{
  "abstract": "Introduction Systemic sclerosis (SSc) is a rare autoimmune disease characterized by inflammation, vascular dysfunction, and fibrosis. Diffuse cutaneous (dc) SSc is associated with more severe outcomes, and treatment options remain limited. Tibulizumab, an investigational dual-antagonist antibody, designed to neutralize interleukin-17A (IL-17A) and B-cell activating factor (BAFF), is being evaluated for its potential to treat SSc, including skin and lung involvement.Material and Methods This randomized, double-blind, placebo-controlled study will evaluate the efficacy, safety, and tolerability of tibulizumab in adults with dcSSc over 24-weeks, followed by a 28-week open-label extension (OLE) ( NCT06843239).Approximately 80 adults aged 18–75 years with dcSSc less than/equal to 7 years duration, with or without interstitial lung disease (SSc-ILD), will be randomized 1:1 to receive tibulizumab or placebo every 4 weeks (Q4W) from Day1 through Week 20, with an additional dose at Week 2. Participants who complete treatment in the double-blind period will be eligible for the OLE, in which all participants will receive tibulizumab Q4W from Week 24 through Week 48, with safety follow-up through Week 60.The primary endpoint is change from baseline (CFB) in modified Rodnan Skin Score (mRSS) at Week 24. Key secondary endpoints will include CFB in lung fibrosis by high-resolution computed tomography (HRCT)), forced vital capacity (FVC, mL), Health Assessment Questionnaire–Disability Index (HAQ-DI), with safety and tolerability assessed through treatment-emergent adverse events (TEAEs), electrocardiograms (ECGs), vital signs, and clinical laboratory assessments.Key inclusion criteria: dcSSc with first non-Raynaud’s Phenomenon sign/symptom less than/equal to 7 years, mRSS 15–45, FVC >50%, DLCO greater than/equal to 40%. Key exclusion criteria: Anti-centromere antibody (ACA)-positive, active organ complications, prior tibulizumab exposure, and recent use of select biologic therapies. Stable use of an oral immunosuppressive and/or antifibrotic therapy is allowed.Results An R-based population-PK model was developed using data from a previous Ph1b study in participants with Sjögren’s syndrome, and 1000 individual patient simulations were conducted for a given dose regimen. The model predicted that at steady state the selected dosing regimen will elicit a >98% median reduction in trough free target (IL-17 and BAFF) in blood. In skin and lung tissue, the median trough reduction in IL-17 and BAFF is predicted to be >80% at steady state. Due to inclusion of the additional dose at week 2, these levels are achieved by week 4.Conclusions TibuSURE is the first study to evaluate dual inhibition of IL-17A and BAFF with tibulizumab in dcSSc, aiming to evaluate skin and lung outcomes.Abstract P.267 Figure 1Study schema",
  "authors": [
    {
      "affiliations": [
        "UCL Division of Medicine",
        "UCL Centre for Rheumatology and Connective Tissue Diseases, Royal Free Hospital, London, UK"
      ],
      "name": "Christopher Denton"
    },
    {
      "affiliations": [
        "Zura Bio, Henderson, USA"
      ],
      "name": "Brandon Walsh"
    },
    {
      "affiliations": [
        "Zura Bio, Henderson, USA"
      ],
      "name": "Vaishali Moulton"
    },
    {
      "affiliations": [
        "Zura Bio, Henderson, USA"
      ],
      "name": "Shelly Shirkey"
    },
    {
      "affiliations": [
        "Zura Bio, Henderson, USA"
      ],
      "name": "Kate Lindsell"
    },
    {
      "affiliations": [
        "Zura Bio, Henderson, USA"
      ],
      "name": "Marjan Sepassi"
    },
    {
      "affiliations": [
        "Zura Bio, Henderson, USA"
      ],
      "name": "Kiran Nistala"
    },
    {
      "affiliations": [
        "Division of Rheumatology, Department of Internal Medicine, University of Michigan, Ann Arbor, USA"
      ],
      "name": "Dinesh Khanna"
    }
  ],
  "title": "P.267 Tibusure: a phase 2, global, randomized, double-blind, placebo-controlled study with open-label extension to evaluate the efficacy, safety, and tolerability of tibulizumab in systemic sclerosis",
  "uid": "412e947e-93aa-5275-ac3b-96bed0dab6d6"
}