IL1 Inhibition in FOP

NCT06724562 | Recruiting

• 2 other identifiers: 23-40055R01AR083628
• Study Type: observational
• Target: 11
• Locations: 1 country
• Sites: 1

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.

Conditions

Fibrodysplasia Ossificans Progressiva (FOP)

Keywords

heterotopic ossification; canakinumab; anakinra; FOP

Outcome Measures

Primary Outcomes (1)

• 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.

  1 year

Secondary Outcomes (4)

• Change in new heterotopic ossification bone formation over time

  1 year

• Changes in blood inflammatory cytokine levels with anti-IL1 therapy

  1 year

• Change in patient mobility

  1 year

• Number of participants with treatment emergent adverse events (TEAEs)

  1 year

Study Arms (3)

Anti-IL1 Observational Arm

FOP patients that are beginning treatment with Anti-IL1 Therapy

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

Interventions

Anti-IL1 Therapy OTHER

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

Also known as: Canakinumab, Anakinra

Anti-IL1 Observational Arm

Eligibility Criteria

• Age: 6 Years - 30 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Subjects with a diagnosis of FOP who meet the inclusion and exclusion criteria will be eligible for participation in this study.

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS): collaborator
• University of California, San Francisco: lead

Study Sites (1)

UCSF

San Francisco, California, 94143, United States

RECRUITING

Related Publications (2)

• 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.

  PMID: 38733591 BACKGROUND

• 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.

  PMID: 31864380 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Blood samples for DNA, cell isolation, biochemistry, and cytokine analyses.

MeSH Terms

Conditions

Myositis Ossificans; Ossification, Heterotopic

Interventions

canakinumab; Interleukin 1 Receptor Antagonist Protein

Condition Hierarchy (Ancestors)

Myositis; Muscular Diseases; Musculoskeletal Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Study Officials

• Edward Hsiao, MD, PhD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Samantha Klein

CONTACT

415-254-5748; Samantha.klein@ucsf.edu

Judy Gonzalez-Vargas

CONTACT

415-254-5048; Judy.Gonzalez-Vargas@ucsf.edu

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 27, 2024
• First Posted: December 9, 2024
• Study Start: April 1, 2025
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): March 1, 2027
• Last Updated: March 3, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: Within 2 years of the end of the study.

Locations

US (1)