{
  "abstract": "Introduction The dysregulation of both reduced (IL-33 red) and oxidised (IL-33ox) interleukin (IL)-33 has been implicated in chronic obstructive pulmonary disease (COPD) inflammation and remodelling processes. Tozorakimab, an anti-IL-33 monoclonal antibody, inhibits both IL-33red and IL-33ox activity.Methods and analysis The tozorakimab LUNA programme comprises four ongoing, multicentre, randomised, double-blind, parallel-group, placebo-controlled, phase III studies evaluating the efficacy and safety of tozorakimab in participants with symptomatic COPD and a history of exacerbations receiving optimised inhaled therapy. In OBERON ( NCT05166889) and TITANIA (NCT05158387), 1132 and 1172 participants, respectively, were randomised to receive tozorakimab 300 mg every 4 or 8 weeks or placebo for 52 weeks. In MIRANDA (NCT06040086), 1454 participants were randomised 3:2 to tozorakimab 300 mg every 2 weeks or placebo for ≥52 weeks. In PROSPERO (NCT05742802), participants who completed treatment with tozorakimab in OBERON or TITANIA will continue treatment for an additional 28 weeks or 52 weeks; participants recruited from the placebo arm will be re-randomised 1:1 to tozorakimab or placebo. The primary endpoint in OBERON, TITANIA and MIRANDA is the annualised rate of moderate-to-severe COPD exacerbations; the primary endpoint in PROSPERO is the annualised rate of severe COPD exacerbations. For all studies, the primary endpoint will be first assessed in former smokers, then in current and former smokers. Secondary key endpoints include measures of lung function, respiratory symptoms, health status and safety. The tozorakimab LUNA programme is assessing the efficacy and safety of tozorakimab in participants with COPD. It is the largest pivotal programme of any biologic therapy in COPD to date.Ethics and dissemination The protocols were approved by independent ethics committees and institutional review boards. Results of the studies will be submitted to the EU Clinical Trials Information System within a year from the global end of trial data in all participating countries and will be published or presented at scientific meetings.Trial registration number OBERON: NCT05166889; TITANIA: NCT05158387; MIRANDA: NCT06040086; PROSPERO: NCT05742802.",
  "authors": [
    {
      "affiliations": [
        "Velocity Clinical Research Germany, Ahrensburg, Germany",
        "Department of Pulmonary Medicine, University Hospital Schleswig-Holstein, Campus Lübeck, Lübeck, Airway Research Center North (ARCN), German Center for Lung Research (DZL), Großhansdorf, SH, Germany"
      ],
      "name": "Henrik Watz"
    },
    {
      "affiliations": [
        "Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA"
      ],
      "name": "Frank C Sciurba"
    },
    {
      "affiliations": [
        "Department of Public Health and Infectious Diseases, Sapienza University of Rome, Roma, Italy",
        "National Heart and Lung Institute, Imperial College London, London, UK"
      ],
      "name": "Matteo Bonini"
    },
    {
      "affiliations": [
        "Department of Clinical Research, Allergy and Respiratory Disease, InAER, Buenos Aires, Argentina"
      ],
      "name": "Anahi Yañez"
    },
    {
      "affiliations": [
        "PhyMedExp, University of Montpellier, CNRS, INSERM, CHU de Montpellier, Montpellier, France"
      ],
      "name": "Arnaud Bourdin"
    },
    {
      "affiliations": [
        "Guangzhou Institute of Respiratory Health, Guangzhou Medical College First Affiliated Hospital, Guangzhou, China"
      ],
      "name": "Jinping Zheng"
    },
    {
      "affiliations": [
        "Respiratory Department, Population and Health Science Institute, Newcastle University, Newcastle upon Tyne, UK",
        "Freeman Hospital, Sir William Leech Research Centre, Newcastle upon Tyne, UK"
      ],
      "name": "Anthony De Soyza"
    },
    {
      "affiliations": [
        "Respiratory Diseases, University Hospital Leuven & KU Leuven, Leuven, Belgium"
      ],
      "name": "Wim Janssens"
    },
    {
      "affiliations": [
        "University Medical Center Groningen, University of Groningen, Groningen, The Netherlands"
      ],
      "name": "Maarten van den Berge"
    },
    {
      "affiliations": [
        "Department of Respiratory and Critical Care Medicine, Tongji Hospital, Institute of Respiratory Medicine, School of Medicine, Tongji University, Shanghai, China",
        "Department of Respiratory and Critical Care Medicine, Huadong Hospital, Fudan University, Shanghai, China"
      ],
      "name": "Jin-Fu Xu"
    },
    {
      "affiliations": [
        "Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, Maryland, USA"
      ],
      "name": "Gabriela Luporini Saraiva"
    },
    {
      "affiliations": [
        "Biometrics, Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK"
      ],
      "name": "Martin Jenkins"
    },
    {
      "affiliations": [
        "Clinical Pharmacology and Quantitative Pharmacology, Clinical Pharmacology and Safety Sciences, R&D, AstraZeneca, Barcelona, Spain"
      ],
      "name": "Eulalia Jimenez"
    },
    {
      "affiliations": [
        "Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden"
      ],
      "name": "Magnus Lofdahl"
    },
    {
      "affiliations": [
        "Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, Maryland, USA"
      ],
      "name": "Jia Li"
    },
    {
      "affiliations": [
        "Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca, Warsaw, Poland"
      ],
      "name": "Marta Mikosz"
    },
    {
      "affiliations": [
        "Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden"
      ],
      "name": "Natsuko Kishishita"
    },
    {
      "affiliations": [
        "Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden"
      ],
      "name": "Sonya Jackson"
    },
    {
      "affiliations": [
        "Global Medical, Respiratory and Immunology BioPharmaceuticals Medical, AstraZeneca, Cambridge, UK"
      ],
      "name": "Susan Johnson"
    },
    {
      "affiliations": [
        "Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK"
      ],
      "name": "Rajesh Patel"
    },
    {
      "affiliations": [
        "Global Medical, Respiratory and Immunology, BioPharmaceuticals Medical, AstraZeneca, Gothenburg, Sweden"
      ],
      "name": "Malin Fagerås"
    },
    {
      "affiliations": [
        "Clinical Development, Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca, Boston, Massachusetts, USA"
      ],
      "name": "Ioannis Psallidas"
    }
  ],
  "title": "Phase III LUNA clinical programme: design of four randomised, double-blind, placebo-controlled studies assessing the efficacy and safety of tozorakimab in patients with symptomatic COPD and a high risk of exacerbations",
  "uid": "96c195f1-2976-5084-bfe7-4652f7e4de9a"
}