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Peginterferon alpha-2a add-on to siRNA JNJ-73763989 in untreated patients with HBeAg-positive chronic hepatitis B
Patrick T F Kennedy1, Scott Fung2, Maria Buti3
1Centre for Immunobiology and Infection, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London Faculty of Medicine and Dentistry, London, UK p.kennedy@qmul.ac.uk.
Background:
In the hepatitis B e antigen positive (HBeAg+) chronic infection disease phase, approved treatments have limited effects on hepatitis B surface antigen (HBsAg) and HBeAg.
Objective:
The phase 2 REEF-IT study (NCT04439539) assessed safety, efficacy and pharmacokinetics of pegylated interferon-α2a (PegIFN-α2a) add-on to JNJ-73763989 (JNJ-3989)±bersacapavir+nucleos(t)ide analogues (NA) in not currently treated, HBeAg+chronic hepatitis B.
Design:
Participants received JNJ-3989 (200 mg every 4 weeks)+NA±bersacapavir (250 mg daily) for 36-52 weeks (induction) followed by 12 weeks of PegIFN-α2a (180 µg weekly) add-on. The primary endpoint was the proportion of participants with HBsAg seroclearance 24 weeks after stopping all treatment including NA. Changes in viral markers, safety and pharmacokinetics were assessed.
Results:
49/54 (91%) enrolled participants completed the study; 52% were male, with mean age of 33.6 years. No participant achieved the primary endpoint; one met NA completion criteria. 11/54 (20.4%) participants achieved HBsAg seroclearance at least once, 6 of them maintained it until Follow-up Week 48 (FUW48). Overall mean (SE) change from baseline in HBsAg of -2.85 (0.13), -3.61 (0.18) and -2.63 (0.26)log10IU/mL were observed at end of induction, end of treatment and FUW48. 16/53 (30.2%) participants reached HBeAg seroclearance at least once; 12 maintained it until FUW48. Similar proportions of participants experienced an adverse event (AE) during induction (83.3%), PegIFN-α2a add-on (85.7%) and follow-up (64.7%). There were no deaths or serious AEs; two participants discontinued PegIFN-α2a.
Conclusions:
In this population, adding PegIFN-α2a increased HBsAg declines after reductions by JNJ-3989; 20.4% achieved HBsAg seroclearance at least once. Treatment was generally safe with acceptable tolerability.
Trial Registration Number:
NCT04439539.
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