Original ResearchFull Report: Clinical—LiverSafety and Efficacy of 48 Weeks REP 2139 or REP 2165, Tenofovir Disoproxil, and Pegylated Interferon Alfa-2a in Patients With Chronic HBV Infection Naïve to Nucleos(t)ide Therapy
Graphical abstract
Section snippets
Study Design
The REP 401 study is an open-label, randomized, controlled, phase 2 study assessing the safety and efficacy of addition of either REP 2139-Mg or REP 2165-Mg (250-mg intravenous infusion every week) to a backbone therapy of TDF (Viread, 300 mg oral every day) and pegIFN (Pegasys, 180 μg subcutaneous every week). Calculation of statistical power in the REP 401 study was based on historical HBsAg response observed in previous trials with NAPs vs HBsAg response observed with pegIFN or pegIFN + NUCs
Participants
Forty noncirrhotic participants with chronic HBeAg-negative HBV infection (HBsAg >1000 IU/mL and HBV DNA >2000 IU/mL) were enrolled between September 2015 and June 2016 with complete results available in April 2019. Group characteristics at baseline and at randomization are shown in Table 1 and disposition of participants from recruitment to the end of follow-up is presented in Supplementary Figure 1.
Adverse Events During the Conduct of the Study
Unrelated serious adverse events (AEs) included 1 case of pneumonia, which resolved within 2
Discussion
Administration tolerability of REP 2139-Mg and REP 2165-Mg in the REP 401 study was improved over REP 2139-Ca from previous studies,9,12 indicating that subcutaneous administration of REP 2139-Mg or REP 2165-Mg will also be well tolerated. Delivery of NAPs to the liver occurs with subcutaneous administration in vivo22 and the safety and efficacy of subcutaneous administration of REP 2139-Mg will be examined in future studies.
All PS-ONs are accompanied by mild but stable depression of platelet
Acknowledgments
The conduct of the study was supported by Replicor Inc. The authors thank Dr Sergiu Merioara for his assistance during the study.
CRediT Authorship Contributions
Michel Bazinet, MD (Conceptualization: Equal; Methodology: Supporting); Victor Pântea, MD (Investigation: Lead; Writing – original draft: Supporting; Writing – review & editing: Supporting); Gheorghe Placinta, MD (Investigation: Lead; Writing – original draft: Supporting; Writing – review & editing: Supporting); Iurie Moscalu, MD (Investigation: Lead; Writing –
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Conflict of interest These authors disclose the following: Michel Bazinet and Andrew Vaillant are employees and shareholders of Replicor Inc. and inventors of patents assigned to Replicor. The Institute for Virology received compensation from Replicor for performing virologic diagnostics. The remaining authors disclose no conflicts.
Funding Supported by Replicor Inc.