A Natural History Study of Fibrodysplasia Ossificans Progressiva (FOP)

NCT02322255 | Completed

• 1 other identifier: PVO-1A-001
• Study Type: observational
• Target: 114
• Locations: 6 countries
• Sites: 7

Brief Summary

Fibrodysplasia Ossificans Progressiva (FOP) is a rare, severely disabling disease characterized by painful, recurrent episodes of soft tissue swelling (flare-ups) that result in abnormal bone formation in muscles, tendons, and ligaments. Flare-ups begin early in life and may occur spontaneously or after soft tissue trauma, vaccinations, or influenza infections. Recurrent flare-ups progressively restrict movement by locking joints leading to cumulative loss of function and disability. This 3-year, non-interventional, two-part, natural history study is designed to gain insight into total body HO, FOP disease progression, the impact of FOP on subjects' physical functioning, and clinical features and biomarkers that may be useful in the diagnosis and monitoring of disease progression. This natural history study will also provide important information to inform the design of subsequent interventional trials.

Conditions

Fibrodysplasia Ossificans Progressiva

Keywords

Natural History Study; Non-interventional Study; Observational Study; Heterotopic ossification; Fibrodysplasia Ossificans Progressiva; FOP disease progression; FOP flare-up progression; Clementia; Myositosis Ossificans Progressiva; Munchmeyer's Disease; FOP; Palovarotene

Outcome Measures

Primary Outcomes (1)

• Change from baseline in the total body burden of heterotopic ossification as assessed by the optimal imaging modality (low-dose whole body CT [excluding head]).

  Month 36

Secondary Outcomes (11)

• Change from baseline in physical function as assessed by range of motion.

  Month 12, Month 24, and Month 36

• Change from baseline in patient-reported use of assistive devices and adaptations.

  Month 6, Month 12, Month 18, Month 24, Month 30, and Month 36

• Change from baseline in a disease-specific patient-reported outcome measure (FOP-Physical Function Questionnaire [FOP-PFQ]).

  Month 6, Month 12, Month 18, Month 24, Month 30, and Month 36

• Change from baseline in a patient-reported measure of physical and mental health (PROMIS Global Health Scale).

  Month 6, Month 12, Month 18, Month 24, Month 30, and Month 36

• Change from baseline in biomarkers.

  Month 12, Month 24, and Month 36

Study Arms (1)

All Subjects

All subjects enrolled in the study.

Eligibility Criteria

• Age: Up to 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Individuals with classic FOP (R206H mutation).

You may qualify if:

• \- Subjects clinically diagnosed with classical FOP with documented R206H mutation or believed to carry the R206H mutation

You may not qualify if:

• \- Participation in an interventional clinical research study within the 4 weeks prior to enrollment

Sponsors & Collaborators

• Clementia Pharmaceuticals Inc.: lead

Study Sites (7)

University of California San Francisco, Division of Endocrinology and Metabolism

San Francisco, California, 94143, United States

Location

University of Pennsylvania, Center for FOP & Related Bone Disorders

Philadelphia, Pennsylvania, 19104, United States

Location

Hospital Italiano de Buenos Aires, Department of Pediatrics

Buenos Aires, Argentina

Location

Queensland University of Technology (QUT) Institute of Health and Biomedical Innovation (IHBI)

Woolloongabba, Queensland, 4102, Australia

Location

Hôpital Necker-Enfants Malades, Department of Genetics

Paris, France

Location

Gaslini Institute, Unit of Rare Diseases, Department of Pediatrics

Genoa, Italy

Location

The Royal National Orthopaedic Hospital, Brockley Hill

Stanmore, Middlesex, HA7 4LP, United Kingdom

Location

Related Publications (11)

• Connor JM, Evans DA. Fibrodysplasia ossificans progressiva. The clinical features and natural history of 34 patients. J Bone Joint Surg Br. 1982;64(1):76-83. doi: 10.1302/0301-620X.64B1.7068725.

  PMID: 7068725 BACKGROUND

• Zhang W, Zhang K, Song L, Pang J, Ma H, Shore EM, Kaplan FS, Wang P. The phenotype and genotype of fibrodysplasia ossificans progressiva in China: a report of 72 cases. Bone. 2013 Dec;57(2):386-91. doi: 10.1016/j.bone.2013.09.002. Epub 2013 Sep 17.

  PMID: 24051199 BACKGROUND

• Cohen RB, Hahn GV, Tabas JA, Peeper J, Levitz CL, Sando A, Sando N, Zasloff M, Kaplan FS. The natural history of heterotopic ossification in patients who have fibrodysplasia ossificans progressiva. A study of forty-four patients. J Bone Joint Surg Am. 1993 Feb;75(2):215-9. doi: 10.2106/00004623-199302000-00008.

