ODP103 IPN60130 for the Treatment of Fibrodysplasia Ossificans Progressiva: Methodology of the Randomized, Double-Blind, Placebo-Controlled Phase II FALKON Trial

Abstract

Abstract Objectives Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare genetic disorder caused by activin receptor-like kinase-2/activin A receptor type 1(ALK2/ACVR1) mutation and characterized by heterotopic ossification (HO) inducing progressive restriction of mobility. IPN60130 is a selective ALK2/ACVR1 inhibitor, currently being investigated for the treatment of FOP. 1 Here, we describe methodology of the FALKON trial (NCT05039515) designed to compare efficacy and safety of IPN60130 with placebo in patients with FOP. Methods Patients will be randomized to oral placebo, or low or high dose IPN60130 for 12 months; patients receiving placebo will then transition to IPN60130 for 12 months. Patients will be randomized to receive placebo, or low or high dose IPN60130 orally for 24months. Enrollment criteria include: age of ≥5years, clinical FOP diagnosis with a disease-causing mutation, and either a flare-up, new HO, new joint ankylosis, or increase in Cumulative Analogue Joint Involvement Scale (CAJIS) score in the prior year. Recruitment is ongoing to enroll 90 patients. The primary efficacy outcome will be the annualized change from Baseline (CfB) in HO volume to Month 12, assessed using low-dose whole-body computed tomography (CT). Secondary efficacy outcomes to be compared with placebo at Month 12 include: CfB in volume of new HO lesions, CfB in number of HO lesions, flare-up rate and number of flare-up days, number of body regions with new HO, CfB in pain intensity, and the proportion of patients with any new HO. Additional secondary endpoints include CfB in HO volume in treated patients versus placebo and participants receiving standard of care in a FOP natural history study (NCT02322255) at Month 24. Safety will be assessed via the incidence of adverse events (AEs) and serious AEs over 25 months. Patients aged ≥15 years will be eligible for a sub-study assessing HO using [ 18 F]NaF positron emission tomography-CT. Summary Results from the FALKON trial, expected to complete in August 2025, will enable evaluation of the efficacy and safety of IPN60130 in patients with FOP.