Special considerations for clinical trials in fibrodysplasia ossificans progressiva (FOP)

Edward C Hsiao; Maja Di Rocco; Amanda Cali; Michael Zasloff; Mona Al Mukaddam; Robert J Pignolo; Zvi Grunwald; Coen Netelenbos; Richard Keen; Genevieve Baujat; Matthew A Brown; Tae-Joon Cho; Carmen De Cunto; Patricia Delai; Nobuhiko Haga; Rolf Morhart; Christiaan Scott; Keqin Zhang; Robert J Diecidue; Clive S Friedman; Fredrick S Kaplan; Elisabeth M W Eekhoff

doi:10.1111/bcp.13777

Special considerations for clinical trials in fibrodysplasia ossificans progressiva (FOP)

Br J Clin Pharmacol. 2019 Jun;85(6):1199-1207. doi: 10.1111/bcp.13777. Epub 2018 Nov 6.

Authors

Edward C Hsiao¹, Maja Di Rocco², Amanda Cali³, Michael Zasloff⁴, Mona Al Mukaddam⁵, Robert J Pignolo⁶, Zvi Grunwald⁷, Coen Netelenbos⁸, Richard Keen⁹, Genevieve Baujat¹⁰, Matthew A Brown¹¹, Tae-Joon Cho¹², Carmen De Cunto¹³, Patricia Delai¹⁴, Nobuhiko Haga¹⁵, Rolf Morhart¹⁶, Christiaan Scott¹⁷, Keqin Zhang¹⁸, Robert J Diecidue¹⁹, Clive S Friedman²⁰, Fredrick S Kaplan²¹, Elisabeth M W Eekhoff⁸

Affiliations

¹ Division of Endocrinology and Metabolism, and the Institute for Human Genetics, Department of Medicine, University of California, San Francisco, CA, USA.
² Unit of Rare Diseases, Department of Pediatrics, IRCCS Giannina Gaslini Institute, Genoa, Italy.
³ Radiant Hope Foundation and the Ian Cali FOP Research Fund, PENN Medicine, Center for Research in FOP & Related Disorders.
⁴ Departments of Orthopaedic Surgery and Genetics, The Center for Research in FOP & Related Disorders, University of Pennsylvania School of Medicine; and MedStar Georgetown Transplant Institute Georgetown University School of Medicine, Washington, DC, USA.
⁵ Division of Endocrinology, Diabetes and Metabolism, Departments of Medicine and Orthopaedic Surgery, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
⁶ Department of Medicine, Mayo Clinic, Rochester, MN, USA.
⁷ Department of Anesthesiology, Thomas Jefferson University, Philadelphia, PA, USA.
⁸ Department of Internal Medicine section Endocrinology, Amsterdam Bone Center, Amsterdam University Medical Centers location VUmc, Amsterdam, the Netherlands.
⁹ Royal National Orthopaedic Hospital, Stanmore, UK.
¹⁰ Centre de Référence Maladies Osseuses Constitutionnelles, Departement de Génétique, Hôpital Necker-Enfants Malades, Institut Imagine, Paris, France.
¹¹ Institute of Health and Biomedical Innovation, Queensland University of Technology, Translational Research Institute, Woolloongabba, QLD, Australia.
¹² Division of Pediatric Orthopaedics, Seoul National University Children's Hospital, Seoul, South Korea.
¹³ Pediatric Rheumatology Section, Department of Pediatrics, Hospital Italiano de Buenos Aires, Ciudad Autónoma de Buenos Aires, Argentina.
¹⁴ Hospital Israelita Albert Einstein, Instituto de Ensino e Pesquisa, São Paulo-SP, Brazil.
¹⁵ Department of Rehabilitation Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
¹⁶ Department of Pediatrics, Klinikum Garmisch-Partenkirchen GmbH, Garmisch-Partenkirchen, Germany.
¹⁷ Paediatric Rheumatology, Red Cross Children's Hospital, University of Cape Town, Cape Town, South Africa.
¹⁸ Department of Endocrinology, Tongji Hospital, Shanghai Tongji University, Shanghai, China.
¹⁹ Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, USA.
²⁰ Schulich School of Medicine and Dentistry, Pediatric Oral Health and Dentistry, London, ON, Canada.
²¹ Departments of Medicine & Orthopaedic Surgery, Center for Research in FOP & Related Disorders, The Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Abstract

Clinical trials for orphan diseases are critical for developing effective therapies. One such condition, fibrodysplasia ossificans progressiva (FOP; MIM#135100), is characterized by progressive heterotopic ossification (HO) that leads to severe disability. Individuals with FOP are extremely sensitive to even minor traumatic events. There has been substantial recent interest in clinical trials for novel and urgently-needed treatments for FOP. The International Clinical Council on FOP (ICC) was established in 2016 to provide consolidated and coordinated advice on the best practices for clinical care and clinical research for individuals who suffer from FOP. The Clinical Trials Committee of the ICC developed a focused list of key considerations that encompass the specific and unique needs of the FOP community - considerations that are endorsed by the entire ICC. These considerations complement established protocols for developing and executing robust clinical trials by providing a foundation for helping to ensure the safety of subjects with FOP in clinical research trials.

Keywords: Fibrodysplasia ossificans progressiva (FOP); patient safety; rare disease clinical trials.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Bone Remodeling / drug effects*
Clinical Trials as Topic / methods*
Consensus
Humans
Myositis Ossificans / diagnosis
Myositis Ossificans / drug therapy*
Myositis Ossificans / physiopathology
Ossification, Heterotopic / diagnosis
Ossification, Heterotopic / drug therapy*
Ossification, Heterotopic / physiopathology
Patient Safety
Patient Selection
Research Design*
Stakeholder Participation