  PMID: 8423182 BACKGROUND

• Kaplan FS, Sponseller PD, Pignolo RJ. Thoracic Deformity in Fibrodysplasia Ossificans Progressiva. JBJS Rev. 2025 May 22;13(5). doi: 10.2106/JBJS.RVW.25.00042. eCollection 2025 May 1.

  PMID: 40403126 DERIVED

• Pignolo RJ, Al Mukaddam M, Baujat G, Brown MA, De Cunto C, Hsiao EC, Keen R, Le Quan Sang KH, Grogan DR, Marino R, Strahs AR, Kaplan FS. Study methodology and insights from the palovarotene clinical development program in fibrodysplasia ossificans progressiva. BMC Med Res Methodol. 2023 Nov 13;23(1):269. doi: 10.1186/s12874-023-02080-7.

  PMID: 37957586 DERIVED

• Pignolo RJ, Hsiao EC, Al Mukaddam M, Baujat G, Berglund SK, Brown MA, Cheung AM, De Cunto C, Delai P, Haga N, Kannu P, Keen R, Le Quan Sang KH, Mancilla EE, Marino R, Strahs A, Kaplan FS. Reduction of New Heterotopic Ossification (HO) in the Open-Label, Phase 3 MOVE Trial of Palovarotene for Fibrodysplasia Ossificans Progressiva (FOP). J Bone Miner Res. 2023 Mar;38(3):381-394. doi: 10.1002/jbmr.4762. Epub 2023 Jan 25.

  PMID: 36583535 DERIVED

• Pignolo RJ, Kimel M, Whalen J, Kawata AK, Artyomenko A, Kaplan FS. The Fibrodysplasia Ossificans Progressiva Physical Function Questionnaire (FOP-PFQ): A patient-reported, disease-specific measure. Bone. 2023 Mar;168:116642. doi: 10.1016/j.bone.2022.116642. Epub 2022 Dec 13.

  PMID: 36526263 DERIVED

• Warner SE, Kaplan FS, Pignolo RJ, Smith SE, Hsiao EC, De Cunto C, Di Rocco M, Harnett K, Grogan D, Genant HK. Whole-body Computed Tomography Versus Dual Energy X-ray Absorptiometry for Assessing Heterotopic Ossification in Fibrodysplasia Ossificans Progressiva. Calcif Tissue Int. 2021 Dec;109(6):615-625. doi: 10.1007/s00223-021-00877-6. Epub 2021 Jul 31.

  PMID: 34331548 DERIVED

• Kou S, De Cunto C, Baujat G, Wentworth KL, Grogan DR, Brown MA, Di Rocco M, Keen R, Al Mukaddam M, le Quan Sang KH, Masharani U, Kaplan FS, Pignolo RJ, Hsiao EC. Patients with ACVR1R206H mutations have an increased prevalence of cardiac conduction abnormalities on electrocardiogram in a natural history study of Fibrodysplasia Ossificans Progressiva. Orphanet J Rare Dis. 2020 Jul 29;15(1):193. doi: 10.1186/s13023-020-01465-x.

  PMID: 32727600 DERIVED

• Towler OW, Shore EM, Kaplan FS. Skeletal malformations and developmental arthropathy in individuals who have fibrodysplasia ossificans progressiva. Bone. 2020 Jan;130:115116. doi: 10.1016/j.bone.2019.115116. Epub 2019 Oct 23.

  PMID: 31655222 DERIVED

• Pignolo RJ, Baujat G, Brown MA, De Cunto C, Di Rocco M, Hsiao EC, Keen R, Al Mukaddam M, Sang KLQ, Wilson A, White B, Grogan DR, Kaplan FS. Natural history of fibrodysplasia ossificans progressiva: cross-sectional analysis of annotated baseline phenotypes. Orphanet J Rare Dis. 2019 May 3;14(1):98. doi: 10.1186/s13023-019-1068-7.

  PMID: 31053156 DERIVED

Related Links

• website for the International FOP Association
• Click here for more information about this study: A Natural History, Non-Intervention Study in Subjects with Fibrodysplasia Ossificans Progressiva (FOP)

Biospecimen

Retention: SAMPLES WITH DNA

Blood and urine samples for biomarker and proteomic analysis.

MeSH Terms

Conditions

Myositis Ossificans; Ossification, Heterotopic

Condition Hierarchy (Ancestors)

Myositis; Muscular Diseases; Musculoskeletal Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Ipsen Medical Director

  Ipsen

  STUDY DIRECTOR

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 8, 2014
• First Posted: December 23, 2014
• Study Start: December 18, 2014
• Primary Completion: April 9, 2020
• Study Completion: April 9, 2020
• Last Updated: June 26, 2020

Record last verified: 2020-06

Locations

AR (1); AU (1); FR (1); GB (1); IT (1); US (2)