Aerosolized lancovutide in adolescents (≥12 years) and adults with cystic fibrosis - a randomized trial
Ernst Eber, Maria Trawinska-Bartnicka, Dorota Sands, Gabriel Bellon, Uwe Mellies, Katalin Bolbás, Serena Quattrucci, Henryk Mazurek, Rudolf Widmann, Christian Schoergenhofer, Bernd Jilma, Felix Ratjen, Ernst Eber, Maria Trawinska-Bartnicka, Dorota Sands, Gabriel Bellon, Uwe Mellies, Katalin Bolbás, Serena Quattrucci, Henryk Mazurek, Rudolf Widmann, Christian Schoergenhofer, Bernd Jilma, Felix Ratjen
Abstract
Background: Lancovutide activates a chloride channel (TMEM-16A) other than the cystic fibrosis (CF) transmembrane conductance regulator protein and could benefit CF patients.
Methods: In this randomized, multi-center, double-blind, placebo-controlled, parallel-group trial 161 patients ≥12 years with a confirmed diagnosis of CF were randomized to either placebo (saline) or active drug in 3 different dosing schemes of 2.5mg inhaled lancovutide (once daily, every other day or twice a week) for eight weeks. The primary endpoint was the change in the forced expiratory volume in 1 second (FEV1) percent predicted. Secondary endpoints included further lung function parameters (FEV1 (absolute), functional vital capacity percent predicted, forced expiratory flow percent predicted, pulse oximetry), quality of life assessment, pulmonary exacerbations, hospitalization due to pulmonary exacerbations, time to first pulmonary exacerbation, duration of anti-inflammatory, mucolytic or antibiotic treatment, and safety.
Results: There was no significant difference in the change in FEV1 percent predicted, quality of life, other lung function parameters, pulmonary exacerbations or requirement of additional treatment between groups. Overall, the inhalation of lancovutide was safe although a higher rate of adverse events, especially related to the respiratory system, occurred as compared to placebo.
Conclusions: Lancovutide did not improve FEV1 percent predicted when compared to placebo (NCT00671736).
Keywords: Clinical trial; Cystic fibrosis; Lancovutide; Lung function; Quality of life.
Conflict of interest statement
Declaration of Competing Interest RW is founder and employee of AOP Orphan Pharmaceuticals AG. EE reports receiving consultancy fees from Vertex Pharmaceuticals, Chiesi Pharmaceuticals, Gilead Sciences, Vifor, and Insmed, and speaker's honoraria from Vertex Pharmaceuticals, Chiesi Pharmaceuticals, and Gilead Sciences. Dr. Ratjen reports grants and personal fees from Vertex, personal fees from Proteostasis, personal fees from Bayer, personal fees from TranslateBio, personal fees from Genentech, personal fees from Boehringer Ingelheim, personal fees from Calithera, outside the submitted work. All other authors report no relevant conflicts of interest regarding this work.
Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.
Source: PubMed