Safety and efficacy of lenabasum in a phase 2 randomized, placebo-controlled trial in adults with cystic fibrosis
dc.contributor.author | Chmiel, James F. | |
dc.contributor.author | Flume, Patrick | |
dc.contributor.author | Downey, Damian G. | |
dc.contributor.author | Dozor, Allen J. | |
dc.contributor.author | Colombo, Carla | |
dc.contributor.author | Mazurek, Henryk | |
dc.contributor.author | Sapiejka, Ewa | |
dc.contributor.author | Rachel, Marta | |
dc.contributor.author | Constantine, Scott | |
dc.contributor.author | Conley, Brian | |
dc.contributor.author | Dgetluck, Nancy | |
dc.contributor.author | Dinh, Quinn | |
dc.contributor.author | White, Barbara | |
dc.contributor.author | Elborn, J. Stuart | |
dc.contributor.author | Lenabasum JBT101-CF-001 Study Group | |
dc.contributor.department | Pediatrics, School of Medicine | |
dc.date.accessioned | 2024-08-16T10:43:26Z | |
dc.date.available | 2024-08-16T10:43:26Z | |
dc.date.issued | 2021 | |
dc.description.abstract | Background: Few therapies specifically address the chronic airway inflammation in cystic fibrosis (CF) that contributes to progressive destruction of lung tissue and loss of lung function. Lenabasum is a cannabinoid type 2 receptor (CB2) agonist that resolves inflammation in a number of in vitro and in vivo models. Methods: A Phase 2 double-blind, randomized, placebo-controlled study assessed the safety and tolerability of lenabasum in adults with CF. Subjects with FEV1% (ppFEV1) ≥40% predicted were randomized to lenabasum 1 or 5 mg or placebo once daily (QD) (Weeks 1-4), then 20 mg QD, 20 mg twice daily (BID) or placebo (Weeks 5-12), with follow-up at Week 16. Pulmonary exacerbations (PEx) were recorded and biomarkers of blood and lung inflammation were measured. Results: Of 89 subjects randomized, 51 lenabasum and 23 placebo-only subjects completed the study. No deaths or serious or severe adverse events (AE) were considered related to lenabasum. Most AEs were mild/moderate, and the most common were PEx, hemoptysis, dry mouth, and upper respiratory infection. Three lenabasum and one placebo-only subjects discontinued the study for a treatment related AE. New PEx were treated with intravenous antibiotics in 4.0% of lenabasum-treated vs. 11.4% of placebo-treated subjects, during Weeks 1-4 and 5.2% compared to 13.0% during Weeks 5-12 (p<0.2). No significant differences in ppFEV1 were observed between treatment groups. Sputum neutrophils, eosinophils, and neutrophil elastase were numerically reduced, and significant (p<0.05) reductions in IL-8 and immunoglobulin G levels occurred with lenabasum. Conclusions: The safety findings of lenabasum, coupled with biomarker data, support further testing in a larger study with a longer duration. | |
dc.eprint.version | Final published version | |
dc.identifier.citation | Chmiel JF, Flume P, Downey DG, et al. Safety and efficacy of lenabasum in a phase 2 randomized, placebo-controlled trial in adults with cystic fibrosis. J Cyst Fibros. 2021;20(1):78-85. doi:10.1016/j.jcf.2020.09.008 | |
dc.identifier.uri | https://hdl.handle.net/1805/42822 | |
dc.language.iso | en_US | |
dc.publisher | Elsevier | |
dc.relation.isversionof | 10.1016/j.jcf.2020.09.008 | |
dc.relation.journal | Journal of Cystic Fibrosis | |
dc.rights | Publisher Policy | |
dc.source | Publisher | |
dc.subject | Cystic fibrosis | |
dc.subject | Lenabasum | |
dc.subject | Pulmonary exacerbations | |
dc.subject | Safety | |
dc.title | Safety and efficacy of lenabasum in a phase 2 randomized, placebo-controlled trial in adults with cystic fibrosis | |
dc.type | Article |