Fibrodysplasia Ossificans ProgressivaNCT02322255
A Natural History Study of Fibrodysplasia Ossificans Progressiva (FOP)
An observational study of Fibrodysplasia Ossificans Progressiva, run by Clementia Pharmaceuticals Inc. at 7 sites in 6 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages Up to 65 years
- Conditions the study is for
- Fibrodysplasia Ossificans Progressiva
- How many people
- 114 participants
- Where
- 7 sitesin 6 countries
- Study dates
- 18 Dec 2014to 9 Apr 2020
- Phase
- Observational
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 65 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: Individuals with classic FOP (R206H mutation).
Who may be able to join
- Subjects clinically diagnosed with classical FOP with documented R206H mutation or believed to carry the R206H mutation
Who cannot join
- Participation in an interventional clinical research study within the 4 weeks prior to enrollment
Trial locations and contacts
7 sites in 6 countries.
7 sites in 6 countries
United States2 sites
University of Pennsylvania, Center for FOP & Related Bone Disorders
Philadelphia, Pennsylvania, 19104
University of California San Francisco, Division of Endocrinology and Metabolism
San Francisco, California, 94143
Argentina1 site
Hospital Italiano de Buenos Aires, Department of Pediatrics
Buenos Aires
Australia1 site
Queensland University of Technology (QUT) Institute of Health and Biomedical Innovation (IHBI)
Woolloongabba, Queensland, 4102
Italy1 site
Gaslini Institute, Unit of Rare Diseases, Department of Pediatrics
Genoa
United Kingdom1 site
The Royal National Orthopaedic Hospital, Brockley Hill
Stanmore, Middlesex, HA7 4LP
About this study
Official title: A Natural History, Non-Interventional, Two-Part Study in Subjects With Fibrodysplasia Ossificans Progressiva (FOP)
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.
Read the detailed description
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
- 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
- Medical subject headings
- Myositis Ossificans, Ossification, Heterotopic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| All Subjects | All subjects enrolled in the study. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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]).
Measured: Month 36
Secondary outcomes (11)
Change from baseline in physical function as assessed by range of motion.
Measured: Month 12, Month 24, and Month 36
Change from baseline in patient-reported use of assistive devices and adaptations.
Measured: 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]).
Measured: 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).
Measured: Month 6, Month 12, Month 18, Month 24, Month 30, and Month 36
Change from baseline in biomarkers.
Measured: Month 12, Month 24, and Month 36
Flare-up progression as assessed by the change from baseline in heterotopic ossification at the flare-up site.
Measured: Flare-up initiation, Flare-up Days 42 and 84
Flare-up progression as assessed by the change from baseline in pain and swelling at the flare-up site.
Measured: Flare-up initiation, Flare-up Days 42 and 84
Flare-up progression as assessed by the change from baseline biomarkers.
Measured: Flare-up initiation, Flare-up Days 42 and 84
Flare-up progression as assessed by the change from baseline in physical function as assessed by range of motion.
Measured: Flare-up initiation, Flare-up Days 42 and 84
Flare-up progression as assessed by the change from baseline in a disease-specific patient-reported outcome measure (FOP-Physical Function Questionnaire [FOP-PFQ]).
Measured: Flare-up initiation, Flare-up Days 42 and 84
Flare-up progression as assessed by the change from baseline in a patient-reported outcome measure of physical and mental health (PROMIS Global Health Scale).
Measured: Flare-up initiation, Flare-up Days 42 and 84
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Dec 2014 (estimated)
- Study start18 Dec 2014
- Primary completion9 Apr 2020
- Study completion9 Apr 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (12)Papers the sponsor has linked to this study.
- Other trials for Fibrodysplasia Ossificans ProgressivaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case only
- Time perspective
- Prospective
- Enrolment
- 114 participants (actual)
Sponsor and investigators
- Lead sponsor
- Clementia Pharmaceuticals Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Ipsen Medical Director, Study director, Ipsen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02322255
- Sponsor's protocol ID
- PVO-1A-001
- Status last verified
- Jun 2020
- First submitted
- 8 Dec 2014
- Last updated
- 26 Jun 2020
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 7068725Zhang 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.
PubMed 24051199Cohen 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.
PubMed 8423182Pignolo RJ, Hsiao EC, Al Mukaddam M, Baujat G, Berglund SK, Cheung AM, De Cunto C, Delai P, Haga N, Kannu P, Mancilla EE, Marino R, Shih F, Strahs A, Kaplan FS. Palovarotene impact on fibrodysplasia ossificans progressiva (FOP): data from month 48 of the phase III MOVE trial. JBMR Plus. 2026 Aug 29;10(10):ziag141. doi: 10.1093/jbmrpl/ziag141. eCollection 2026 Oct.
PubMed 42770123Kaplan 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.
PubMed 40403126Pignolo 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.
PubMed 37957586Pignolo 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.
PubMed 36583535Pignolo 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.
PubMed 36526263Warner 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.
PubMed 34331548Kou 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.
PubMed 32727600Towler 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.
PubMed 31655222Pignolo 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.
PubMed 31053156