Bexotegrast for treatment of idiopathic pulmonary fibrosis (BEACON-IPF): study protocol for a multinational, phase 2b/3, double-blind, randomised, multicentre, controlled trial

INTRODUCTION: in development for idiopathic pulmonary fibrosis (IPF). In the phase 2a study INTEGRIS-IPF study (NCT04396756), bexotegrast was well tolerated and showed antifibrotic activity. METHODS AND ANALYSIS: BEACON-IPF (NCT06097260) is a randomised, double-blind, placebo-controlled, dose-finding, operationally seamless, adaptive phase 2b/3 study evaluating the efficacy and safety of bexotegrast over 52 weeks in participants with IPF. The phase 2b dose selection cohort will enrol 360 participants randomised 1:1:1 to once-daily bexotegrast 160 mg, 320 mg or placebo. After enrolling the last participant in the phase 2b cohort and while conduct is ongoing, the phase 3 cohort will immediately begin enrolment with a 'seamless group' using the same 1:1:1 randomisation. Once the phase 2b cohort has completed and a dose has been selected, the remainder of the phase 3 cohort will be enrolled. Participants in the phase 2b cohort receiving the non-selected dose will be eligible for an open-label study at the selected phase 3 dose. Background therapy with pirfenidone or nintedanib is permitted in ≤70% of the study population. Participants must be adults (≥40 years), have an IPF diagnosis ≤7 years per 2018 international guidelines, per cent predicted forced vital capacity (FVCpp) ≥45% and diffusing capacity for carbon monoxide (haemoglobin adjusted) ≥30%. The primary endpoint is change from baseline in absolute FVC at week 52. Additional endpoints include safety and tolerability, time to disease progression, participant-reported symptom assessments and quantitative lung fibrosis extent. ETHICS AND DISSEMINATION: This study was approved by Advarra institutional review board (IRB; OHRP and Food and Drug Administration registration 00000971) and at each participating site by IRBs and local ethics review committees. Participants will provide written informed consent before taking part. Study results will be disseminated in peer-reviewed journals and international conferences targeted to medical, academic and patient communities. TRIAL REGISTRATION NUMBER: NCT06097260.