Cornberg, M;
Lok, AS-F;
Terrault, NA;
Zoulim, F;
2019 EASL-AASLD HBV Treatment Endpoints Conference Faculty;
(2020)
Guidance for design and endpoints of clinical trials in chronic hepatitis B - Report from the 2019 EASL-AASLD HBV Treatment Endpoints Conference.
Hepatology
, 71
(3)
pp. 1070-1092.
10.1002/hep.31030.
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Abstract
Representatives from academia, industry, regulatory agencies, and patient groups convened in March 2019 with the primary goal of developing agreement on chronic hepatitis B virus (HBV) treatment endpoints to guide clinical trials aiming to 'cure' HBV. Agreement among the conference participants was reached on some key points. 'Functional' but not sterilizing cure is achievable and should be defined as sustained HBsAg loss in addition to undetectable HBV DNA 6 months post-treatment. The primary endpoint of phase 3 trials should be functional cure; HBsAg loss in ≥30% of patients was suggested as an acceptable rate of response in these trials. Sustained virologic suppression (undetectable serum HBV DNA) without HBsAg loss, 6 months after discontinuation of treatment would be an intermediate goal. Demonstrated validity in predicting sustained HBsAg loss was considered the most appropriate criterion for the approval of new HBV assays to determine efficacy endpoints. Clinical trials aimed at HBV functional cure should initially focus on patients with HBeAg-positive and HBeAg-negative chronic hepatitis, treatment-naïve or virally suppressed on nucleos(t)ide analogues. A hepatitis flare associated with increase in bilirubin or INR should prompt temporary or permanent cessation of investigational treatment. New treatments must be as safe as existing nucleos(t)ide analogues. The primary endpoint for phase 3 trials for hepatitis D virus (HDV) co-infection should be undetectable serum HDV RNA 6 months after stopping treatment. On treatment HDV RNA suppression associated with normalization of ALT is considered an intermediate goal. CONCLUSION: For HBV 'functional cure', sustained HBsAg loss with undetectable HBV DNA after completion of treatment is the primary goal and sustained undetectable HBV DNA without HBsAg loss after stopping treatment an intermediate goal.
| Type: | Article |
|---|---|
| Title: | Guidance for design and endpoints of clinical trials in chronic hepatitis B - Report from the 2019 EASL-AASLD HBV Treatment Endpoints Conference. |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1002/hep.31030 |
| Publisher version: | https://doi.org/10.1002/hep.31030 |
| Language: | English |
| Additional information: | © 2020 by the American Association for the Study of Liver Diseases and the European Association for the Study of the Liver. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10095195 |
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