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
© The Author(s) 2022. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:77 |
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| Enthalten in: |
The Journal of antimicrobial chemotherapy - 77(2022), 4 vom: 31. März, Seite 1102-1110 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Gane, Ed J [VerfasserIn] |
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| Links: |
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| Themen: |
Antiviral Agents |
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| Anmerkungen: |
Date Completed 01.04.2022 Date Revised 02.06.2022 published: Print ClinicalTrials.gov: NCT03439488 Citation Status MEDLINE |
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| doi: |
10.1093/jac/dkab491 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM335757073 |
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| 100 | 1 | |a Gane, Ed J |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a 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 |
| 264 | 1 | |c 2022 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 01.04.2022 | ||
| 500 | |a Date Revised 02.06.2022 | ||
| 500 | |a published: Print | ||
| 500 | |a ClinicalTrials.gov: NCT03439488 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © The Author(s) 2022. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. | ||
| 520 | |a 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) | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a CONCLUSIONS: JNJ-64530440 750 mg once-daily or twice-daily for 28 days was well tolerated and achieved potent antiviral activity in CHB patients | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Randomized Controlled Trial | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Antiviral Agents |2 NLM | |
| 650 | 7 | |a DNA, Viral |2 NLM | |
| 650 | 7 | |a Hepatitis B e Antigens |2 NLM | |
| 700 | 1 | |a Schwabe, Christian |e verfasserin |4 aut | |
| 700 | 1 | |a Berliba, Elina |e verfasserin |4 aut | |
| 700 | 1 | |a Tangkijvanich, Pisit |e verfasserin |4 aut | |
| 700 | 1 | |a Jucov, Alina |e verfasserin |4 aut | |
| 700 | 1 | |a Ghicavii, Nelea |e verfasserin |4 aut | |
| 700 | 1 | |a Verbinnen, Thierry |e verfasserin |4 aut | |
| 700 | 1 | |a Lenz, Oliver |e verfasserin |4 aut | |
| 700 | 1 | |a Talloen, Willem |e verfasserin |4 aut | |
| 700 | 1 | |a Kakuda, Thomas N |e verfasserin |4 aut | |
| 700 | 1 | |a Westland, Chris |e verfasserin |4 aut | |
| 700 | 1 | |a Patel, Megha |e verfasserin |4 aut | |
| 700 | 1 | |a Yogaratnam, Jeysen Z |e verfasserin |4 aut | |
| 700 | 1 | |a Dragone, Leonard |e verfasserin |4 aut | |
| 700 | 1 | |a Van Remoortere, Pieter |e verfasserin |4 aut | |
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