PT - JOURNAL ARTICLE AU - Christopher H. Goss AU - Raksha Jain AU - Wolfgang Seibold AU - Anne-Caroline Picard AU - Ming-Chi Hsu AU - Abhya Gupta AU - Isabelle Fajac TI - An innovative Phase II trial to establish proof of efficacy and optimal dose of a new inhaled ENaC inhibitor BI 1265162 in adults and adolescents with cystic fibrosis (BALANCE-CF™ 1) AID - 10.1183/23120541.00395-2020 DP - 2020 Jan 01 TA - ERJ Open Research PG - 00395-2020 4099 - http://openres.ersjournals.com/content/early/2020/09/24/23120541.00395-2020.short 4100 - http://openres.ersjournals.com/content/early/2020/09/24/23120541.00395-2020.full AB - Inhibition of the epithelial sodium channel (ENaC) represents an important, mutation-agnostic therapeutic approach to restore airway surface liquid in patients with cystic fibrosis (CF). A Phase II trial of the ENaC inhibitor BI 1265162, inhaled via the Respimat® Soft Mist™ inhaler, in patients aged ≥12 years with CF is being conducted to assess the efficacy and safety of BI 1265162, on top of standard CF treatment (NCT04059094).BALANCE-CF™ 1 is a multinational, randomised, double-blind, placebo-controlled, parallel-group, dose-ranging trial consisting of 2 weeks’ screening, 4 weeks’ randomised treatment and 1 week follow-up. Ninety-eight patients, including ≥21 adolescents, will be randomised. First, 28 patients will be allocated to the highest dose of BI 1265162 (200 µg twice daily [BID]) or placebo in a 1:1 ratio. The remaining 70 patients will be allocated to one of five treatment arms (200 µg, 100 µg, 50 µg, 20 µg or placebo BID), with a final distribution ratio of 2:1:1:1:2. Recruitment and randomisation will begin with adult patients. An independent Data Monitoring Committee will review safety data to advise on inclusion of adolescents and study continuation. A futility analysis will be conducted after 28 patients to prevent exposure of further patients in case of insufficient evidence of clinical efficacy. The design ensures that potential for effect is assessed ahead of wider enrolment, allowing investigation of a dose-response effect with minimal patient numbers.The results will increase understanding of efficacy, safety and optimal dosing of the inhaled ENaC inhibitor BI 1265162 in adults and adolescents with CF.FootnotesThis manuscript has recently been accepted for publication in the ERJ Open Research. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJOR online. Please open or download the PDF to view this article.Conflict of interest: C.H. Goss reports funding for conducting exacerbation studies in cystic fibrosis (CF) from the Cystic Fibrosis Foundation, funding to study the role of microbiome in the treatment of exacerbation in CF from the European Commission, funding to conduct a study of home monitoring in pulmonary exacerbation from the NIH (NHLBI), and funding to support clinical research in cystic fibrosis and clinical trials in other disease entities from the NIH (NIDDK and NCRR), during the conduct of the study; personal fees for serving as a Chair of a Grant Review Committee from Gilead Sciences, personal fees for serving as a DSMB Chair for a trial supported by Novartis and the European Commission from Novartis, funding to study a novel antimicrobial in CF from the NIH and the FDA, serving a US lead in a phase 2 trial of novel therapy for CF, receiving travel expenses and an honorarium for meeting participation, and a future site contract for trial participation from Boehringer Ingelheim, and honoraria and travel expenses for talk at Nottingham LEAD conference from Vertex Pharmaceuticals, outside the submitted work. None of the work presented in this opinion piece were influenced by the funding sources noted above. The funding sources that support other ongoing research played no role in writing this manuscript or in the decision to submit for publication.Conflict of interest: Dr. Jain reports grants and personal fees from Vertex Pharmaceuticals, personal fees from Gilead Sciences, grants from CF Foundation, outside the submitted work.Conflict of interest: W. Seibold is an employee of BI.Conflict of interest: Dr. Picard is an employee of Boehringer Ingelheim International GmbH.Conflict of interest: Dr. HSU has nothing to disclose.Conflict of interest: A. Gupta is an employee of Boehringer Ingelheim International GmbH.Conflict of interest: I. Fajac reports grants and personal fees for study conduct and expert advice from Boehringer during the conduct of the study, and from Proteostasis Therapeutics and Vertex Pharmaceuticals outside the submitted work.