VERANDA-SSc: study design of a phase III, randomised, placebo-controlled trial evaluating the efficacy and safety of oral nerandomilast treatment in systemic sclerosis
12 affiliations
- 1Oslo University Hospital, Oslo, Norway
- 2Department of Rheumatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
- 3Rheumatology Department, Saint Joseph Hospital, Université Paris Cité, INSERM U1016, Paris, France
- 4NIHR Biomedical Research Centre and Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK
- 5UCL Medical School, London, UK
- 6Nippon Medical School, Tokyo, Japan
- 7University of Michigan, Ann Arbor, Michigan, USA
- 8UTHealth Houston, Houston, Texas, USA
- 9University of California, Los Angeles, California, USA
- 10Boehringer Ingelheim Pharmaceuticals, Inc, Ridgefield, Connecticut, USA
- 11Boehringer Ingelheim International GmbH, Ingelheim am Rhein, Germany
- 12Boehringer Ingelheim (Schweiz) GmbH, Basel, Switzerland
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.
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BibTeX
@article{hoffmannvold2026verandassc,
title = {{VERANDA-SSc: study design of a phase III, randomised, placebo-controlled trial evaluating the efficacy and safety of oral nerandomilast treatment in systemic sclerosis}},
author = {Anna-Maria Hoffmann-Vold and Oliver Distler and Yannick Allanore and Francesco Del Galdo and Christopher P Denton and Masataka Kuwana and Dinesh Khanna and Zsuzsanna H McMahan and Elizabeth R Volkmann and Hao Li and Mihaela Dumistracel and Martina Gahlemann and Susanne Stowasser and Shervin Assassi},
journal = {Journal of Scleroderma and Related Disorders},
year = {2026},
month = nov,
doi = {10.1136/jsrd-2026-000052},
url = {https://doi.org/10.1136/jsrd-2026-000052},
note = {CC BY-NC 4.0},
}
RIS
TY - JOUR
TI - VERANDA-SSc: study design of a phase III, randomised, placebo-controlled trial evaluating the efficacy and safety of oral nerandomilast treatment in systemic sclerosis
AU - Anna-Maria Hoffmann-Vold
AU - Oliver Distler
AU - Yannick Allanore
AU - Francesco Del Galdo
AU - Christopher P Denton
AU - Masataka Kuwana
AU - Dinesh Khanna
AU - Zsuzsanna H McMahan
AU - Elizabeth R Volkmann
AU - Hao Li
AU - Mihaela Dumistracel
AU - Martina Gahlemann
AU - Susanne Stowasser
AU - Shervin Assassi
PY - 2026
DA - 2026/11/02
JO - Journal of Scleroderma and Related Disorders
DO - 10.1136/jsrd-2026-000052
UR - https://doi.org/10.1136/jsrd-2026-000052
AB - 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.
SN - 2397-1983
SN - 2397-1991
ER -