{
  "abstract": "Introduction Systemic sclerosis (SSc) is a rare, autoimmune, inflammatory and multisystem connective tissue disease, characterised by widespread vasculopathy and abnormal collagen deposition, leading to fibrosis of the skin and internal organs with significant morbidity and mortality. Preclinical and clinical evidence supports a pathogenic role for interleukin (IL)-31 signalling in driving fibrosis. Nemolizumab, a humanised monoclonal antibody targeting the IL-31 receptor alpha (IL-31RA) chain, is expected to confer both anti-inflammatory and antifibrotic effects by reducing skin thickening and slowing the progression of pulmonary fibrosis in SSc-associated interstitial lung disease.Methods THESSALIA ( NCT07047690) is a phase II, randomised, double-blind, placebo-controlled, dose-ranging study with an extension phase evaluating the efficacy, safety and pharmacokinetics of nemolizumab in adult patients with limited or diffuse cutaneous SSc with active disease. 162 patients are planned to be recruited. Efficacy will be assessed at week 52 by change from baseline in modified Rodnan skin score (primary endpoint). Lung function and the overall disease activity will be assessed via change from baseline in forced vital capacity (FVC) in patients with SSc-associated interstitial lung disease and the revised Composite Response Index in SSc, respectively (key secondary endpoints). Comprehensive safety, pharmacokinetic, immunogenicity and exploratory biomarker assessments and genotyping are also included.Analysis The THESSALIA study is currently recruiting patients and is planned to be conducted at approximately 120 sites globally.Ethics and dissemination The sponsor has ensured that the local Institutional Review Board/Independent Ethics Committee in all countries involved approved the study.Trial registration number NCT07047690.",
  "authors": [
    {
      "affiliations": [
        "Department of Rheumatology, University Hospital Zurich, Zürich, Switzerland"
      ],
      "name": "Oliver Distler"
    },
    {
      "affiliations": [
        "University of Michigan, Ann Arbor, Michigan, USA"
      ],
      "name": "Dinesh Khanna"
    },
    {
      "affiliations": [
        "Hospital for Special Surgery and Weill Medical College, New York, New York, USA"
      ],
      "name": "Robert Spiera"
    },
    {
      "affiliations": [
        "Division of Rheumatology, University of Michigan, Ann Arbor, Michigan, USA",
        "Department of Dermatology, University of Michigan, Ann Arbor, Michigan, USA"
      ],
      "name": "Johann E Gudjonsson"
    },
    {
      "affiliations": [
        "Galderma SA, Zug, ZG, Switzerland"
      ],
      "name": "Valerie Julia"
    },
    {
      "affiliations": [
        "Galderma R&D, Fort Worth, Texas, USA"
      ],
      "name": "Nathalie Wagner"
    },
    {
      "affiliations": [
        "Galderma SA, Zug, ZG, Switzerland"
      ],
      "name": "Matteo Rossini"
    },
    {
      "affiliations": [
        "Galderma R&D, Boston, Massachusetts, USA"
      ],
      "name": "Julie Zhu"
    },
    {
      "affiliations": [
        "Galderma SA, Zug, ZG, Switzerland"
      ],
      "name": "Christophe Piketty"
    }
  ],
  "title": "Phase II randomised, double-blind, placebo-controlled, dose-ranging study of nemolizumab with an extension period in adult patients with systemic sclerosis: THESSALIA study design and rationale",
  "uid": "fb4dcc0b-43f3-54f9-b704-9addfee2f195"
}