Browsing by Author "Colombo, Carla"

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    Safety and efficacy of lenabasum in a phase 2 randomized, placebo-controlled trial in adults with cystic fibrosis
    (Elsevier, 2021) Chmiel, James F.; Flume, Patrick; Downey, Damian G.; Dozor, Allen J.; Colombo, Carla; Mazurek, Henryk; Sapiejka, Ewa; Rachel, Marta; Constantine, Scott; Conley, Brian; Dgetluck, Nancy; Dinh, Quinn; White, Barbara; Elborn, J. Stuart; Lenabasum JBT101-CF-001 Study Group; Pediatrics, School of Medicine
    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.