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JNJ-56136379, an HBV capsid assembly modulator, is well-tolerated and has antiviral activity in a phase 1 study of patients with chronic infection

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Background & Aims 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. Methods 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. Results Twenty-three of 41 patients (56%) given JNJ-6379 had at least 1 adverse event (AE) during treatment, compared with 10/16 patients (63%) 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 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, 13/41 patients (32%) had levels of HBV DNA below the lower limit of quantification. No clinically significant changes in levels of HB surface antigen were observed. Conclusions 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 underway.
Tijdschrift: Gastroenterology
ISSN: 0016-5085
Volume: 159
Pagina's: 521 - 533
Jaar van publicatie:2020
Trefwoorden:A1 Journal article
BOF-keylabel:ja
Toegankelijkheid:Open