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.

ABSTRACT

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) log10 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) log10 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) log10 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.