Randomised phase 2 study (JADE) of the HBV capsid assembly modulator JNJ-56136379 with or without a nucleos(t)ide analogue in patients with chronic hepatitis B infection

Harry L.A. Janssen, Jinlin Hou, Tarik Asselah, Henry L.Y. Chan, Fabien Zoulim, Yasuhito Tanaka, Ewa Janczewska, Ronald G. Nahass, Stefan Bourgeois, Maria Buti, Pietro Lampertico, Oliver Lenz, Thierry Verbinnen, Joris Vandenbossche, Willem Talloen, Ronald Kalmeijer, Maria Beumont, Michael Biermer*, Umesh Shukla

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

Objective: We present the final analysis results of the phase 2 JADE study (ClinicalTrials.gov Identifier: NCT03361956). Design: 232 patients with chronic hepatitis B (CHB) not currently treated at study start (NCT) at study start or virologically suppressed were randomised to receive 75 mg (part 1) or 250 mg (part 2) JNJ-56136379, a hepatitis B virus (HBV)-capsid assembly modulator, one time per day or placebo with nucleos(t)ide analogue (NA) (tenofovir disoproxil fumarate/entecavir) or JNJ-56136379 alone (NCT-only) for ≥24 and ≤48 weeks. Results: In patients who are NCT hepatitis B e-antigen (HBeAg) positive, JNJ-56136379 75 mg+NA and 250 mg+NA showed limited mean (SE) hepatitis B surface antigen (HBsAg) declines (0.14 (0.10) and 0.41 (0.15), respectively) from baseline at Week 24 (primary endpoint; placebo+NA: 0.25 (0.11) log10 international unit (IU)/mL). In patients who are NCT HBeAg positive, mean (SE) HBV DNA declines at Week 24 were 5.53 (0.23) and 5.88 (0.34) for JNJ-56136379 75 mg+NA and 250 mg+NA, respectively, versus 5.21 (0.42) log10 IU/mL for placebo+NA. In NCT patients, mean (SE) HBV RNA declines were 2.96 (0.23) and 3.15 (0.33) versus 1.33 (0.32) log10 copies/mL, respectively. Patients with HBsAg declines had HBeAg and hepatitis B core-related antigen (HBcrAg) declines and some early on-treatment isolated alanine aminotransferase flares. Viral breakthrough occurred with JNJ-56136379 monotherapy with the emerging resistant-variant T33N, but not with JNJ-56136379+NA. JNJ-56136379 treatment beyond Week 24 had a generally small additional effect on viral markers. No study treatment-related serious adverse events or clinically significant changes in laboratory parameters occurred. Conclusions: In patients with non-cirrhotic CHB, JNJ-56136379+NA showed pronounced reductions in HBV DNA and HBV RNA, limited HBsAg or HBeAg declines in patients who are NCT HBeAg positive, and was well tolerated, but no clear benefit with regards to efficacy of JNJ-56136379 over NA was observed.

Original languageEnglish
Article numbergutjnl-2022-328041
Pages (from-to)1385-1398
Number of pages14
JournalGut
Volume72
Issue number7
Early online date25 Jan 2023
DOIs
Publication statusPublished - 1 Jul 2023

Bibliographical note

Funding Information:
This study was sponsored by Janssen (award/grant number: not applicable).

Publisher Copyright:
© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

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