VERANDA-SSc: study design of a phase III, randomised, placebo-controlled trial evaluating the efficacy and safety of oral nerandomilast treatment in systemic sclerosis
Year: 2026
Type: article
Study design: Study Protocol
Abstract: Introduction: Systemic sclerosis (SSc) is a rare, heterogeneous, autoimmune disease. It involves a complex interplay of immune dysregulation, vasculopathy and fibrosis. There are no widely approved drugs that target all three underlying mechanisms and modify the overall SSc disease course or prevent overall disease progression. Nerandomilast, a preferential phosphodiesterase 4B inhibitor, has demonstrated antifibrotic, immunomodulatory and vasculoprotective effects in models relevant to SSc. The phase III VERANDA-SSc trial (NCT07497087) will investigate the efficacy and safety of nerandomilast in patients with SSc. Methods and analysis: This double-blind, randomised, placebo-controlled trial will be conducted at ~235 sites across 45 countries. Approximately 450 patients with SSc will be randomised 1:1 to receive 18 mg nerandomilast two times a day or placebo in addition to standard-of-care therapy. The dose may be reduced to 9 mg two times a day or interrupted based on individual tolerability or if used concomitantly with strong CYP3A inhibitors. Treatment will continue for at least 52 weeks and until the planned number of primary endpoint events is reached.Adult patients must meet the 2013 American College of Rheumatology/European Alliance of Associations for Rheumatology classification criteria, have disease onset within 7 years and have active disease (key inclusion criteria permit the enrolment of patients with diffuse cutaneous or limited cutaneous SSc). Stable background immunosuppressive or nintedanib therapy is allowed.The primary endpoint is a composite of time to the first occurrence of predefined SSc-related clinically meaningful disease progression or complications, or confirmed absolute decline in forced vital capacity % predicted ≥5% (for patients with interstitial lung disease at baseline), or relative increase in modified Rodnan skin score (mRSS) ≥25% together with an absolute increase in mRSS ≥5 points, or all-cause death. Safety, pharmacokinetics, organ manifestations and patient-reported outcomes will also be assessed. Trial registration number: NCT07497087.
Institutions: Oslo University Hospital, University of Zurich, University Hospital Zurich, Inserm, Université Paris Cité, University of Leeds, University College London, Nippon Medical School, University of Michigan, The University of Texas Health Science Center at Houston, University of California, Los Angeles, Boehringer Ingelheim (United States), Boehringer Ingelheim (Germany), Boehringer Ingelheim (Switzerland)
Language: English
Subfield: Rheumatology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,150
OpenAlex ID: W7225081337