FOP is caused by a mutation in the ACVR1 gene that encodes for the ACVR1/ALK2 receptor. This receptor is part of the bone morphogenetic protein (BMP) signaling pathway and is critical in the regulation of cartilage and bone development and growth. The mutation leads to increased activity of the ACVR1/ALK2 receptor. The mutated, overactive receptor leads to excess phosphorylation of Smads 1/5/8 and enhanced signals to the nucleus to form heterotopic bone. Palovarotene binds to RARγ which decreases levels of Smad 1/5/8 proteins signaling, repressing excess BMP which may prevent the formation of abnormal new bone.

About the Clinical Trial

The Phase 3 trial is a global, multi-center, open-label (no placebo) trial. Approximately 80 adults and children over 4 years of age with the classic FOP mutation (R206H mutation) will be needed to complete the Phase 3 clinical trial. The trial is designed to evaluate whether a daily dosing regimen of palovarotene, with higher doses during times of flare-ups, will reduce the formation of new HO.

Eligibility Criteria*

• AGE: 4-60
• DISEASE ACTIVITY: No flare symptoms in prior 4 weeks
• MUTATIONS: R206H (non R206H may participate in a sub-study)

Study Design*

• STUDY TYPE:  Interventional
• RANDOMIZED STUDY:  No
• PLACEBO CONTROLLED:  No
• LENGTH OF PARTICIPATION: 24 months
• NUMBER OF STUDY VISITS: 6

Status

Phase 3, Enrolling

Study Sponsor

Clementia Pharmaceuticals

Therapy Approach

Smad inhibitor

Participating Clinical Sites

University of California San Francisco
San Francisco, California, United States, 94143
Contact: Tea Chan
Principal Investigator: Edward Hsiao, MD, PhD

Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104
Contact: Edna Mancilla, MD
Principal Investigator: Edna Mancilla, MD

University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
Contact: Katherine S. Toder, CCRC
Principal Investigator: Mona Al Mukaddam, MD, MS

Toronto General Hospital
Toronto, Ontario, Canada, M5G 2C4
Contact: Irene Ho
Principal Investigator: Angela Cheung, MD, PhD

Groupe Hospitalier Necker Enfants Malades 
Paris, France, 75015
Contact: Genevieve Baujat, MD
Principal Investigator: Genevieve Baujat, MD

Hospital Universitari i Politècnic La Fe
Valencia, Avinguda De Fernando Abril Martorell, Nº 106, Spain, 46026
Contact: Inmaculada Calvo, MD, Ph
Principal Investigator: Inmaculada Calvo, MD, PhD

Norrlands Universitetssjukhus 
Umeå, Sweden, SE-90185
Contact: Staffan Berglund, MD, PhD
Principal Investigator: Staffan Berglund, MD, PhD

Royal National Orthopaedic Hospital, Brockely Hill 
Stanmore, United Kingdom, HA7 4LP
Contact: Richard Keen, MD
Contact: Jackie Vinton
Principal Investigator: Richard Keen, MD