Adults with chronic Hepatitis E virus infection, who either failed to achieve clearance of infection after ribavirin therapy or have contraindications for ribavirin. MedDRA version: 20.1 Level: PT Classification code 10019768 Term: Hepatitis E System Organ Class: 10021881 - Infections and infestations
Conditions
Interventions
Trade Name: Sovaldi® 400 mg Filmtabletten
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: SOFOSBUVIR
CAS Number: 1190307-88-0
Other descriptive name: SOFOSBUVIR
Concentration unit: mg mil
Sponsors
Hannover Medical School
Eligibility
Sex/Gender
All
Inclusion criteria
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 =65 years) yes F.1.3.1 Number of subjects for this age range 1
Exclusion criteria
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 well-controlled 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/Day 1 visit. 11. Known hypersensitivity to SOF or formulation excipients.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • To evaluate the antiviral efficacy of sofosbuvir (SOF) against HEV as measured by the proportion of subjects who become HEV RNA negative (HEV RNA undetectable) after 24 weeks of therapy • To evaluate the safety and tolerability of SOF-containing regimens administered for up to 24 weeks in patients with chronic HEV infection ;Secondary Objective: • To evaluate if SOF has an antiviral activity against HEV in patients with chronic hepatitis E determined by viral load declines after 2, 4, 7 (w1), 14 (w2), 28 (w4), 56 (w8), 84 (w12), 112 (w16), 140 (w20), and 168 (w24) days of treatment • To evaluate if rapid (>2log within 2 weeks of treatment), vs slow decline of HEV viral load has an influence on reaching HEV RNA negativity • To determine ALT normalization after 12 weeks and 24 weeks of therapy and 12 weeks after discontinuation of therapy (FU12 visit) • To determine the durability of response 12 weeks after discontinuation of therapy (HEV RNA negative) Assessment of safety: Adverse events (AEs) and safety laboratory tests will be collected throughout the study (up to 12 weeks after discontinuation of therapy, FU12). ;Primary end point(s): Proportion of subjects who become HEV RNA negative after 24 weeks of therapy;Timepoint(s) of evaluation of this end point: After 24 weeks of therapy | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Proportion of subjects who are HEV RNA negative 12 weeks after discontinuation of therapy 2. Additional efficacy evaluations include HEV RNA change from baseline during therapy 3. Comparison of proportion of patients who are HEV RNA negative after rapid or slow decline of HEV viral load after 24 weeks of therapy. 4. Proportion of subject who reached ALT normalization after 12 weeks and 24 weeks of therapy and 12 weeks after discontinuation of therapy (FU12 visit) 5. Assessment of safety: Adverse events (AEs) and safety laboratory tests will be collected throughout the study (up to 12 weeks after discontinuation of therapy, FU12). ;Timepoint(s) of evaluation of this end point: 1. 12 weeks after discontinuation of therapy 2. Throughout the study 3. After 24 weeks of therapy 4. 12 weeks and 24 weeks of therapy and 12 weeks after discontinuation of therapy 5. Throughout the study until 12 weeks after discontinuation of therapy | — |
Countries
Germany
Contacts
Public ContactProf. Dr. Markus Cornberg
Hannover Medical School
Outcome results
None listed