Liver Safety Assessment in Clinical Trials of New Agents for Chronic Hepatitis B

Robert J. Fontana; Mark I. Avigan; Harry L. A. Janssen; Arie Regev; Poonam Mishra; Anuj Gaggar; Nathaniel Brown; Cynthia Wat; Patricia Mendez; Ryan T. Anderson; Bruce Given; Veronica Miller; Maria Beumont


J Viral Hepat. 2020;27(2):96-109. 

In This Article

Collection of Pretreatment DNA and on Treatment Biobanked Samples

Liver safety issues are a leading reason for drugs to fail in clinical development.[56] With a typically low incidence in drug-exposed patients, genetic variation in host receptors, metabolic pathways and/or immune response may be involved in idiosyncratic DILI pathogenesis.[57] Studies exploring the mechanism and risk factors for drugs that did not gain regulatory approval due to DILI have identified high-risk patients using genomic and immunological methods.[58] Therefore, sponsors are encouraged to collect a predosing DNA sample in all clinical trial participants in the event that untoward adverse events such as DILI are noted during the drug development programme. In addition, blood samples for efficacy and safety markers should be obtained at baseline and at key study visits during and at the end of dosing and follow-up so that future studies of DILI risk vs drug benefit can be undertaken.