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 (1, 2) , Jinlin Hou (3) , Tarik Asselah (4, 5) , Henry L Y Chan (6) , Fabien Zoulim (7, 8) , Yasuhito Tanaka (9) , Ewa Janczewska (10) , Ronald G Nahass (11) , Stefan Bourgeois (12) , Maria Buti (13) , Pietro Lampertico (14, 15) , Oliver Lenz (16) , Thierry Verbinnen (16) , Joris Vandenbossche (16) , Willem Talloen (16) , Ronald Kalmeijer (17) , Maria Beumont (17) , Michael Biermer (16) , Umesh Shukla (17)

1 TGHRI - Toronto General Hospital Research Institute [Canada]
2 Erasmus MC - Erasmus University Medical Center [Rotterdam]
3 Southern Medical University [Guangzhou]
4 CRI (UMR_S_1149 / ERL_8252 / U1149) - Centre de recherche sur l'Inflammation
5 Hôpital Beaujon [AP-HP]
6 CUHK - The Chinese University of Hong Kong [Hong Kong]
7 UNICANCER/CRCL - Centre de Recherche en Cancérologie de Lyon
8 HCL - Hospices Civils de Lyon
9 Kumamoto University
10 SUM - Medical University of Silesia
11 ID care
12 ZNA - Ziekenhuis Netwerk Antwerpen
13 Vall d'Hebron University Hospital [Barcelona]
14 Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico
15 UNIMI - Università degli Studi di Milano = University of Milan
16 Janssen Pharmaceutica [Beerse]
17 Janssen Research & Development

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) log 10 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) log 10 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) log 10 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.

Mots clés: CHRONIC HEPATITIS; CLINICAL TRIALS; HEPATITIS B

Domaines: Hépatologie et Gastroentérologie

Harry L A Janssen, Jinlin Hou, Tarik Asselah, Henry L Y Chan, Fabien Zoulim, et al.. 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. Gut, 2023, 72, pp.1385 - 1398. ⟨10.1136/gutjnl-2022-328041⟩. ⟨hal-04165783⟩