH)
Condition: Homozygous Familial Hypercholesterolemia
MeSH terms: Hyperlipoproteinemia Type II; Homozygous Familial Hypercholesterolemia; Hypercholesterolemia
Intervention: AEGR-733
Intervention description: 5-80 mg daily by mouth for 1.5 yrs
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 29.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

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.
    

Eligibility criteria:

        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