Fibrodysplasia Ossificans Progressiva (FOP)
Conditions
Keywords
heterotopic ossification, canakinumab, anakinra, FOP
Brief 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. 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
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.
Interventions
OTHERAnti-IL1 Therapy
Anti-IL1 is a rescue therapy for FOP patients that is hypothesized to reduce flare activity and subsequent ossification in these patients
Sponsors
University of California, San Francisco
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
6 Years to 30 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of flares that a patient experiences. | 1 year | Surveys will be used to track the number of clinical flares that a patient experiences before and during treatment with anti-IL1 therapy. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in new heterotopic ossification bone formation over time | 1 year | 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. |
| Changes in blood inflammatory cytokine levels with anti-IL1 therapy | 1 year | 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. |
| Change in patient mobility | 1 year | 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. |
| Number of participants with treatment emergent adverse events (TEAEs) | 1 year | The number of participants with adverse events (ie adverse events not at baseline) will be collected during the treatment period. |
Countries
United States
Contacts
CONTACTSamantha Klein
CONTACTJudy Gonzalez-Vargas
PRINCIPAL_INVESTIGATOREdward Hsiao, MD, PhD
University of California, San Francisco
Outcome results
None listed