%0 Clinical Trial, Phase I
%T JNJ-56136379, an HBV Capsid Assembly Modulator, Is Well-Tolerated and Has Antiviral Activity in a Phase 1 Study of Patients With Chronic Infection.
%A Zoulim F
%A Lenz O
%A Vandenbossche JJ
%A Talloen W
%A Verbinnen T
%A Moscalu I
%A Streinu-Cercel A
%A Bourgeois S
%A Buti M
%A Crespo J
%A Manuel Pascasio J
%A Sarrazin C
%A Vanwolleghem T
%A Shukla U
%A Fry J
%A Yogaratnam JZ
%J Gastroenterology
%V 159
%N 2
%D 08 2020
%M 32343960
%F 33.883
%R 10.1053/j.gastro.2020.04.036
%X JNJ-56136379 (JNJ-6379), a capsid assembly modulator that blocks hepatitis B virus (HBV) replication, was well tolerated and demonstrated dose-proportional pharmacokinetics in healthy participants in part 1 of its first clinical trial. In part 2, we have evaluated the safety, pharmacokinetics, and antiviral activity of multiple doses of JNJ-6379 in patients with chronic HBV infection.<BR>We performed a double-blind study of 57 treatment-naïve patients with HB e antigen-positive or -negative (74%) chronic HBV infection without cirrhosis. Patients were randomly assigned to groups given JNJ-6379 at 25 mg (100 mg loading dose), 75 mg, 150 mg, or 250 mg or placebo daily for 4 weeks with an 8-week follow-up period.<BR>Twenty-three (56%) of 41 patients given JNJ-6379 had at least 1 adverse event (AE) during treatment, compared with 10 (63%) of 16 patients given placebo. No serious AEs were reported during the treatment period. Three patients (7%) given JNJ-6379 vs none given placebo had grade 3 AEs; of these, 1 patient (150 mg) also had an isolated grade 4 increase in the level of alanine aminotransferase that led to treatment discontinuation. JNJ-6379 exposure increased with dose, with time-linear pharmacokinetics. HBV-DNA and HBV-RNA decreased from baseline in patients receiving all doses of JNJ-6379, independently of viral genotype and HB e antigen status. On day 29, 13 (32%) of 41 patients had levels of HBV DNA below the lower limit of quantification. No clinically significant changes in levels of HB surface antigen were observed.<BR>In a phase 1 study of treatment-naïve patients with chronic HBV infection, all doses tested of JNJ-6379 were well tolerated, showed dose-dependent pharmacokinetics, and had potent antiviral activity in patients with CHB. The findings support a phase 2a study to evaluate JNJ-6379 ± nucleos(t)ide analogs in patients with chronic HBV infection, which is under way. ClinicalTrials.gov identifier: NCT02662712.