Fibrodysplasia Ossificans Progressiva (FOP)NCT06724562
IL1 Inhibition in FOP
An observational study of Fibrodysplasia Ossificans Progressiva (FOP), run by University of California, San Francisco at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 6 to 30 years
- Conditions the study is for
- Fibrodysplasia Ossificans Progressiva (FOP)
- What is being tested?
- Anti-IL1 Therapy
- How many people
- 11 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Apr 2025to 5 Nov 2027
- 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 6 to 30 years
- All sexes
- No healthy volunteers
- Child, Adult
Study population: Subjects with a diagnosis of FOP who meet the inclusion and exclusion criteria will be eligible for participation in this study.
Who may be able to join
- 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.
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
UCSF
San Francisco, California, 94143
Edward Hsiao, MD, PhD, 415-476-9732, edward.hsiao@ucsf.edu
About this study
Official title: An Observational Study of IL1 Inhibition for Blocking ACVR1-Induced Flare Activity and Heterotopic Ossification in Fibrodysplasia Ossificans Progressiva (FOP)
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.
Read the detailed description
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, or are unable to attain anti-IL1 therapy, will be enrolled in a separate observation-only arm to collect historical data related to their experiences on therapy.
- Being tested
- Anti-IL1 Therapy
- Keywords
- heterotopic ossification, canakinumab, anakinra, FOP
- 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.
Anti-IL1 TherapyOther
Also called Canakinumab, Anakinra
Anti-IL1 is a rescue therapy for FOP patients that is hypothesized to reduce flare activity and subsequent ossification in these patients
| Study group | Role | What they receive |
|---|---|---|
| Anti-IL1 Observational Arm | FOP patients that are beginning treatment with Anti-IL1 Therapy Receives: Other: Anti-IL1 Therapy | |
| Optional Non-Treatment Observational Arm | FOP patients unable to obtain Anti-IL1 therapy | |
| "On Treatment" Observational Arm | FOP patients that are already using Anti-IL1 therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of flares that a patient experiences.
Surveys will be used to track the number of clinical flares that a patient experiences before and during treatment with anti-IL1 therapy.
Measured: 1 year
Secondary outcomes (4)
Change in new heterotopic ossification bone formation over time
Low dose whole body CT (WBCT) without the head, will be used to create detailed images of the skeletal system. The images will be used to measure new HO bone formation from baseline.
Measured: 1 year
Changes in blood inflammatory cytokine levels with anti-IL1 therapy
Blood samples will be taken to measure changes in the inflammatory cytokines present in the blood over time, and if this changes with anti-IL1 treatment.
Measured: 1 year
Change in patient mobility
The Cumulative Analog Joint Involvement Scale (CAJIS) will be used to assess 15 major joints for their mobility. This will be compared from baseline vs. 1 year of anti-IL1 treatment.
Measured: 1 year
Number of participants with treatment emergent adverse events (TEAEs)
The number of participants with adverse events (ie adverse events not at baseline) will be collected during the treatment period.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Dec 2024
- Study start1 Apr 2025
- Primary completion5 Nov 2027 (estimated)
- Study completion5 Nov 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Fibrodysplasia Ossificans Progressiva (FOP)Studies of the same condition, open and under way.
- More trials run by University of California, San FranciscoThe sponsor's other registered studies.
- 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
- Cohort
- Time perspective
- Prospective
- Enrolment
- 11 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of California, San Francisco
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
- Responsible party
- Sponsor
- Investigators
- Edward Hsiao, MD, PhD, Principal investigator, University of California, San Francisco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06724562
- Sponsor's protocol ID
- 23-40055
- Other IDs
- R01AR083628
- Status last verified
- Aug 2026
- First submitted
- 27 Nov 2024
- Last updated
- 6 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Patient data will be deidentified and shared following NIH policies for aggregate and individual level data.
Publications
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.
PubMed 38733591Haviv 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.
PubMed 31864380