HepNet Pilot Trial: Multicenter Trial for the Treatment of Chronic Hepatitis E With Sofosbuvir (SofE)
HepNet Pilot Trial: Multicenter Trial for the Treatment of Chronic Hepatitis E With Sofosbuvir (SofE)
This is a single arm multicenter pilot study to provide preliminary evidence whether
 sofosbuvir (SOF) is efficacious and can be safely used in patients with chronic Hepatitis E
 virus infection.
Inclusion Criteria:

 1. Willing and able to provide written informed consent

 2. Male or female, age ≥ 18 years

 3. Confirmation of chronic HEV infection documented by: Positive HEV RNA at least 3
 months before Screening, and positive for HEV RNA at the time of Screening

 4. Documented previous ribavirin therapy or documented contraindication for full dose (≥
 600mg qd) ribavirin monotherapy for at least 3 months

 5. Body mass index (BMI) ≥ 18 kg/m2

 6. Screening ECG without clinically significant abnormalities

 7. Subjects must have the following laboratory parameters at screening:

 -  Platelets ≥ 60,000/μL

 -  INR ≤2.0 x ULN unless subject has known hemophilia or is stable on an
 anticoagulant regimen affecting INR

 -  HbA1c ≤ 10%

 -  Creatinine clearance (CLcr) ≥ 30 mL/min, as calculated by the Cockcroft-Gault
 equation (using actual body weight)

 8. Subject has not been treated with any investigational drug or device within 42 days of
 the Screening visit

 9. A negative serum pregnancy test is required for female subjects (unless surgically
 sterile or women ≥ 54 years of age with cessation for 24 ≥ months of previously
 occurring menses).

 Complete abstinence from intercourse. Periodic abstinence (e.g., calendar, ovulation,
 symptothermal, post-ovulation methods) is not permitted.

 Or

 Consistent and correct use of 1 of the following methods of birth control listed
 below, in addition to a male partner who correctly uses a condom, from the date of
 Screening until 30 days after last dose of study drug:

 -  intrauterine device (IUD) with a failure rate of < 1% per year

 -  female barrier method: cervical cap or diaphragm with spermicidal agent

 -  tubal sterilization

 -  vasectomy in male partner

 -  hormone-containing contraceptive:

 -  implants of levonorgestrel

 -  injectable progesterone

 -  oral contraceptives (either combined or progesterone only)

 -  contraceptive vaginal ring

 -  transdermal contraceptive patch

 10. Subject must be able to comply with the dosing instructions for study drug
 administration and be able to complete the study schedule of assessments.

 Exclusion Criteria:

 1. Clinically-significant illness (other than HEV) or any other major medical disorder
 that, in the opinion of the investigator, may interfere with subject treatment,
 assessment or compliance with the protocol.

 2. Ribavirin administration within the last 28 days.

 3. Infection with the hepatitis C virus (defined as HCV RNA positive)

 4. Gastrointestinal disorder or post-operative condition that could interfere with the
 absorption of the study drug (for example, gastric bypass or severe ulcerative
 colitis).

 5. Difficulty with blood collection and/or poor venous access for the purposes of
 phlebotomy.

 6. Psychiatric hospitalization, suicide attempt, and/or a period of disability as a
 result of their psychiatric illness within the last 2 years. Subjects with psychiatric
 illness that is wellcontrolled on a stable treatment regimen for at least 12 months
 prior to screening or has not required medication in the last 12 months may be
 included.

 7. Significant drug allergy (such as anaphylaxis or hepatotoxicity).

 8. Pregnant or nursing female

 9. Clinically-relevant drug or alcohol abuse within 12 months of screening including any
 uncontrolled drug use within 6 months of screening. A positive drug screen will
 exclude subjects unless it can be explained by a prescribed medication; the diagnosis
 and prescription must be approved by the investigator. Uncontrolled users of
 intravenous drugs will not be permitted to enroll in the study.

 10. Use of any prohibited concomitant medications within 21 days of the Baseline/Day 1
 visit.

 Use of Amiodaron as concomitant medication is prohibited within 60 days of
 Baseline/Day1 visit.

 11. Known hypersensitivity to SOF or formulation excipients.