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Challenges, Considerations, and Principles to Guide Trials of Combination Therapies for Chronic Hepatitis B Virus
Ryan Taylor Anderson
University of California, Berkeley, Washington, DC
Seng Gee Lim
National University of Singapore, Singapore, Republic of Singapore
Poonam Mishra
US Food and Drug Administration, Silver Spring, Maryland
Filip Josephson
Swedish Medical Products Agency, Uppsala, Sweden
Eric Donaldson
US Food and Drug Administration, Silver Spring, Maryland
Bruce Given
Arrowhead Pharmaceuticals, Inc., Pasadena, California
Veronica Miller
University of California, Berkeley, Washington, DC
PlumX Metrics
DOI: https://doi.org/10.1053/j.gastro.2018.11.062
Currently approved clinical interventions for chronic hepatitis B (CHB) are limited to treatments that require long-term therapy for the majority of patients. Although observational studies have shown that sustained HBV DNA suppression achieved with current therapies is associated with improvement in clinical outcomes, an excess risk of hepatocellular carcinoma (HCC) remains,1 and hepatitis B surface antigen (HBsAg) seroclearance is uncommon.2 Furthermore, evidence exists that HBsAg seroclearance is associated with decreases in long-term disease complications.3 There is also a need for effective and safe finite therapies to avoid life-long medication.
Renewed interest in the advancement of novel drugs for the treatment of hepatitis B virus (HBV) infection has led to the ongoing development of a broad diversity of agents targeting both the virus and host. The overarching goal of such development is achieving high rates of functional cure, defined as sustained undetectable HBsAg concurrent with suppressed plasma HBV DNA. The Treatment Combinations Working Group of the HBV Forum, a project of the Forum for Collaborative Research, is tasked with developing a conceptual framework for clinical trials that provides adequate safeguards for trial participants while allowing rapid testing and innovation of new treatment combinations aiming at functional cure. In this article, the principles of combination drug development for both trials with ≥2 investigational drugs as well as novel therapeutics combined with already approved treatment options are considered. |
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发表于 2019-2-7 12:53