Design of an open-label extension trial of nerandomilast (BI 1015550) in patients with idiopathic pulmonary fibrosis and progressive pulmonary fibrosis (FIBRONEER™-ON)

Abstract Background There is a need for more effective treatments for idiopathic pulmonary fibrosis (IPF) and progressive pulmonary fibrosis (PPF). Nerandomilast (BI 1015550), an oral preferential inhibitor of phosphodiesterase 4B, is being evaluated in two randomized Phase III trials: FIBRONEER™-IPF (NCT05321069) and FIBRONEER™-ILD (NCT05321082). FIBRONEER™-ON is an open-label extension (OLE) of these studies that will evaluate the long-term safety and efficacy of nerandomilast. Here, we describe the study design of the OLE. Methods This prospective 98-week OLE will follow the Phase III parent trials, which are currently underway with 1177 patients enrolled in FIBRONEER™-IPF and 1178 patients enrolled in FIBRONEER™-ILD. Approximately 1700 patients from 44 countries are expected to complete the parent trials and will be eligible for continuing into the OLE; this estimate assumes that there will be a discontinuation rate of ~25% over the duration of the parent trials and > 90% of eligible patients will agree to participate in the OLE. Irrespective of whether previously on active treatment or placebo, all patients in the OLE will be treated with nerandomilast at either 9 mg or 18 mg twice daily, depending on which dose demonstrates the most favorable benefit–risk profile in the parent trials. The primary endpoint will be the occurrence of any adverse event over the course of the OLE. This trial will also monitor long-term efficacy outcomes, including forced vital capacity change, and time to first exacerbation, disease progression, hospitalization and death. Discussion This trial will provide information on the long-term safety, tolerability and efficacy of nerandomilast in patients with IPF and PPF. Trial registration FIBRONEER™-ON: ClinicalTrials.gov: NCT06238622, registered 2 February 2024. Protocol version and date: version 3.0, 29 Apr 2024. FIBRONEER™-IPF: ClinicalTrials.gov: NCT05321069, registered 11 March 2022.FIBRONEER™-ILD: ClinicalTrials.gov: NCT05321082, registered 11 March 2022.