{
  "abstract": "Background Preclinical evidence suggests targeting the mid-region of tau as a viable therapeutic strategy in diseases such as progressive supranuclear palsy (PSP): a rare, fatal, neurodegenerative tauopathy with no currently approved treatments. Bepranemab is a recombinant, humanised, full-length immunoglobulin G4 monoclonal antibody binding to a mid-region tau epitope. We assessed safety, tolerability and pharmacokinetics of bepranemab in participants with PSP.Methods PSP003 ( NCT04185415), a multicentre, double-blind, placebo-controlled, phase 1b study, recruited participants in hospital settings across 13 centres. Participants (aged ≥40 years) met Movement Disorder Society-PSP criteria for possible/probable PSP, could walk ≥5 steps with minimal/no assistance and were stable on treatment for ≥2 weeks prior to baseline. Participants were randomised 3:1 to receive intravenous bepranemab (90 mg/kg) or placebo every 4 weeks for 52 weeks. Primary endpoint: incidence of treatment-emergent adverse events (TEAEs) from baseline to last visit.Results Twenty-five participants were enrolled (male: 44%; bepranemab n=18, placebo n=7). Seventeen (94.4%) in the bepranemab group reported ≥1 TEAE (five participants; ten investigational medicinal product (IMP)-related TEAEs), versus placebo (n=7; 100%). In the bepranemab and placebo groups, respectively, three participants (16.7%) and one participant (14.3%) discontinued due to TEAEs. Incidence of IMP-related TEAEs and severe TEAEs was similar between groups; no deaths were reported. Reduction (80.41%) in mean free tau cerebrospinal fluid levels was observed in the bepranemab group.Conclusions Multiple doses of bepranemab 90 mg/kg were well tolerated with an acceptable safety profile in participants with PSP. High target occupancy was observed.",
  "authors": [
    {
      "affiliations": [
        "Department of Neurology, LMU University Hospital, Ludwig-Maximilians-Universität (LMU), Munich, Germany",
        "Munich Cluster for Systems Neurology (SyNergy), Munich, Germany",
        "German Center for Neurodegenerative Diseases e.V. (DZNE), Munich, Germany",
        "Hannover Medical School, Hanover, Germany"
      ],
      "name": "Günter Höglinger"
    },
    {
      "affiliations": [
        "Department of Neurology, UZ Leuven, Leuven, Belgium",
        "Department of Neurosciences, KU Leuven, Leuven, Belgium"
      ],
      "name": "Wim Vandenberghe"
    },
    {
      "affiliations": [
        "Contilia Gruppe, Essen, Germany"
      ],
      "name": "Dirk Woitalla"
    },
    {
      "affiliations": [
        "Sorbonne Université, Paris Brain institute – ICM, Assistance Publique – Hôpitaux de Paris, Inserm, CNRS, Department of Neurology, Pitié-Salpêtrière Hospital, Paris, France"
      ],
      "name": "Jean-Christophe Corvol"
    },
    {
      "affiliations": [
        "UCB, Braine-l’Alleud, Belgium"
      ],
      "name": "Hans Van Tricht"
    },
    {
      "affiliations": [
        "UCB, Slough, UK"
      ],
      "name": "Colin Ewen"
    },
    {
      "affiliations": [
        "UCB, Braine-l’Alleud, Belgium"
      ],
      "name": "Bart Van Den Steen"
    },
    {
      "affiliations": [
        "UCB, Madrid, Spain"
      ],
      "name": "Irene Rebollo Mesa"
    },
    {
      "affiliations": [
        "UCB, Braine-l’Alleud, Belgium"
      ],
      "name": "Massimiliano Germani"
    },
    {
      "affiliations": [
        "UCB, Braine-l’Alleud, Belgium"
      ],
      "name": "Elodie Garric"
    },
    {
      "affiliations": [
        "UCB (contracted via Veramed Ltd, Twickenham, UK), Braine-l’Alleud, Belgium"
      ],
      "name": "Tasmin Arnould"
    },
    {
      "affiliations": [
        "UCB, Slough, UK"
      ],
      "name": "Joby Jose"
    },
    {
      "affiliations": [
        "UCB, Smyrna, Georgia, USA"
      ],
      "name": "Nancy Strong"
    },
    {
      "affiliations": [
        "UCB, Braine-l’Alleud, Belgium"
      ],
      "name": "Steven De Bruyn"
    },
    {
      "affiliations": [
        "UCB, Braine-l’Alleud, Belgium"
      ],
      "name": "Tim J Buchanan"
    }
  ],
  "title": "Safety, tolerability and biomarker results of bepranemab in participants with progressive supranuclear palsy: a randomised, multicentre, double-blind, placebo-controlled, phase 1b trial",
  "uid": "11e6e27c-bb12-5195-980b-96e6984bf51f"
}