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.
Update as of August 16, 2023: Palovarotene (now known as SohonosTM) has been approved for the treatment of FOP in females aged 8 and over and males aged 10 and over in Canada and the United States. Palovarotene has also received provisional approval in the United Arab Emirates.
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: Studies that assess safety and effectiveness of the drug in a larger group of patients. The drug is typically compared to a standard treatment(s) or to no treatment (e.g. natural history study or a placebo).
4 to less than 14—Phase 3, On Hold, enrollment complete
Study Sponsor
Ipsen
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 [email protected]
Principal Investigator: Edward Hsiao, MD, PhD
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104
Contact: Edna Mancilla, MD [email protected]
Principal Investigator: Edna Mancilla, MD
University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
Contact: Katherine S. Toder, CCRC [email protected]
Principal Investigator: Mona Al Mukaddam, MD, MS
Mayo Clinic
Rochester, Minnesota, United States, 55905
Contact: Nicole Bernal [email protected]
Principal Investigator: Robert J Pignolo, MD, PhD
Toronto General Hospital
Toronto, Ontario, Canada, M5G 2C4
Contact: Irene Ho [email protected]
Principal Investigator: Angela Cheung, MD, PhD
Hospital for Sick Children
Toronto, Ontario, Canada, M5G 1X8
Contact: Peter Kannu, MB ChB (Otago), PhD, DCH [email protected]
Principal Investigator: Peter Kannu, MB ChB (Otago), PhD, DCH
Groupe Hospitalier Necker Enfants Malades
Paris, France, 75015
Contact: Genevieve Baujat, MD [email protected]
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 [email protected]
Principal Investigator: Inmaculada Calvo, MD, PhD
Norrlands Universitetssjukhus
Umeå, Sweden, SE-90185
Contact: Staffan Berglund, MD, PhD [email protected]
Principal Investigator: Staffan Berglund, MD, PhD
Royal National Orthopaedic Hospital, Brockely Hill
Stanmore, United Kingdom, HA7 4LP
Contact: Richard Keen, MD [email protected]
Contact: Jackie Vinton [email protected]
Principal Investigator: Richard Keen, MD
Istituto Giannina, Department of Pediatrics
Genova, Liguria, Italy, 16148
Contact: Maja Di Rocco, MD [email protected]
Principal Investigator: Maja Di Rocco, MD
Hospital Italiano de Buenos Aires
Buenos Aires, Argentina, C1199ABB
Contact: Carmen Laura De Cunto, [email protected]
Principal Investigator: Carmen Laura De Cunto, MD
Queensland University of Technology
Woolloongabba, Queensland, Australia, 4102
Contact: Matthew Brown, MD [email protected]
Principal Investigator: Matthew Brown, MD
Hospital Israelita Albert Einstein
Sao Paulo, SP, Brazil, 05652-900
Contact: Patricia Longo Ribeiro Delai, [email protected]
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
Speak with your physician if you have any questions about the palovarotene clinical trials.
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.
