FOP is caused by a mutation in the ACVR1 gene that results in excessive bone morphogenetic protein (BMP) signaling, which regulates cartilage and bone development. The FOP mutation increases BMP signaling, resulting in the formation of heterotopic bone. By reducing BMP signaling, palovarotene may reduce the volume of heterotopic bone formed in FOP patients. Palovarotene has received Orphan Drug status for FOP from the U.S. Food and Drug Administration (FDA), and orphan status for the treatment of FOP in the EU. In addition, palovarotene has been granted Fast Track and Breakthrough Therapy designations for FOP from the FDA.

About the Clinical Trial

The palovarotene Phase 3 trial is a global, multi-center, open-label (no placebo – see below study design) single-treatment arm trial in which all subjects receive palovarotene dosing. The study was designed to enroll approximately 80 adults and children age 4 years and older with the classic FOP mutation (R206H mutation). Key objectives are to evaluate the safety of palovarotene, and whether a daily dosing regimen of the drug, with higher doses during times of flare-ups, will reduce the formation of new HO as measured by whole body CT scan.

Eligibility Criteria*

• AGE: 4 years old and above
• DISEASE ACTIVITY: No flare-up symptoms in prior 4 weeks
• MUTATIONS: R206H

Study Design*

• STUDY TYPE: Interventional
• RANDOMIZED STUDY: No, single-treatment arm study
• PLACEBO CONTROLLED: No, the control group is the Clementia Natural History Study
• LENGTH OF PARTICIPATION: 24 months
• NUMBER OF STUDY VISITS: 5 (in clinic) with remote visits for safety monitoring

Status

Phase 3, Active, enrollment complete

Study Sponsor

Clementia, an Ipsen Company

Therapy Approach

Inhibition of downstream ACVR1 receptor signaling through Smad phosphorylation inhibition and degradation

*For the complete list of eligibility criteria and details on this study, visit ClinicalTrials.gov and use NCT03312634.

Participating Clinical Sites

(All active but no longer recruiting)

University of California San Francisco
San Francisco, California, United States, 94143
Contact: Tea Chan tea.chan@ucsf.edu
Principal Investigator: Edward Hsiao, MD, PhD

Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104
Contact: Edna Mancilla, MD mancillae@email.chop.edu
Principal Investigator: Edna Mancilla, MD

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

Mayo Clinic
Rochester, Minnesota, United States, 55905
Contact: Nicole Bernal bernal.nicole@mayo.edu
Principal Investigator: Robert J Pignolo, MD, PhD

Toronto General Hospital
Toronto, Ontario, Canada, M5G 2C4
Contact: Irene Ho irene.ho@uhn.ca
Principal Investigator: Angela Cheung, MD, PhD

Hospital for Sick Children
Toronto, Ontario, Canada, M5G 1X8
Contact: Peter Kannu, MB ChB (Otago), PhD, DCH peter.kannu@sickkids.ca
Principal Investigator: Peter Kannu, MB ChB (Otago), PhD, DCH

Groupe Hospitalier Necker Enfants Malades
Paris, France, 75015
Contact: Genevieve Baujat, MD genevieve.baujat@aphp.fr
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, PhD calvo_inm@gva.es
Principal Investigator: Inmaculada Calvo, MD, PhD

Norrlands Universitetssjukhus
Umeå, Sweden, SE-90185
Contact: Staffan Berglund, MD, PhD staffan.berglund@umu.se
Principal Investigator: Staffan Berglund, MD, PhD

Royal National Orthopaedic Hospital, Brockely Hill
Stanmore, United Kingdom, HA7 4LP
Contact: Richard Keen, MD richard.keen1@nhs.net
Contact: Jackie Vinton jvinton@nhs.net
Principal Investigator: Richard Keen, MD

Istituto Giannina, Department of Pediatrics
Genova, Liguria, Italy, 16148
Contact: Maja Di Rocco, MD majadirocco@gaslini.org
Principal Investigator: Maja Di Rocco, MD

Hospital Italiano de Buenos Aires
Buenos Aires, Argentina, C1199ABB
Contact: Carmen Laura De Cunto, carmen.decunto@hospitalitaliano.org.ar
Principal Investigator: Carmen Laura De Cunto, MD

Queensland University of Technology
Woolloongabba, Queensland, Australia, 4102
Contact: Matthew Brown, MD matt.brown@qut.edu.au
Principal Investigator: Matthew Brown, MD

Hospital Israelita Albert Einstein
Sao Paulo, SP, Brazil, 05652-900
Contact: Patricia Longo Ribeiro Delai, pdelai@pvo-trials.com
Principal Investigator: Patricia Longo Ribeiro Delai, MD

The University of Tokyo Hospital
Tokyo, Bunkyo-ku, Japan, 113-8655
Contact: Nobuhiko Haga, MD +81 3 3815 5411
Principal Investigator: Nobuhiko Haga, MD

For additional information on palovarotene drug development program, have your doctor contact Clementia clinical trial resource line or email address:
1-800-750-8710
ClinicalTrials@clementiapharma.com