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

NCT03282474 | Completed Phase 2

• 2 other identifiers: HepNet-SofE2017-000403-24
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Hepatitis E; Hepatitis Chronic Viral

Keywords

Hepatitis E

Outcome Measures

Primary Outcomes (1)

• Proportion of subjects who become HEV RNA negative after 24 weeks of therapy

  Measured by the proportion of subjects who become HEV RNA negative (HEV RNA undetectable)

  after 24 weeks of therapy

Secondary Outcomes (5)

• Proportion of subjects who are HEV RNA negative 12 weeks after discontinuation of therapy

  12 weeks after discontinuation of therapy (week 36)

• Additional efficacy evaluations include HEV RNA change from baseline during therapy

  after 2 days, 4 days, 1 week, 2 weeks, 4 weeks, 8 weeks, 12 weeks,16 weeks, 20 weeks, and 24 weeks of therapy

• Comparison of proportion of patients who are HEV RNA negative after rapid or slow decline of HEV viral load after 24 weeks of therapy

  after 24 weeks of therapy

• Proportion of subject who reached ALT normalization after 12 weeks and 24 weeks of therapy and 12 weeks after discontinuation of therapy

  after 12 and 24 weeks of therapy and 12 weeks after discontinuation of therapy (week 36)

• Assessment of safety: Adverse events and safety laboratory tests will be collected throughout the study

  through study completion, an average of 36 weeks

Study Arms (1)

Sofosbuvir

EXPERIMENTAL

Sofosbuvir 400 MG film-coated tablet, oral administration of one tablet once daily for 24 weeks.

Drug: Sofosbuvir

Interventions

Sofosbuvir DRUG

Sofosbuvir 400 MG Oral Tablet \[Sovaldi\]

Also known as: Sovaldi

Sofosbuvir

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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:

You may not qualify if:

• 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.

Sponsors & Collaborators

• Hannover Medical School: lead
• HepNet Study House, German Liverfoundation: collaborator
• Gilead Sciences: collaborator
• German Center for Infection Research: collaborator

Study Sites (3)

Hannover Medical School, Clinic for Gastroenterology, Hepatology, and Endocrinology

Hanover, Lower Saxony, 30625, Germany

Location

Charité, Campus Virchow-Klinikum, Medical Department, Division of Hepatology and Gastroenterology

Berlin, 13353, Germany

Location

University Medical Center Hamburg-Eppendorf, Center for Internal Medicine, I. Medical Clinic and Polyclinic

Hamburg, 20246, Germany

Location

Related Publications (3)

• Wahid A, Meyer N, Wundes C, Huffner L, Janshoff S, Frericks N, Friesland M, Dinkelborg K, Aliabadi E, Laue F, Cornberg M, Maasoumy B, Bremer B, Pischke S, Muller T, Wiesch JZS, Benckert J, Ulrich RG, Hardtke S, Dorge P, Vondran F, Lohse A, Manns MP, Todt D, Wedemeyer H, Pietschmann T, Steinmann E, Gomer A, Behrendt P. Extrahepatic Replication and Genomic Signatures of the Hepatitis E Virus in the Kidney. Liver Int. 2025 Jul;45(7):e70183. doi: 10.1111/liv.70183.

  PMID: 40575997 DERIVED

• Gomer A, Klohn M, Jagst M, Nocke MK, Pischke S, Horvatits T, Schulze Zur Wiesch J, Muller T, Hardtke S, Cornberg M, Wedemeyer H, Behrendt P, Steinmann E, Todt D. Emergence of resistance-associated variants during sofosbuvir treatment in chronically infected hepatitis E patients. Hepatology. 2023 Dec 1;78(6):1882-1895. doi: 10.1097/HEP.0000000000000514. Epub 2023 Jun 20.

  PMID: 37334496 DERIVED

• Cornberg M, Pischke S, Muller T, Behrendt P, Piecha F, Benckert J, Todt D, Steinmann E, Papkalla A, von Karpowitz M, Koch A, Lohse A, Hardtke S, Manns MP, Wedemeyer H. Sofosbuvir monotherapy fails to achieve HEV RNA elimination in patients with chronic hepatitis E - The HepNet SofE pilot study. J Hepatol. 2020 Sep;73(3):696-699. doi: 10.1016/j.jhep.2020.05.020. Epub 2020 Jul 2. No abstract available.

  PMID: 32624195 DERIVED

MeSH Terms

Conditions

Hepatitis E

Interventions

Sofosbuvir

Condition Hierarchy (Ancestors)

Hepatitis, Viral, Human; Virus Diseases; Infections; RNA Virus Infections; Hepatitis; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Uridine Monophosphate; Uracil Nucleotides; Pyrimidine Nucleotides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleotides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleotides

Study Officials

• Markus Cornberg, Prof. Dr.

  Hannover Medical School, Clinic for Gastroenterology, Hepatology, and Endocrinology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Prospective, open-label, single-arm multicenter, phase II pilot trial

Study Record Dates

• First Submitted: September 12, 2017
• First Posted: September 14, 2017
• Study Start: December 7, 2017
• Primary Completion: November 26, 2018
• Study Completion: February 18, 2019
• Last Updated: March 8, 2019

Record last verified: 2019-03

Data Sharing

• IPD Sharing: Will not share

Locations

DE (3)