Safety and efficacy of bulevirtide in combination with tenofovir disoproxil fumarate in patients with hepatitis B virus and hepatitis D virus coinfection (MYR202): a multicentre, randomised, parallel-group, open-label, phase 2 trial

Autor: Heiner Wedemeyer, Katrin Schöneweis, Pavel Bogomolov, Antje Blank, Natalia Voronkova, Tatiana Stepanova, Olga Sagalova, Vladimir Chulanov, Marina Osipenko, Viacheslav Morozov, Natalia Geyvandova, Snezhana Sleptsova, Igor G Bakulin, Ilsiyar Khaertynova, Marina Rusanova, Anita Pathil, Uta Merle, Birgit Bremer, Lena Allweiss, Florian A Lempp, Kerstin Port, Mathias Haag, Matthias Schwab, Julian Schulze zur Wiesch, Markus Cornberg, Walter E Haefeli, Maura Dandri, Alexander Alexandrov, Stephan Urban
Rok vydání: 2021
Předmět:
Zdroj: The Lancet. Infectious diseases. 23(1)
ISSN: 1474-4457
Popis: Bulevirtide is a first-in-class peptidic entry inhibitor for hepatitis B virus (HBV) and hepatitis D virus infection. In July, 2020, bulevirtide 2 mg received conditional marketing authorisation by the European Medical Agency for treatment of chronic hepatitis D virus infection. We investigated the antiviral activity of bulevirtide in patients chronically infected with HBV and hepatitis D virus.MYR202 (ClinicalTrials.gov, NCT03546621; EudraCT, 2016-000395-13) was a multicentre, parallel-group, randomised, open-label, phase 2 trial. Adults (aged 18-65 years) with chronic hepatitis D virus infection, including patients with cirrhosis and patients who had contraindications to PegIFNα treatment or for whom treatment did not work, were eligible and were enrolled from four hospitals in Germany and 12 hospitals in Russia. Patients were randomly assigned (1:1:1:1) to receive 2 mg (n=28), 5 mg (n=32), or 10 mg (n=30) subcutaneous bulevirtide once per day with tenofovir disoproxil fumarate (TDF; 245 mg once per day orally) or TDF alone (245 mg once per day orally; n=30) for 24 weeks. Randomisation was done using a digital block scheme with stratification, consisting of 480 randomisation numbers separated into 30 blocks. The primary endpoint was undetectable hepatitis D virus RNA or 2 logBetween Feb 16, 2016, and Dec 8, 2016, 171 patients with chronic hepatitis D virus infection were screened; 51 were ineligible based on the exclusion criteria and 120 patients (59 with cirrhosis) were enrolled. At week 24, 15 (54%, 95% CI 34-73) of 28 patients achieved undetectable hepatitis D virus RNA or a 2 logBulevirtide induced a significant decline in hepatitis D virus RNA over 24 weeks. After cessation of bulevirtide, hepatitis D virus RNA concentrations rebounded. Longer treatment durations and combination therapies should be investigated.Hepatera LLC, MYR GmbH, and the German Centre for Infection Research, TTU Hepatitis.
Databáze: OpenAIRE