Gastroenterology. 2020 Apr 25. pii: S0016-5085(20)30519-9. doi: 10.1053/j.gastro.2020.04.036. [Epub ahead of print]
JNJ-56136379, an HBV Capsid Assembly Modulator, is Well-Tolerated and Has Antiviral Activity in a Phase 1 Study of Patients with Chronic Infection.
Zoulim F1, Lenz O2, Vandenbossche JJ2, Talloen W2, Verbinnen T2, Moscalu I3, Streinu-Cercel A4, Bourgeois S5, Buti M6, Crespo J7, Pascasio JM8, Sarrazin C9, Vanwolleghem T10, Shukla U11, Fry J12, Yogaratnam JZ12.
Author information
1
Hepatology Unit, Hospices Civils de Lyon and Lyon University, Lyon, France & INSERM U1052-Cancer Research Institute of Lyon, Lyon, France. Electronic address: [email protected].
2
Janssen Pharmaceuticals NV, Beerse, Belgium.
3
Spitalul Clinic Republican, ARENSIA EM, Chișinău, Moldova.
4
National Institute for Infectious Diseases "Prof. Dr Matei Bals", Carol Davila University of Medicine and Pharmacy, Bucharest, Romania.
5
ZNA Jan Palfijn, CPU, Antwerp, Belgium.
6
Hospital Universitario Vall d'Hebrón and CIBERHED del Instituto Carlos III, Barcelona, Spain.
7
Hospital Universitario Marqués de Valdecilla, IDIVAL Santander, Spain.
8
Hospital Universitario Virgen del Rocio, Seville, Spain.
9
Medizinische Klinik II, St. Josefs-Hospital, Weisbaden, Germany.
10
Erasmus MC, University Medical Center, Rotterdam, Netherlands; Antwerp University Hospital, Antwerp, Belgium.
11
Janssen Pharmaceuticals R&D, Titusville, New Jersey, USA. Electronic address: [email protected].
12
Janssen Biopharma Inc., South San Francisco, USA.
Abstract
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. ClinicalTrials.gov identifier: NCT02662712.