| Autor: |
Ed J. Gane, Christian Schwabe, Elina Berliba, Pisit Tangkijvanich, Alina Jucov, Nelea Ghicavii, Thierry Verbinnen, Oliver Lenz, Willem Talloen, Thomas N. Kakuda, Chris Westland, Megha Patel, Jeysen Z. Yogaratnam, Leonard Dragone, Pieter Van Remoortere |
| Rok vydání: |
2021 |
| Předmět: |
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| Zdroj: |
The Journal of antimicrobial chemotherapy. 77(4) |
| ISSN: |
1460-2091 |
| Popis: |
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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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