HepNet Pilot Trial: Multicenter Trial for the Treatment of Chronic Hepatitis E With Sofosbuvir (SofE)

Inclusion criteria

• Willing and able to provide written informed consent
• Male or female, age ≥ 18 years
• 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
• Documented previous ribavirin therapy or documented contraindication for full dose (≥ 600mg qd) ribavirin monotherapy for at least 3 months
• Body mass index (BMI) ≥ 18 kg/m2
• Screening ECG without clinically significant abnormalities
• 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)
• Subject has not been treated with any investigational drug or device within 42 days of the Screening visit
• 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
• 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

• 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.
• Ribavirin administration within the last 28 days.
• Infection with the hepatitis C virus (defined as HCV RNA positive)
• Gastrointestinal disorder or post-operative condition that could interfere with the absorption of the study drug (for example, gastric bypass or severe ulcerative colitis).
• Difficulty with blood collection and/or poor venous access for the purposes of phlebotomy.
• 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.
• Significant drug allergy (such as anaphylaxis or hepatotoxicity).
• Pregnant or nursing female
• 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.
• 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.

• Known hypersensitivity to SOF or formulation excipients.