Evidence map›Paper›PMID 40088930›Full record

Trial reportRheumatology (Oxford, England)2025

Belumosudil in diffuse cutaneous systemic sclerosis: a randomized, double-blind, open-label extension, placebo-controlled, phase 2 study.

Lorinda Chung, Richard M Silver, Virginia Steen, Daniel E Furst, Flavia V Castelino, Marcin Trojanowski, Robert Spiera, Robyn Domsic, Alicia Rodriguez-Pla, Tamiko R Katsumoto and 5 more

Registry-linked trialAbstract readRandomized Controlled TrialClinical Trial, Phase IIMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Rheumatology (Oxford, England), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03919799 (A Phase 2, Randomized, Placebo-controlled, Double-blind, Open-label Extension Multicenter Study to Evaluate the Efficacy and Safety of Belumosudil), which is not on this map. Cited by 2 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT03919799 phase2terminatednot on this map

A Phase 2, Randomized, Placebo-controlled, Double-blind, Open-label Extension Multicenter Study to Evaluate the Efficacy and Safety of Belumosudil (KD025) in Subjects With Diffuse Cutaneous Systemic Sclerosis

TypeinterventionalSponsorKadmon, a Sanofi CompanyRan2019 to 2023Enrolled36ConditionsSystem, Sclerosis, Diffuse Cutaneous Systemic SclerosisArmsBelumosudil (KD025), Placebo
3 · Its place in the literature

Who cites it

2 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors.

Lorinda ChungDepartment of Medicine and Dermatology, Stanford University School of Medicine, Stanford, CA, USA.ORCID 0000-0003-0072-6939
Richard M SilverDepartment of Medicine, Medical University of South Carolina (MUSC), Charleston, SC, USA.
Virginia SteenDepartment of Medicine, Georgetown University, Washington, DC, USA.
Daniel E FurstSouthern California Scleroderma and Rheumatology Centre, Los Angeles, CA, USA.ORCID 0000-0001-7857-2373
Flavia V CastelinoDivision of Rheumatology, Massachusetts General Hospital (MGH), Boston, MA, USA.
Marcin TrojanowskiDepartment of Medicine, Boston University, Boston, MA, USA.
Robert SpieraDepartment of Medicine, Hospital of Special Surgery, New York, NY, USA.
Robyn DomsicDivision of Rheumatology, Department of Internal Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.ORCID 0000-0002-2765-0922
Alicia Rodriguez-PlaDivision of Rheumatology, Mayo Clinic, Scottsdale, AZ, USA.
Tamiko R KatsumotoDepartment of Medicine and Dermatology, Stanford University School of Medicine, Stanford, CA, USA.ORCID 0000-0002-7978-0315
Helene GoulaouicSanofi, Chilly-Mazarin, France.
Hong WangSanofi, Cambridge, MA, USA.
Melanie EspinasseSanofi, Chilly-Mazarin, France.
Souheil El-ChemalySanofi, Cambridge, MA, USA.
Rui WangSanofi, Cambridge, MA, USA.ORCID 0009-0000-1622-2802

Funding

AstraZenecaEicos Sciences and Formation BiologicsFormation Biologics and NovartisNational Scleroderma FoundationNIHSanofi
6 · The paper itself

Abstract

objectivesTo determine the efficacy, safety and pharmacodynamics of belumosudil in patients with diffuse cutaneous systemic sclerosis (dcSSc) treated with background immunosuppressive therapies.

methodsEligible patients were randomised 1:1:1 to receive belumosudil 200 mg once daily (QD) or twice daily (BID), or placebo for 28 weeks (double-blind period). After unblinding, the patients who received belumosudil continued the same dose, whereas the patients who received placebo were re-randomised for one of the belumosudil doses for 24 weeks (open-label extension).

resultsThirty-five and 31 patients were treated in the double-blind and open-label periods, respectively. The study was terminated prematurely, and target enrolment was not met. The primary end point, of CRISS score ≥0.60 at week 24, did not exhibit an efficacy signal in the belumosudil vs placebo groups [odds ratio: 1.06 (0.19-5.82; P = 0.9472) for the QD, and 0.39 (0.07-2.35; P = 0.3078) for the BID group]. Belumosudil was well tolerated and exhibited similar safety profiles in both double-blind and open-label periods. Tissue-based RNA sequencing analysis revealed FOXP3 upregulation and STAT3, IL23A and TGF-β downregulation in patients with CRISS score ≥0.60, which supported the mechanism of action of belumosudil. In blood and tissue samples, trends of decreased fibrosis biomarker levels were seen in the belumosudil-treated group vs placebo.

conclusionEfficacy signal for belumosudil could not be detected. Signalling pathway modulation analysis supported the mechanism of action of belumosudil. A trend for decreased fibrosis-related biomarkers was observed in the belumosudil-treated group.

trial registrationClinicalTrials.gov, https://clinicaltrials.gov, NCT03919799.

Indexed as

Protein Kinase InhibitorsScleroderma, DiffuseAcetamidesAdultAgedDouble-Blind MethodFemaleHumansImmunosuppressive AgentsMaleMiddle AgedTreatment OutcomeAcetamidesbelumosudilImmunosuppressive AgentsProtein Kinase Inhibitorsbelumosudilbiomarkerclinical trialCRISSdiffuse cutaneous systemic sclerosis

Identifiers

PMID40088930
PMCPMC12212915

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.