{
  "abstract": "Introduction Systemic sclerosis (SSc) is a rare autoimmune disease characterized by progressive skin and organ fibrosis, vasculopathy, and immune dysregulation with autoantibody production. While skin thickening is a hallmark, SSc also causes Raynaud’s phenomenon (RP), digital ulcers, interstitial lung disease (ILD), pulmonary arterial hypertension (PAH), and cardiac and gastrointestinal complications, which impair quality of life. Autoantibodies are linked to disease subtype, course, and manifestations, suggesting a pathogenic role. Despite progress in SSc management, the need for disease-modifying therapies remains high. Efgartigimod is an IgG1-derived Fc fragment with enhanced FcRn affinity that blocks FcRn to selectively reduce IgG levels. It shows efficacy in several IgG-driven autoimmune diseases. The eSScape study ( NCT06655155) aims to establish proof-of-concept of efgartigimod PH20 SC in patients with SSc.Material and Methods In this phase 2 multicenter, randomized, double-blinded, placebo-controlled study, 81 adults (age >17 years) with SSc will be randomized 2:1 to receive weekly administrations of efgartigimod or placebo PH20 SC (coformulated with recombinant human hyaluronidase PH20) via prefilled syringe. Participants may be on concurrent medication, as determined by the investigator, and will be stratified by disease duration at baseline (<18 or at least 18 months after the first non-RP manifestation) and anti-RNA polymerase III positivity. In total, up to 50% of participants will have no ILD. The study includes a screening period of up to 4 weeks, 48-week treatment, and 56-day safety follow-up period ( figure 1). Key inclusion criteria were an SSc classification as per 2013 ACR/EULAR criteria, ANA seropositivity, Health Assessment Questionnaire-Disability Index (HAQ-DI) score of at least 0.5 or Patient Global Assessment (PGA) score of at least 3, modified Rodnan Skin Score (mRSS) score of at least 15–35, and local mRSS of 1 or less in at least 1 injection site. Exclusion criteria include isolated anticentromere antibody seropositivity, significant PAH, or any condition that would put participants at undue risk.Results The primary endpoint is the change from baseline in mRSS at Week 24. Secondary endpoints include changes from baseline in: mRSS (Week 48); revised Composite Response Index in Systemic Sclerosis (CRISS)-25, HAQ-DI, PGA, and Clinician’s Global Assessment (Weeks 24 and 48); and the annualized rate of Forced Vital Capacity decline in those with ILD. Incidence/severity of treatment-emergent adverse events (AEs), serious AEs, and AEs leading to discontinuation, along with pharmacokinetics, pharmacodynamics, and immunogenicity parameters will also be assessed.Conclusions This phase 2 study will evaluate efgartigimod PH20 SC as a potential treatment for patients with SSc.Abstract P.272 Figure 1Efgartigimod PH20 SC, efgartigimod for SC administration coformulated with rHuPH20; ILD, interstitial lung disease; IMP, investigational medicinal product; rHuPH20, recombinant human hyaluronidase PH20; SC, subcutaneous(ly); SFV, safety follow-up visit",
  "authors": [
    {
      "affiliations": [
        "University of Michigan Scleroderma Program, Ann Arbor, MI, USA"
      ],
      "name": "Dinesh Khanna"
    },
    {
      "affiliations": [
        "University of Leeds, Leeds, UK",
        "Leeds Teaching Hospitals NHS Trust, Leeds, UK"
      ],
      "name": "Francesco Del Galdo"
    },
    {
      "affiliations": [
        "University College London, London, UK"
      ],
      "name": "Christopher P Denton"
    },
    {
      "affiliations": [
        "University of Zurich, Zurich, Switzerland"
      ],
      "name": "Oliver Distler"
    },
    {
      "affiliations": [
        "Nippon Medical School Graduate School of Medicine, Tokyo, Japan"
      ],
      "name": "Masataka Kuwana"
    },
    {
      "affiliations": [
        "argenx, Ghent, Belgium"
      ],
      "name": "Despoina Papadopoulou"
    },
    {
      "affiliations": [
        "argenx, Ghent, Belgium"
      ],
      "name": "Bas Van Der Woning"
    },
    {
      "affiliations": [
        "argenx, Ghent, Belgium"
      ],
      "name": "Erica Falkenbach"
    },
    {
      "affiliations": [
        "argenx, Ghent, Belgium"
      ],
      "name": "Agna Neto"
    },
    {
      "affiliations": [
        "argenx, Ghent, Belgium"
      ],
      "name": "Piotr Zabrocki"
    },
    {
      "affiliations": [
        "IRCCS San Raffaele Hospital, Milan, Italy",
        "Vita Salute San Raffaele University, Milan, Italy"
      ],
      "name": "Marco Matucci-Cerinic"
    }
  ],
  "title": "P.272 Efgartigimod PH20 subcutaneous in adults with systemic sclerosis: a phase 2, randomized, double-blinded, placebo-controlled, parallel-group study (eSScape",
  "uid": "005a7235-d29b-5268-b3f6-e50aac36fcfe"
}