A Study to Examine the Safety, Tolerability and Effects on Abnormal Bone Formation of REGN2477 in Patients With Fibrodysplasia Ossificans Progressiva
NCT ID: NCT03188666
Last Updated: 2022-12-02
Study Results
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View full resultsBasic Information
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COMPLETED
PHASE2
44 participants
INTERVENTIONAL
2018-02-26
2021-09-16
Brief Summary
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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
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Detailed Description
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Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
QUADRUPLE
Study Groups
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REGN2477
REGN2477
Pharmaceutical form: liquid product for injection/infusion; Route of administration: Intravenous (IV); Administered during treatment periods 1 and 2.
Placebo
Matching placebo
Pharmaceutical form: Liquid product for injection/infusion; Route of administration: Intravenous (IV); Administered during treatment period 1 only.
Interventions
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REGN2477
Pharmaceutical form: liquid product for injection/infusion; Route of administration: Intravenous (IV); Administered during treatment periods 1 and 2.
Matching placebo
Pharmaceutical form: Liquid product for injection/infusion; Route of administration: Intravenous (IV); Administered during treatment period 1 only.
Eligibility Criteria
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Inclusion Criteria
* Clinical diagnosis of FOP (based on findings of congenital malformation of the great toes, episodic soft tissue swelling, and/or progressive heterotopic ossification (HO)).
* Confirmation of FOP diagnosis with documentation of any ACVR1 mutation.
* FOP disease activity within 1 year of screening visit. FOP disease activity is defined as pain, swelling, stiffness, and other signs and symptoms associated with FOP flare-ups; or worsening of joint function, or radiographic progression of heterotopic ossifications (increase in site or number of HO lesions) with/without being associated with flare-up episodes.
* Willing and able to undergo PET and CT imaging procedures and other procedures as defined in this study.
Exclusion Criteria
* Previous history or diagnosis of cancer.
* Use of bisphosphonate within 1 year of screening.
* Concurrent participation in another interventional clinical study, or a non-interventional study with radiographic measures or invasive procedures (e.g. collection of blood or tissue samples). Participation in the FOP Connection Registry or other studies in which participants complete study questionnaires are allowed.
* Treatment with another investigational drug, denosumab, imatinib or isotretinoin in the last 30 days or within 5 half-lives of the investigational drug, whichever is longer.
* Pregnant or breastfeeding women.
* Male and women of childbearing potential participants who are unwilling to practice highly effective contraception.
18 Years
60 Years
ALL
No
Sponsors
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Regeneron Pharmaceuticals
INDUSTRY
Responsible Party
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Principal Investigators
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Clinical Trial Management
Role: STUDY_DIRECTOR
Regeneron Pharmaceuticals
Locations
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Mayo Clinic
Rochester, Minnesota, United States
University of Pennsylvania
Philadelphia, Pennsylvania, United States
Vanderbilt University
Nashville, Tennessee, United States
Toronto General Hospital
Toronto, Ontario, Canada
Hopital Cochin
Paris, , France
Hopital Lariboisiere,Hospitalier Universitaire Nord
Paris, , France
Giannina Gaslini Institute
Genova, , Italy
VU University Medical Center
Amsterdam, North Holland, Netherlands
Szpital Wojewodzki Nr 2
Rzeszów, , Poland
Hospital Universitario Ramon y Cajal
Madrid, , Spain
Royal National Orthopaedic Hospital, Brockley Hill
Stanmore, Middlesex, United Kingdom
Countries
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References
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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.
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.
Provided Documents
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Document Type: Study Protocol
Document Type: Statistical Analysis Plan
Other Identifiers
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2016-005035-33
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
R2477-FOP-1623
Identifier Type: -
Identifier Source: org_study_id
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