Ezetimibe as a Safe and Efficacious Treatment for Chronic Hepatitis C
Condition: Chronic Hepatitis C
MeSH terms: Hepatitis A; Hepatitis C; Hepatitis C, Chronic; Hepatitis; Hepatitis, Chronic
Intervention: 20mg ezetimibe; Placebo; 40mg ezetimibe
Intervention description: Participants assigned to this intervention will receive 20mg per day of ezetimibe for 12 weeks.; Participants assigned to this intervention will receive placebo every day for 12 weeks; Participants assigned to this intervention will receive 40mg per day of ezetimibe for 12 weeks.
Intervention MeSH terms: Ezetimibe
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 2.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No
Keywords: hepatitis C virus; antiviral treatment; viral entry inhibitor; mathematical modeling

Summary:

      To address the need for more affordable hepatitis C virus (HCV) antivirals with high barriers
      to viral resistance and strategies to shorten the current treatment duration, the goal is to
      develop affordable therapeutic regimens to prevent HCV entry/spread and test the efficacy of
      those inhibitors for treating HCV infection. The investigators recently discovered that a
      major cholesterol uptake receptor is required for HCV entry into hepatocytes and that there
      is already an FDA-approved drug that inhibits cholesterol uptake by this receptor.
      Importantly the same drug also potently blocks HCV entry in human liver cells both in cell
      culture and in a small animal model. Further, looking back at people who were previously
      treated for HCV infection, the investigators found treatment response to be better (i.e.
      larger viral log reduction) in patients who happened to be taking ezetimibe (EZE). Hence, the
      objective of this study is to assess whether the FDA-approved drug (ezetimibe) is useful for
      the treatment of chronic HCV. The investigators predict that when administered as monotherapy
      ezetimibe will reduce HCV viremia perhaps allowing for viral clearance and that when included
      in combination treatment regimens that EZE will increase HCV decline resulting in faster
      viral clearance (i.e. shorter/cheaper direct-acting antiviral [DAA] therapy). To test these
      hypotheses, the investigators will execute the following aims: (1) Assess the efficacy of EZE
      monotherapy in chronically HCV infected and predict time to cure; (2) Assess the efficacy of
      EZE as an adjunct therapy in chronically HCV infected patients undergoing currently approved
      HCV DAA treatment.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Males/females 18 - 70 yrs of age

          -  Serum HCV RNA >2,000 IU/ml

          -  Hepatitis C genotype 1

          -  Other causes of chronic liver disease excluded by appropriate clinical, laboratory, or
             histologic evaluation

          -  The following hematological criteria must be met:

               -  Hemoglobin > 12 g/dl

               -  Absolute neutrophil count (ANC) > 1.0x109 /L

               -  Platelets 150 x 108 /L (i.e normal)

          -  Serum creatinine <1.5 times the upper limit of normal (ULN) at screening.

          -  Fasting blood sugar normal for non-diabetics or hemoglobin A1C < 8.5% with diabetes

          -  Women of childbearing potential must have a negative pregnancy test prior to receiving
             treatment. Sexually active women must take adequate precautions to prevent pregnancy
             during the study. Pregnancy tests will be done at the final clinic visits and every 4
             weeks

          -  Patient provides written informed consent

        Exclusion Criteria:

          -  Evidence of liver disease other than HCV:

               -  Antinuclear antibodies (ANA) >1:160

               -  Active alcoholic liver disease.

               -  Hepatitis B surface antigen positive

               -  Hemochromatosis

               -  Wilson disease

               -  Alpha-1-antitrypsin deficiency

               -  Recent hepatotoxic drug exposure

               -  Cirrhosis with complications of portal hypertension including esophageal varices
                  (> grade 1 by endoscopy), ascites, or hepatic encephalopathy, or bilirubin >2.0
                  mg/dl

          -  Patients with advanced fibrosis (defined herein as decompensated cirrhosis, FIB4 >
             2.5, platelet count <150 x 103/uL, clinical or radiographic evidence of cirrhosis)

          -  Extrahepatic manifestations of liver disease or HIV co-infection

          -  Use of fibric acid, Fenofibrate or cholestyramine

          -  Active substance abuse including, but not limited to alcohol or i.v./inhaled drugs

          -  Use of chemotherapy or systemic steroid therapy within 30 days prior to enrollment

          -  Pregnancy, females who are breast feeding, or females of child bearing potential who
             are not using adequate birth control measures

          -  History of a medical condition that could interfere with participation or completion
             of the protocol

          -  Organ transplant recipient

          -  History of hypersensitivity to ezetimibe