JNJ-73763989 and bersacapavir treatment in nucleos(t)ide analog suppressed patients with chronic hepatitis B : REEF-2
Copyright © 2024. Published by Elsevier B.V..
BACKGROUND & AIMS: Functional cure (FC) for chronic hepatitis B (CHB) requires finite treatment. Two agents under investigation aimed at achieving FC are small interfering RNA JNJ-73763989 (JNJ-3989) and capsid assembly modulator JNJ-56136379 (JNJ-6379; bersacapavir).
METHODS: REEF-2, a phase 2b, double-blind, placebo-controlled, randomized study (ClinicalTrials.gov Identifier: NCT04129554), enrolled 130 nucleos(t)ide analog (NA)-suppressed hepatitis B e-antigen (HBeAg)-negative CHB patients who received JNJ-3989 (200 mg subcutaneously every 4 weeks)+JNJ-6379 (250 mg oral daily)+NA (oral daily; active arm) or placebos for JNJ-3989 and JNJ-6379 + active NA (control arm) for 48 weeks followed by 48 weeks off-treatment follow-up.
RESULTS: At Follow-up Week 24, no patients achieved the primary endpoint of FC (off-treatment hepatitis B surface antigen [HBsAg] seroclearance). No patients achieved FC at Follow-up Week 48. There was pronounced on-treatment reduction in mean HBsAg from baseline at Week 48 in the active arm versus no decline in the control arm (1.89 vs 0.06 log10 IU/mL; P = 0.001). At Follow-up Week 48, reductions from baseline were >1 log10 IU/mL in 81.5% versus 12.5% of patients in the active and control arms, respectively, and 38/81 (46.9%) patients in the active arm achieved HBsAg <100 IU/mL versus 6/40 (15.0%) patients in the control arm. Off-treatment HBV DNA relapse and alanine aminotransferase (ALT) increases were less frequent in the active arm with 7/77 (9.1%) and 11/41 (26.8%) patients in the active and control arms, respectively, restarting NA during follow-up.
CONCLUSIONS: Finite 48-week treatment with JNJ-3989+JNJ-6379+NA resulted in fewer and less severe posttreatment HBV DNA increases and ALT flares, and a higher proportion of patients with off-treatment HBV DNA suppression, with or without HBsAg suppression, but did not result in FC.
CLINICALTRIALS:.
GOV IDENTIFIER: NCT04129554.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2024 |
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| Enthalten in: |
Journal of hepatology - (2024) vom: 05. Apr. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Agarwal, Kosh [VerfasserIn] |
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| Links: |
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| Themen: |
Bersacapavir |
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| Anmerkungen: |
Date Revised 07.04.2024 published: Print-Electronic ClinicalTrials.gov: NCT04129554 Citation Status Publisher |
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| doi: |
10.1016/j.jhep.2024.03.046 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM370729005 |
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| 245 | 1 | 0 | |a JNJ-73763989 and bersacapavir treatment in nucleos(t)ide analog suppressed patients with chronic hepatitis B |b REEF-2 |
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| 500 | |a ClinicalTrials.gov: NCT04129554 | ||
| 500 | |a Citation Status Publisher | ||
| 520 | |a Copyright © 2024. Published by Elsevier B.V. | ||
| 520 | |a BACKGROUND & AIMS: Functional cure (FC) for chronic hepatitis B (CHB) requires finite treatment. Two agents under investigation aimed at achieving FC are small interfering RNA JNJ-73763989 (JNJ-3989) and capsid assembly modulator JNJ-56136379 (JNJ-6379; bersacapavir) | ||
| 520 | |a METHODS: REEF-2, a phase 2b, double-blind, placebo-controlled, randomized study (ClinicalTrials.gov Identifier: NCT04129554), enrolled 130 nucleos(t)ide analog (NA)-suppressed hepatitis B e-antigen (HBeAg)-negative CHB patients who received JNJ-3989 (200 mg subcutaneously every 4 weeks)+JNJ-6379 (250 mg oral daily)+NA (oral daily; active arm) or placebos for JNJ-3989 and JNJ-6379 + active NA (control arm) for 48 weeks followed by 48 weeks off-treatment follow-up | ||
| 520 | |a RESULTS: At Follow-up Week 24, no patients achieved the primary endpoint of FC (off-treatment hepatitis B surface antigen [HBsAg] seroclearance). No patients achieved FC at Follow-up Week 48. There was pronounced on-treatment reduction in mean HBsAg from baseline at Week 48 in the active arm versus no decline in the control arm (1.89 vs 0.06 log10 IU/mL; P = 0.001). At Follow-up Week 48, reductions from baseline were >1 log10 IU/mL in 81.5% versus 12.5% of patients in the active and control arms, respectively, and 38/81 (46.9%) patients in the active arm achieved HBsAg <100 IU/mL versus 6/40 (15.0%) patients in the control arm. Off-treatment HBV DNA relapse and alanine aminotransferase (ALT) increases were less frequent in the active arm with 7/77 (9.1%) and 11/41 (26.8%) patients in the active and control arms, respectively, restarting NA during follow-up | ||
| 520 | |a CONCLUSIONS: Finite 48-week treatment with JNJ-3989+JNJ-6379+NA resulted in fewer and less severe posttreatment HBV DNA increases and ALT flares, and a higher proportion of patients with off-treatment HBV DNA suppression, with or without HBsAg suppression, but did not result in FC | ||
| 520 | |a CLINICALTRIALS: | ||
| 520 | |a GOV IDENTIFIER: NCT04129554 | ||
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| 650 | 4 | |a finite therapy | |
| 650 | 4 | |a hepatitis B virus | |
| 650 | 4 | |a siRNA | |
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| 700 | 1 | |a van Bömmel, Florian |e verfasserin |4 aut | |
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| 700 | 1 | |a Janczewska, Ewa |e verfasserin |4 aut | |
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| 700 | 1 | |a Vanwolleghem, Thomas |e verfasserin |4 aut | |
| 700 | 1 | |a Lenz, Oliver |e verfasserin |4 aut | |
| 700 | 1 | |a Verbinnen, Thierry |e verfasserin |4 aut | |
| 700 | 1 | |a Kakuda, Thomas N |e verfasserin |4 aut | |
| 700 | 1 | |a Mayer, Cristiana |e verfasserin |4 aut | |
| 700 | 1 | |a Jezorwski, John |e verfasserin |4 aut | |
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| 700 | 1 | |a Lonjon-Domanec, Isabelle |e verfasserin |4 aut | |
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