Simvastatin for the Treatment of Chronic Hepatitis B

A Pilot Trial of Simvastatin Alone and Added to Tenofovir or Entecavir for the Treatment of Chronic Hepatitis B

The investigators have shown robust in vitro anti-hepatitis B activity of simvastatin alone and synergistic activity with all four FDA-approved anti-hepatitis B oral drugs tested. The investigators propose phase 1 studies in 48 chronic hepatitis B human carriers who have never been treated before. Doses of drugs will remain at or below FDA-approved dosage levels for cholesterol lowering (simvastatin) or hepatitis B (tenofovir or entecavir). Arm 1 will have simvastatin monotherapy only. Arm 2 will combine simvastatin with tenofovir. Arm 3 will combine simvastatin with entecavir. For maximum safety, the 3 arms and the dose groups in each arm will be filled consecutively and not concurrently. The definition of efficacy for simvastatin alone will be a 1 log drop of hepatitis B virus in 14 days. Efficacy for combination of drugs will require a 2 log drop of hepatitis B virus in 14 days. Numerous safety tests and stop rules are noted in the protocol.

Inclusion Criteria:

1. Hepatitis B positive by HBV DNA within 180 days.
2. Ages 18-70.
3. Men and non-pregnant women eligible.
4. Veteran's eligibility or appropriate health insurance.

Exclusion Criteria:

1. Use of any anti-HBV medicine within 30 days.
2. Decompensated cirrhosis as evidenced by esophageal varices, ascites, or encephalopathy. (grade 1 varices without history of bleeding will be allowed, if patient meets Child's-Pugh functional classification grade A).
3. A positive urine test for marijuana or alcohol within 2 months of screening.(Allowed to repeat tests on different days, if positive first time in order to become eligible for study.
4. Severe cardiovascular disease (ejection fraction <20%)* or uncontrolled angina.
5. Severe pulmonary disease (FEV1 < 1.0).
6. Chronic renal insufficiency (creatinine clearance <50 ml/min.
7. HIV positive patients.