PROGRESS Trial (zilurgisertib)

PROGRESS Trial (zilurgisertib)

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 Icon
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 Icon
Study Design*
  • STUDY TYPE:  Interventional
  • 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 Icon

Phase 2, Active, Enrolling

Therapy Approach Icon

Therapy Approach

Kinase Inhibitor

Study Sponsor Icon

Study Sponsor

Incyte Corporation

*For the complete list of eligibility criteria and details on this study, visit and enter Identifier NCT05090891.

Participating Clinical Sites (as of March 1, 2024)

Murdoch Children's Research Institute
Principal Investigator: Dr. Ravi Savarirayan

Royal North Shore Hospital 
Principal Investigator: Roderick Clifton-Bligh, BSC MB FRACP PhD FFSc

Albert Einstein Israelite Hospital
Principal Investigator: Patricia Delai, MD

University Health Network - Toronto General Hospital
Principal Investigator: Angela Cheung, MD, PhD

Centro de Estudios Reumatológicos
Principal Investigator: Dr. Mabel Ladino

Tongji University – Tongji Hospital 
Principal Investigator: 
Keqin Zhang, MD, PhD

Beijing Children's Hospital
Principal Investigator: Caifeng Li, MD

Shanghai Children's Medical Center
Principal Investigator: Dr. Xiumin Wang

Children's Hospital of Fudan University
Principal Investigator: Dr. Li Sun

Groupe Hospitalier Necker Enfants Malades
Principal Investigator: Dr. Genevieve Baujat

AP-HP Hôpital Lariboisière
Principal Investigator: Thomas Funck-Brentano, MD, PhD

Universitätsklinikum Köln
Principal Investigator: Dr. Heike Hoyer-Kuhn

Instituto Nacional De Rehabilitacion Luis Guillermo Ibarra
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
Principal Investigator: Dr. Francisco Javier Bachiller-Corral

Royal National Orthopaedic Hospital
Principal Investigator: Dr. Richard Keen

The Perelman School of Medicine – The University of Pennsylvania
Principal Investigator: Mona Al Mukaddam, MS, MD

Children’s Hospital of Philadelphia
Principal Investigator: Edna Mancilla, MD

Mayo Clinic
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.

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