AB0877 TARGETING VASCULOPATHY TO SLOW FIBROSIS IN SYSTEMIC SCLEROSIS (SSC): DESIGN OF A PHASE II STUDY WITH A SOLUBLE GUANYLATE CYCLASE ACTIVATOR (SGCA)

Background The pathophysiology of SSc involves a complex interplay between immune dysfunction, vasculopathy, and fibrosis. soluble guanylate cyclase (sGC) pathway has been shown to improve vascular endothelial function. We designed Phase II study test whether treatment vasculopathy with an sGCa could slow the progression fibrosis in patients early progressive vasculopathy. Objectives To design randomized, double-blind, placebo-controlled trial evaluate treated sGCa. Methods reviewed criteria used published clinical trials define disease, as well biomarker features from existing studies registries that are predictive more rapid [1, 2]. Specifically, we looked for associated skin lung [3]. performed rigorous review investigator- patient-reported outcomes hypothesis amelioration symptoms SSc. Results Progressive disease was defined having diffuse cutaneous evidence active by criteria. were similar those previous trials, but developed novel strategy using KL-6 addition C-reactive protein (CRP) erythrocyte sedimentation rate. These biomarkers identify additional at risk Significant digital ulcers or history and/or Raynaud’s phenomenon requiring medical elevated CRP. hierarchy primary, key secondary, secondary endpoints, including forced vital capacity, modified Rodnan score, revised Composite Response Index Systemic Sclerosis, Health Assessment Questionnaire-Disability Index, ulcer burden, symptom scoring, investigate decline function over 48 weeks reduce other disabilities determined sample size 100 sufficient obtain 80% power observe changes Conclusion 48-week enrolling 200 significant targeting can is now active, details available NCT05559580 . References [1]Distler O, et al. Eur Respir J 2020;55:1902026 [2]Khanna D, Lancet 2016;387:2630–2640 [3]Khanna Ann Rheum Dis 2022;81:102–103 Acknowledgements: NIL. Disclosure Interests Dinesh Khanna Shareholder of: Eicos, Speakers bureau: AbbVie, Boehringer Ingelheim, CSL Behring, Genentech, Horizon Therapeutics, Janssen, Consultant Bristol Myers Squibb, Prometheus, Talaris, Theraly, Grant/research support from: Pfizer, Mary Flack Employee Ingelheim Pharmaceuticals, Inc, Tobias Litzenburger Pharma GmbH & Co. KG, Nora Fagan Inc., Oliver Distler Bayer, Medscape, 4P-Pharma, Abbvie, Acceleron, Alcimed, Altavant Siences, Amgen, AnaMar, Arxx, AstraZeneca, Baecon, Blade, Corbus, Galapagos, Glenmark, Horizon, Inventiva, Kymera, Lupin, Miltenyi Biotec, Mitsubishi Tanabe, MSD, Novartis, Redxpharna, Roivant, Sanofi Topadur, Galderma Gossamer, iQvia, Merck, Ingelheim.