A Study to Examine the Safety, Tolerability and Effects on Abnormal Bone Formation of REGN2477 in Patients With Fibrodysplasia Ossificans Progressiva

Summary

This is a three period study design consisting of a 6-month, randomized, double-blind placebo-controlled treatment (period 1) followed by a 6-month, open-label treatment (period 2) and a follow-up treatment period (period 3). Primary safety objective of the study is to assess the safety and tolerability of REGN2477 in male and female patients with fibrodysplasia ossificans progressiva (FOP). Primary efficacy objective of the study is to assess the effect of REGN2477 versus placebo on the change from baseline in heterotopic ossification (HO) in patients with FOP, as determined by 18-NaF uptake in HO lesions by positron emission tomography (PET) and in total volume of HO lesions by computed tomography (CT). Key Secondary objectives are: * To compare the effect of REGN2477 versus placebo on pain due to FOP, as measured by the area under the curve (AUC) for pain based on daily pain numeric rating scale (NRS) scores * To assess the effect of REGN2477 versus placebo on the change from baseline in HO, as determined by the number of new HO lesions identified by 18F-NaF PET or by CT * To assess the effect of REGN2477 versus placebo on the change from baseline in 18F-NaF standardized uptake value maximum (SUVmax) of individual active HO site(s) by PET * To assess the effect of REGN2477, between week 28 and week 56, on the number, activity, and volume of HO lesions identified by 18F-NaF PET or by CT in patients who switch from placebo to REGN2477 at week 28 versus the same patients between baseline and week 28 * To assess the effect of REGN2477 versus placebo on the change from baseline in biochemical markers of bone formation * To characterize the concentrations of total activin A at baseline and over time following the first dose of study drug * To characterize the concentration-time profile (pharmacokinetics \[PK\]) of REGN2477 in patients with FOP * To assess the immunogenicity of REGN2477

Timeline

Start

2018-02-26

Primary completion

2019-09-16

Completion

2021-09-16

Publications

• Baldasaro J, Sanchez RJ, Hartford C, Dahir KM, Keen R, Funck-Brentano T, Pignolo RJ, Davis M, Altman DE. Content Validation of the Flares Diary: A Qualitative Analysis of the Flares Experience Within the Fibrodysplasia Ossificans Progressiva (FOP) Population. Adv Ther. 2026 Apr;43(4):1827-1844. doi: 10.1007/s12325-026-03506-6. Epub 2026 Mar 10.
• de Ruiter RD, Botman E, Teunissen BP, Lammertsma AA, Boellaard R, Raijmakers PG, Schwarte LA, Nieuwenhuijzen JA, Gonzalez Trotter D, Eekhoff EMW, Yaqub M. Performance of simplified methods for quantification of [18F]NaF uptake in fibrodysplasia ossificans progressiva. Front Nucl Med. 2024 Jul 22;4:1406947. doi: 10.3389/fnume.2024.1406947. eCollection 2024.
• Keen R, Dahir KM, McGinniss J, Sanchez RJ, Mellis S, Economides AN, Di Rocco M, Orcel P, Roux C, Tabarkiewicz J, Bachiller-Corral J, Cheung AM, Al Mukaddam M, Mohammadi K, Gu J, Srinivasan D, Trotter DG, Eekhoff EMW, Kaplan FS, Pignolo RJ. Characterization of flare-ups and impact of garetosmab in adults with fibrodysplasia ossificans progressiva: a post hoc analysis of the randomized, double-blind, placebo-controlled LUMINA-1 trial. J Bone Miner Res. 2024 Sep 26;39(10):1486-1492. doi: 10.1093/jbmr/zjae140.
• Di Rocco M, Forleo-Neto E, Pignolo RJ, Keen R, Orcel P, Funck-Brentano T, Roux C, Kolta S, Madeo A, Bubbear JS, Tabarkiewicz J, Szczepanek M, Bachiller-Corral J, Cheung AM, Dahir KM, Botman E, Raijmakers PG, Al Mukaddam M, Tile L, Portal-Celhay C, Sarkar N, Hou P, Musser BJ, Boyapati A, Mohammadi K, Mellis SJ, Rankin AJ, Economides AN, Trotter DG, Herman GA, O'Meara SJ, DelGizzi R, Weinreich DM, Yancopoulos GD, Eekhoff EMW, Kaplan FS. Garetosmab in fibrodysplasia ossificans progressiva: a randomized, double-blind, placebo-controlled phase 2 trial. Nat Med. 2023 Oct;29(10):2615-2624. doi: 10.1038/s41591-023-02561-8. Epub 2023 Sep 28.
• Vanhoutte F, Liang S, Ruddy M, Zhao A, Drewery T, Wang Y, DelGizzi R, Forleo-Neto E, Rajadhyaksha M, Herman G, Davis JD. Pharmacokinetics and Pharmacodynamics of Garetosmab (Anti-Activin A): Results From a First-in-Human Phase 1 Study. J Clin Pharmacol. 2020 Nov;60(11):1424-1431. doi: 10.1002/jcph.1638. Epub 2020 Jun 18.
• Aykul S, Corpina RA, Goebel EJ, Cunanan CJ, Dimitriou A, Kim HJ, Zhang Q, Rafique A, Leidich R, Wang X, McClain J, Jimenez J, Nannuru KC, Rothman NJ, Lees-Shepard JB, Martinez-Hackert E, Murphy AJ, Thompson TB, Economides AN, Idone V. Activin A forms a non-signaling complex with ACVR1 and type II Activin/BMP receptors via its finger 2 tip loop. Elife. 2020 Jun 9;9:e54582. doi: 10.7554/eLife.54582.

Drugs

Indications