{
  "abstract": "Introduction Bronchopulmonary dysplasia (BPD) is the most common complication of prematurity, characterised by impaired alveolarisation and pulmonary vascular development. BPD has been associated with an increased risk of respiratory morbidity, neurodevelopmental impairment and death, intensifying a lifelong health and economic burden. The current standard of neonatal care is primarily supportive, with no approved therapies to restore lung development, promote maturation and lung growth or prevent long-term sequelae. Therefore, there is a critical unmet need for novel interventions, particularly in high-risk, extremely premature (EP) infants. In EP infants, serum insulin-like growth factor-1 (IGF-1) levels decrease rapidly and remain low for the first weeks after birth relative to the corresponding foetal levels in utero.Methods and analysis OHB-607, a recombinant human IGF-1 combined with its binding protein-3, may replenish IGF-1 during this period of deficiency and support lung and vascular maturation. OHB-607 is being investigated as a first-line therapy to prevent severe BPD in EP infants in a Phase 2b, multicentre, open-label, randomised trial. Here, we present the Phase 2b study protocol. Target enrolment is 338 EP infants. To mimic physiological IGF-1 levels in utero, OHB-607 will be administered starting within 24 hours of birth until 29 +6 weeks postmenstrual age (PMA) via continuous intravenous infusion. The primary endpoint is the incidence of severe BPD, based on the modified National Institute of Child Health and Human Development criteria, or death by 36 weeks PMA. Key secondary endpoints include weaning from respiratory support at 12 months corrected age and BPD severity (Grade 2/3) by the 2019 Neonatal Research Network definition. Other secondary endpoints include other complications of prematurity, neurodevelopmental outcomes and family and infant well-being and social functioning through 24 months’ corrected age, and pharmacokinetic and dynamic impact of OHB-607 on the multisystem consequences of prematurity, and overall safety in modifying the natural history of BPD and its consequences.Ethics and dissemination Findings will be disseminated via local and international congresses and publications.Trial registration number ClinicalTrials.gov ( NCT03253263), Clinicaltrialsregister.eu (EudraCT: 2018-001393-16), Euclinicaltrials.eu (EUCT: 2024-515914-41-00) and Pmda.go.jp (PMDA: jRCT2031240339).",
  "authors": [
    {
      "affiliations": [
        "Department of Women's and Children’s Health, University Hospital of Padova, Padova, Italy",
        "‘Città della Speranza’, Institute of Pediatric Research, Padova, Italy"
      ],
      "name": "Eugenio Baraldi"
    },
    {
      "affiliations": [
        "Division of Pediatrics and Neonatal Critical Care, ‘A. Béclère’ Medical Center, Paris Saclay University Hospital, APHP – Paris, Paris, France",
        "Physiopathology and Therapeutic Innovation Unit, Paris Saclay University, Paris, France"
      ],
      "name": "Daniele De Luca"
    },
    {
      "affiliations": [
        "Department of Women's and Children’s Health, University Hospital of Padova, Padova, Italy",
        "‘Città della Speranza’, Institute of Pediatric Research, Padova, Italy"
      ],
      "name": "Luca Bonadies"
    },
    {
      "affiliations": [
        "Department of Neonatal Medicine, Osaka Women's and Children’s Hospital, Osaka, Japan"
      ],
      "name": "Shinya Hirano"
    },
    {
      "affiliations": [
        "Department of Pediatrics, Kyorin University, Tokyo, Japan"
      ],
      "name": "Satoshi Kusuda"
    },
    {
      "affiliations": [
        "Department of Pediatrics, Miller School of Medicine, University of Miami, Miami, Florida, USA"
      ],
      "name": "Eduardo Bancalari"
    },
    {
      "affiliations": [
        "Division of Neonatology, Department of Pediatrics, Cedars-Sinai Guerin Children’s, Cedars-Sinai Medical Center, Los Angeles, California, USA"
      ],
      "name": "Rangasamy Ramanathan"
    },
    {
      "affiliations": [
        "Oak Hill Bio, Altrincham, UK"
      ],
      "name": "Norman Barton"
    },
    {
      "affiliations": [
        "Oak Hill Bio, Altrincham, UK",
        "MMS Holdings, Michigan, Michigan, USA"
      ],
      "name": "Alecia Nickless"
    },
    {
      "affiliations": [
        "Oak Hill Bio, Altrincham, UK"
      ],
      "name": "Jane Lee"
    },
    {
      "affiliations": [
        "Oak Hill Bio, Altrincham, UK"
      ],
      "name": "Navdeep Mahajan"
    },
    {
      "affiliations": [
        "Oak Hill Bio, Altrincham, UK"
      ],
      "name": "Victoria Niklas"
    }
  ],
  "title": "Randomised al.Phase 2b trial of rhIGF-1/rhIGFBP-3 (OHB-607) for bronchopulmonary dysplasia prevention in preterm neonates: study protocol",
  "uid": "c38764b6-abed-516e-998c-2ebbd8168f7c"
}