FOP patients harbor mutations in the ALK2 protein (also known as ACVR1) that drives excessive bone morphogenetic protein (BMP) signaling, which regulates cartilage and bone development.
Zilurgisertib (INCB000928) is an oral investigational drug designed to target and block this disease-causing mutant FOP protein hyperactivity. In preclinical studies, zilurgisertib demonstrated potency for the target kinase, selectivity, safety and strong suppression of heterotopic ossification (HO) in animal models.
About the Clinical Trial
The PROGRESS Phase 2 trial is a global, multi-center, placebo-controlled trial. Approximately 60 patients 12 years of age or older with the R206H ACVR1 mutation or other FOP variants associated with progressive HO will be enrolled. The trial is designed to evaluate the efficacy, safety and tolerability of zilurgisertib compared with placebo. Total volume of new HO will be evaluated along with the number of new flares, flare-related symptoms and treatment emergent adverse events.
Eligibility Criteria*
- AGE: ≥ 12
- DISEASE ACTIVITY: Signs and symptoms associated with FOP flare-ups, worsening of joint function, or new heterotopic ossification (HO)
- MUTATIONS: R206H and other mutations of the ACVR1 gene resulting in HO
Study Design*
- STUDY TYPE: Interventional
- RANDOMIZED STUDY: Yes
- PLACEBO CONTROLLED: Yes, participants will be randomized to zilurgisertib or placebo
- LENGTH OF PARTICIPATION: 24 week (double-blind portion); 52 week (open-label portion)
- NUMBER OF STUDY VISITS: 9 onsite and 15 remote
Status
Phase 2, Active, Enrolling
Therapy Approach
Kinase Inhibitor
Study Sponsor
Incyte Corporation
*For the complete list of eligibility criteria and details on this study, visit ClinicalTrials.gov and enter Identifier NCT05090891.
Participating Clinical Sites (as of March 1, 2024)
Murdoch Children's Research Institute
Australia
Principal Investigator: Dr. Ravi Savarirayan
Royal North Shore Hospital
Australia
Principal Investigator: Roderick Clifton-Bligh, BSC MB FRACP PhD FFSc
Albert Einstein Israelite Hospital
Brazil
Principal Investigator: Patricia Delai, MD
University Health Network - Toronto General Hospital
Canada
Principal Investigator: Angela Cheung, MD, PhD
Centro de Estudios Reumatológicos
Chile
Principal Investigator: Dr. Mabel Ladino
Tongji University – Tongji Hospital
China
Principal Investigator: Keqin Zhang, MD, PhD
Beijing Children's Hospital
China
Principal Investigator: Caifeng Li, MD
Shanghai Children's Medical Center
China
Principal Investigator: Dr. Xiumin Wang
Children's Hospital of Fudan University
China
Principal Investigator: Dr. Li Sun
Groupe Hospitalier Necker Enfants Malades
France
Principal Investigator: Dr. Genevieve Baujat
AP-HP Hôpital Lariboisière
France
Principal Investigator: Thomas Funck-Brentano, MD, PhD
Universitätsklinikum Köln
Germany
Principal Investigator: Dr. Heike Hoyer-Kuhn
Instituto Nacional De Rehabilitacion Luis Guillermo Ibarra
Mexico
Principal Investigator: Alberto Hidalgo Bravo, PhD
Groote Schuur Hospital
South Africa
Principal Investigator: Dr. Raphaella Stander
Seoul National University Hospital
South Korea
Principal Investigator: Tae-Joon Cho, MD, PhD
Hospital Universitario Ramon Y Cajal
Spain
Principal Investigator: Dr. Francisco Javier Bachiller-Corral
Royal National Orthopaedic Hospital
UK
Principal Investigator: Dr. Richard Keen
The Perelman School of Medicine – The University of Pennsylvania
USA
Principal Investigator: Mona Al Mukaddam, MS, MD
Children’s Hospital of Philadelphia
USA
Principal Investigator: Edna Mancilla, MD
Mayo Clinic
USA
Principal Investigator: Robert Pignolo, MD, PhD
The IFOPA does not endorse nor recommend specific clinical trials. Please speak with your doctor if you are interested in participating in a clinical trial.
