Dual αvβ6 and αvβ1 Inhibition over 12 Weeks Reduces Active Type I Collagen Deposition in Individuals with Idiopathic Pulmonary Fibrosis: A Phase 2, Double-Blind, Placebo-controlled Clinical Trial
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Le résumé fourni par la source
Abstract Rationale Idiopathic pulmonary fibrosis (IPF) is characterized by excessive deposition of type I collagen. 68Ga-CBP8, a type I collagen positron emission tomography probe, measures collagen accumulation and shows higher collagen deposition in patients with IPF. Bexotegrast (PLN-74809) is an oral, once-daily, dual-selective inhibitor of αvβ6 and αvβ1 integrins under late-stage evaluation for treatment of IPF. Objectives To evaluate changes in type I collagen in the lungs of participants with IPF after treatment with bexotegrast. Methods In this phase 2 (NCT05621252), single-center, double-blind, placebo-controlled study, adults with IPF received bexotegrast 160 mg or placebo for 12 weeks. The primary endpoint was the change in whole-lung standardized uptake value of 68Ga-CBP8 positron emission tomography. Changes in lung dynamic contrast-enhanced magnetic resonance imaging parameters, FVC, cough severity, and biomarkers of collagen synthesis and progressive disease were also assessed. Measurements and Main Results Of 10 participants, 7 received bexotegrast and 3 received placebo. At Week 12, the mean change from baseline in the top quartile of 68Ga-CBP8 whole-lung standardized uptake value was −1.2% with bexotegrast versus 6.6% with placebo; the greatest mean changes were observed in subpleural lung regions in both groups (bexotegrast, −3.7%; placebo, 10.3%). Dynamic contrast-enhanced magnetic resonance imaging showed numerically increased peak enhancement and faster contrast washout rate in bexotegrast-treated participants, suggesting improvements in lung microvasculature and decreased extravascular extracellular volume. Bexotegrast treatment resulted in numerical improvements in FVC, cough severity, and biomarkers. Conclusions The reduced uptake of 68Ga-CBP8 in the lungs of participants with IPF indicates an antifibrotic effect of bexotegrast, suggesting the potential for favorable lung remodeling.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Dual αvβ6 and αvβ1 Inhibition over 12 Weeks Reduces Active Type I Collagen Deposition in Individuals with Idiopathic Pulmonary Fibrosis: A Phase 2, Double-Blind, Placebo-controlled Clinical Trial
- Date Crossref
- 01/07/2025
- Éditeur
- Oxford University Press (OUP)
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Harvard University pays non établi dans la noticeUniversité ou école supérieure
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Massachusetts General Hospital Department of Radiology pays non établi dans la noticeÉtablissement de santé
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Pulmonary and Critical Care Associates pays non établi dans la noticeÉtablissement de santé
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Pliant (United States) pays non établi dans la noticeEntreprise
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Athinoula A. Martinos Center for Biomedical Imaging pays non établi dans la noticeStructure de recherche
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Divison of Pulmonary and Critical Care Medicine and pays non établi dans la noticeInstitution
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Harvard Medical School pays non établi dans la noticeInstitution
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Inc. Pliant Therapeutics pays non établi dans la noticeEntreprise
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Pliant Therapeutics Inc pays non établi dans la noticeEntreprise
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Institute for Innovation in Imaging pays non établi dans la noticeStructure de recherche
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Athinoula A Martinos Center for Biomedical Imaging pays non établi dans la noticeInstitution
Harvard University, Department of Radiology — Massachusetts General Hospital et Pulmonary and Critical Care Associates, avec 8 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.