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Abstract Details
Safety, antiviral activity and pharmacokinetics of JNJ-64530440, a novel capsid assembly modulator, as 4 week monotherapy in treatment-naive patients with chronic hepatitis B virus infection
J Antimicrob Chemother. 2022 Mar 31;77(4):1102-1110.doi: 10.1093/jac/dkab491.
1New Zealand Liver Transplant Unit, University of Auckland, Auckland, New Zealand.
2Auckland Clinical Studies, Auckland, New Zealand.
3ARENSIA Exploratory Medicine, Republican Clinical Hospital, Chisinau, Moldova.
4State University of Medicine and Pharmacy N. Testemitanu, Chisinau, Moldova.
5Center of Excellence in Hepatitis and Liver Cancer, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
6Janssen Pharmaceutica, NV, Beerse, Belgium.
7Janssen BioPharma Inc., South San Francisco, CA, USA.
8Janssen Pharmaceuticals, Titusville, NJ, USA.
Abstract
Objectives: We investigated JNJ-64530440 (a hepatitis B virus capsid assembly modulator) safety, antiviral activity and pharmacokinetics in patients with chronic hepatitis B (CHB) (Phase 1b, NCT03439488).
Methods: Twenty treatment-naive, HBeAg-positive or -negative CHB patients were randomized 4:1 to JNJ-64530440 750 mg once or twice daily, or placebo for 28 days.
Results: All patients (mean age 43.8 years; 85% male; 70% White; 20% HBeAg positive) completed dosing/28 day follow-up. Mild-to-moderate treatment-emergent adverse events occurred in 3/4 (placebo), 6/8 (once-daily) and 4/8 (twice-daily) patients; mostly fatigue, increased alanine aminotransferase, decreased neutrophil count, and headache. Hepatitis B virus (HBV) DNA was substantially reduced; mean (range) changes from baseline at day 29 were: -3.2 (-2.4 to -3.9) (once-daily) and -3.3 (-2.6 to -4.1) (twice-daily) log10 IU/mL; placebo 0.1 (0.7 to -0.6) log10 IU/mL. HBV DNA levels were below the lower limit of quantification (LLOQ) in 5/8 (once-daily) and 3/8 (twice-daily) patients. For patients with detectable baseline HBV RNA, mean (SE) changes versus baseline in HBV RNA at day 29 were: -2.65 (0.81) (once-daily) and -2.94 (0.33) (twice-daily) log10 copies/mL. HBV RNA levels were 'target not detected' in 4/6 (once-daily) and 3/7 (twice-daily) patients. JNJ-64530440 pharmacokinetics in CHB patients were comparable with those in healthy volunteers.
Conclusions: JNJ-64530440 750 mg once-daily or twice-daily for 28 days was well tolerated and achieved potent antiviral activity in CHB patients.