A Natural History Study of Fibrodysplasia Ossificans Progressiva (FOP)

NCT ID: NCT02322255

Last Updated: 2020-06-26

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

114 participants

Study Classification

OBSERVATIONAL

Study Start Date

2014-12-18

Study Completion Date

2020-04-09

Brief Summary

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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.

Detailed Description

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This is a multi-center, natural history, non-interventional, longitudinal study in subjects with classic FOP. A thorough baseline examination will be performed to determine the current status of disease in each subject. In Part A, two imaging modalities assessed total body HO at baseline, and the optimal method (low-dose whole body CT scan \[excluding head\]) will be employed in Part B for the balance of the study. Progression will be assessed at annual in-clinic visits (ie, at Months 12, 24, and 36) at which time the procedures conducted at the baseline visit will be repeated. In addition, site personnel will telephone subjects midway between the annual visits (ie, at Months 6, 18, and 30).

During the 36-month follow-up period, at least one new flare-up (with a maximum of one per year) will be carefully studied. An in-clinic visit will be performed within 14 days following the subject's identification of his/her flare-up. Additional visits at Day 42 and Day 84 (after the initial flare-up clinic visit) will be performed. An additional future visit may be scheduled after Day 84 at the discretion of the Principal Investigator (PI) for prolonged flare-ups. However, subjects with an eligible flare-up may elect to participate in an ongoing Clementia interventional study rather than continue in this natural history study.

Conditions

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Fibrodysplasia Ossificans Progressiva

Study Design

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Observational Model Type

CASE_ONLY

Study Time Perspective

PROSPECTIVE

Study Groups

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All Subjects

All subjects enrolled in the study.

No interventions assigned to this group

Eligibility Criteria

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Inclusion Criteria

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

Exclusion Criteria

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

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Clementia Pharmaceuticals Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Ipsen Medical Director

Role: STUDY_DIRECTOR

Ipsen

Locations

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University of California San Francisco, Division of Endocrinology and Metabolism

San Francisco, California, United States

Site Status

University of Pennsylvania, Center for FOP & Related Bone Disorders

Philadelphia, Pennsylvania, United States

Site Status

Hospital Italiano de Buenos Aires, Department of Pediatrics

Buenos Aires, , Argentina

Site Status

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

Woolloongabba, Queensland, Australia

Site Status

Hôpital Necker-Enfants Malades, Department of Genetics

Paris, , France

Site Status

Gaslini Institute, Unit of Rare Diseases, Department of Pediatrics

Genoa, , Italy

Site Status

The Royal National Orthopaedic Hospital, Brockley Hill

Stanmore, Middlesex, United Kingdom

Site Status

Countries

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United States Argentina Australia France Italy United Kingdom

References

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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.

Reference Type DERIVED
PMID: 40403126 (View on PubMed)

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.

Reference Type DERIVED
PMID: 37957586 (View on PubMed)

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.

Reference Type DERIVED
PMID: 36583535 (View on PubMed)

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.

Reference Type DERIVED
PMID: 36526263 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 7068725 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24051199 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 8423182 (View on PubMed)

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.

Reference Type DERIVED
PMID: 34331548 (View on PubMed)

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.

Reference Type DERIVED
PMID: 32727600 (View on PubMed)

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.

Reference Type DERIVED
PMID: 31655222 (View on PubMed)

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.

Reference Type DERIVED
PMID: 31053156 (View on PubMed)

Related Links

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http://www.ifopa.org

website for the International FOP Association

http://clementiapharma.com/

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

Other Identifiers

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PVO-1A-001

Identifier Type: -

Identifier Source: org_study_id

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