TY - JOUR
TI - Guidance for design and endpoints of clinical trials in chronic
hepatitis B - Report from the 2019 EASL-AASLD HBV Treatment Endpoints
Conferences
AU - Cornberg, Markus
AU - Lok, Anna Suk-Fong
AU - Terrault, Norah A. and
AU - Zoulim, Fabien
AU - Berg, Thomas
AU - Brunetto, Maurizia R.
AU - Buchholz,
AU - Stephanie
AU - Buti, Maria
AU - Chan, Henry L. Y.
AU - Chang, Kyong-Mi and
AU - Dandri, Maura
AU - Dusheiko, Geoffrey
AU - Feld, Jordan J.
AU - Ferrari,
AU - Carlo
AU - Ghany, Marc
AU - Janssen, Harry L. A.
AU - Kennedy, Patrick and
AU - Lampertico, Pietro
AU - Liang, Jake
AU - Locarnini, Stephen
AU - Maini,
AU - Mala K.
AU - Mishra, Poonam
AU - Papatheodoridis, George
AU - Petersen,
AU - Joerg
AU - Schlottmann, Silke
AU - Wang, Su
AU - Wedemeyer, Heiner
AU - EASL
AU - AASLD HBV Treatment
JO - WORLD JOURNAL OF HEPATOLOGY
PY - 2020
VL - 72
TODO - 3
SP - 539-557
PB - Elsevier
SN - null
TODO - 10.1016/j.jhep.2019.11.003
TODO - Hepatitis D; Hepatitis B surface antigen; Antiviral therapy;
Immunomodulatory therapy; Nucleos(t)ide analogues; CpAM
TODO - Representatives from academia, industry, regulatory agencies, and
patient groups convened in March 2019 with the primary goal of
developing agreement on chronic 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
sterilising 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 III 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 for the
prediction of 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 or negative chronic hepatitis, who
are treatment-naive or virally suppressed on nucleos(t)ide analogues. A
hepatitis flare associated with an increase in bilirubin or
international normalised ratio should prompt temporary or permanent
cessation of an investigational treatment. New treatments must be as
safe as existing nucleos(t)ide analogues. The primary endpoint for phase
III trials for HDV coinfection should be undetectable serum HDV RNA 6
months after stopping treatment. On treatment HDV RNA suppression
associated with normalisation of alanine aminotransferase is considered
an intermediate goal. In conclusion, regarding HBV ‘functional cure’,
the primary goal is sustained HBsAg loss with undetectable HBV DNA after
completion of treatment and the intermediate goal is sustained
undetectable HBV DNA without HBsAg loss after stopping treatment. (C)
2019 European Association for the Study of the Liver and American
Association for the Study of Liver Diseases. Published by Elsevier B.V.
All rights reserved.
ER -