An Observational Pre-post Study to Observe if the Off Label Use of Anti-IL1 Therapies, Such as Anakinra or Canakinumab, Can Block ACVR1-induced Flare Activity and Heterotopic Ossification in FOP

NCT ID: NCT06724562

Last Updated: 2025-12-30

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

RECRUITING

Total Enrollment

11 participants

Study Classification

OBSERVATIONAL

Study Start Date

2025-04-01

Study Completion Date

2027-03-31

Brief Summary

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This is an observational pre-post study to observe if the off label use of anti-IL1 therapies, such as anakinra or canakinumab, can block ACVR1-induced flare activity and heterotopic ossification in FOP. It will also generate key tools and preliminary data that are needed to design a future Phase II study.

This study specifically focuses on patients with severe FOP who are being considered by their medical team for rescue therapy with anti-IL1 therapy. Preliminary data suggests patients experience significant decreases in flare frequency when taking anti-IL1 therapy, but other measures of efficacy remain unassessed, such as changes in heterotopic ossification formation, changes in pain medication use, and changes in functionality.

Detailed Description

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The investigators will perform an observational study on patients with FOP who have decided, along with their primary medical team, to start anti-IL1 therapy with either anakinra or canakinumab due to intractable or unusually severe FOP disease progression. The investigators will study 11 subjects aged 6-30 years old, with a self-reported flare frequency of at least 4 flares/year \[2 times above the average reported FOP population flare frequency of 2 flares/year\] or with an intractable flare that has lasted greater than 1 month. Subjects will begin an observational period during the medication prescription and insurance approval process and will then be followed for up to 1 year after treatment has been initiated by the medical management team. Low-dose whole-body CT (WBCT) imaging, bloodwork, patient-reported outcomes, pain, and flare activity will be assessed during this study. In addition, patients who are currently on anti-IL1 therapy will be enrolled in a separate observation-only arm to collect historical data related to their experiences on therapy.

Conditions

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Fibrodysplasia Ossificans Progressiva (FOP)

Keywords

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heterotopic ossification canakinumab anakinra FOP

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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Anti-IL1 Observational Arm

FOP patients that are beginning treatment with Anti-IL1 Therapy

Anti-IL1 Therapy

Intervention Type OTHER

Anti-IL1 is a rescue therapy for FOP patients that is hypothesized to reduce flare activity and subsequent ossification in these patients

Optional Non-Treatment Observational Arm

FOP patients unable to obtain Anti-IL1 therapy

No interventions assigned to this group

"On Treatment" Observational Arm

FOP patients that are already using Anti-IL1 therapy

No interventions assigned to this group

Interventions

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Anti-IL1 Therapy

Anti-IL1 is a rescue therapy for FOP patients that is hypothesized to reduce flare activity and subsequent ossification in these patients

Intervention Type OTHER

Other Intervention Names

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Canakinumab Anakinra

Eligibility Criteria

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Inclusion Criteria

* Patients with a clinical presentation consistent with FOP and a genetic diagnosis of classical FOP (ACVR1R206H variant) (2), male or female aged 6-30 years old.
* Patients with unusually severe FOP disease activity. This will be determined by FOP flare frequency of \>4 flares per year, which is 2 times higher than the reported average in prior FOP studies ; or by a persistent flare that has failed to resolve after 1 month of standard-of-care therapy.
* Patients whose primary medical team has decided that rescue therapy with an anti-IL1 medication should be initiated. Once the primary medical team has decided that anti-IL1 therapy should be pursued, the subject will be told about this clinical-observational study and enrolled in the pre-treatment phase while access to the anti-IL1 therapy is being obtained by the clinical management team.
* Ability to participate in all assessments, including blood draws, radiology assessments, and travel. Age 6 is chosen as the lower limit to avoid the need for anesthesia for whole body CT in younger subjects.
* No history of unexplained infections, known autoimmune disease, or contraindication to anti-IL1 therapy.
* Written informed consent (and assent when applicable) obtained from subject or subject's legal representative and ability for subject to comply with the requirements of the study.

Exclusion Criteria

* Pregnant, breastfeeding, or unwilling to practice birth control during participation in the study.
* Presence of a condition or abnormality that in the opinion of the Investigator would compromise the safety of the patient or the quality of the data.
* Inability to travel to site for assessments
* Pre-existing autoimmune or autoinflammatory disease (aside from FOP)
* Inability to tolerate assessments (such as phlebotomy)
* Unexplained infections
* Current participation in an interventional trial, or study of a potentially disease modifying medication
* Inability to take medications as prescribed by managing physician
Minimum Eligible Age

6 Years

Maximum Eligible Age

30 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

NIH

Sponsor Role collaborator

University of California, San Francisco

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Edward Hsiao, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University of California, San Francisco

Locations

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UCSF

San Francisco, California, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Samantha Klein

Role: CONTACT

Phone: 415-254-5748

Email: [email protected]

Judy Gonzalez-Vargas

Role: CONTACT

Phone: 415-254-5048

Email: [email protected]

Facility Contacts

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Edward Hsiao, MD, PhD

Role: primary

References

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Haviv R, Zeitlin L, Moshe V, Ziv A, Rabinowicz N, De Benedetti F, Prencipe G, Matteo V, De Cunto CL, Hsiao EC, Uziel Y. Long-term use of interleukin-1 inhibitors reduce flare activity in patients with fibrodysplasia ossificans progressiva. Rheumatology (Oxford). 2024 Sep 1;63(9):2597-2604. doi: 10.1093/rheumatology/keae255.

Reference Type BACKGROUND
PMID: 38733591 (View on PubMed)

Haviv R, Moshe V, De Benedetti F, Prencipe G, Rabinowicz N, Uziel Y. Is fibrodysplasia ossificans progressiva an interleukin-1 driven auto-inflammatory syndrome? Pediatr Rheumatol Online J. 2019 Dec 21;17(1):84. doi: 10.1186/s12969-019-0386-6.

Reference Type BACKGROUND
PMID: 31864380 (View on PubMed)

Other Identifiers

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R01AR083628

Identifier Type: NIH

Identifier Source: secondary_id

View Link

23-40055

Identifier Type: -

Identifier Source: org_study_id