{
  "abstract": "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)log 10IU/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.",
  "authors": [
    {
      "affiliations": [
        "Centre 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"
      ],
      "name": "Patrick T F Kennedy"
    },
    {
      "affiliations": [
        "University of Toronto, Toronto, Ontario, Canada"
      ],
      "name": "Scott Fung"
    },
    {
      "affiliations": [
        "Hepatology, Hospital General Universitari Valle, Pg. de la Vall d’Hebron, Barcelona, Spain"
      ],
      "name": "Maria Buti"
    },
    {
      "affiliations": [
        "Trabzon Karadeniz Technical University Farabi Hospital, Trabzon, Turkey"
      ],
      "name": "Gurdal Yilmaz"
    },
    {
      "affiliations": [
        "Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan"
      ],
      "name": "Wan-Long Chuang"
    },
    {
      "affiliations": [
        "Hepatology, Université de Paris-Cité, INSERM UMR1149, Department of Hepatology, AP-HP Hôpital Beaujon, Clichy, France"
      ],
      "name": "Tarik Asselah"
    },
    {
      "affiliations": [
        "Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan"
      ],
      "name": "Masayuki Kurosaki"
    },
    {
      "affiliations": [
        "Johnson & Johnson, Titusville, New Jersey, USA"
      ],
      "name": "John Jezorwski"
    },
    {
      "affiliations": [
        "Johnson & Johnson, Titusville, New Jersey, USA"
      ],
      "name": "Vladislav Klyashtornyy"
    },
    {
      "affiliations": [
        "Johnson & Johnson, Beerse, Belgium"
      ],
      "name": "Thierry Verbinnen"
    },
    {
      "affiliations": [
        "Johnson & Johnson, San Diego, California, USA"
      ],
      "name": "Thomas Naoki Kakuda"
    },
    {
      "affiliations": [
        "Johnson & Johnson, Beerse, Belgium"
      ],
      "name": "Oliver Lenz"
    },
    {
      "affiliations": [
        "Johnson & Johnson, Beerse, Belgium"
      ],
      "name": "Carine Guinard-Azadian"
    },
    {
      "affiliations": [
        "Johnson & Johnson, Beerse, Belgium"
      ],
      "name": "Michael Biermer"
    }
  ],
  "title": "Peginterferon alpha-2a add-on to siRNA JNJ-73763989 in untreated patients with HBeAg-positive chronic hepatitis B virus (HBV) infection: the phase 2 REEF-IT study",
  "uid": "56a5bd78-cd9c-5143-b6c7-3e8edb99ca60"
}