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

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.

PMID: 30281842
PMCID: PMC6533500
DOI: 10.1111/bcp.13777

Review

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

Edward C Hsiao et al. Br J Clin Pharmacol. 2019 Jun.

. 2019 Jun;85(6):1199-1207.

doi: 10.1111/bcp.13777. Epub 2018 Nov 6.

Authors

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.

PMID: 30281842
PMCID: PMC6533500
DOI: 10.1111/bcp.13777

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.

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Conflict of interest statement

E.C.H., M.D.R., M.Z., M.A.M., R.J.P., C.N., R.K., G.B., M.A.B., C.D.C., P.D., N.H., F.S.K. and E.M.W.E. receive clinical trials research support from Clementia Pharmaceuticals. R.J.D. and R.M. are consultants for Clementia Pharmaceuticals. M.Z. is on the data safety monitoring board for Clementia Pharmaceuticals. E.C.H., M.A.M., R.J.P., M.D.R., M.A.B., E.M.W.E., R.K., and F.S.K. receive clinical trials research funding from Regeneron Pharmaceuticals. R.M. is a paid consultant for Regeneron Pharmaceuticals. E.C.H., C.N., R.K., G.B., M.A.B., C.D.C., M.D.R., R.J.P., M.Z., P.D., C.S., N.H., K.Z., R.M., F.S.K. and E.M.W.E. also serve as unpaid volunteers on the International FOP Association Medical Registry Advisory Board. E.C.H., E.M.W.E., R.J.P. and F.S.K. serve as unpaid volunteers on the FOP Biomarker Consortium. E.C.H. also serves as an unpaid volunteer on the Fibrous Dysplasia Foundation Medical Advisory Board. M.D.R. is a consultant and/or speaker for Sanofi‐Genzyme, Shire, Alexion, Biomarin, Chiesi, Clementia Pharmaceuticals, and Regeneron Pharmaceuticals. M.D.R. receives clinical trial research support from Sanofi, Genzyme, Alexion, Enzyvant. A.C. is a trustee of the Radiant Hope Foundation and trustee of the Ian Cali FOP Research Fund ‐ PENN Medicine ‐ Center for Research in FOP & Related Disorders, and is an unpaid volunteer with Clementia Pharmaceuticals Burden of Illness Advisory Group. P.D. is an unpaid medical advisor for FOP Brazil. M.A.M. and M.Z. are nonpaid consultants for BioCryst. E.M.W.E. is an advisor for AstraZenica and Blueprint Pharmaceuticals. Z.G. is a nonpaid consultant for the Natural History Study on FOP Board. R.K. also receives research support from UltraGenyx; is a paid consultant for Clementia Pharmaceuticals, Regeneron Pharmaceuticals, UltraGenyx, Internis, and Alexion; and is a nonpaid member of the Medical Advisory Board for the UK Brittle Bone Society.

The authors thank the Center for Research in FOP & Related Disorder at the University of Pennsylvania for supporting the International Clinical Council for FOP (ICC). E.C.H. received salary support from the University of California – San Francisco Department of Medicine to support this work. F.S.K. received support from the Isaac & Rose Nassau Professorship of Orthopaedic Molecular Medicine at the University of Pennsylvania. R.J.P. received support from the Robert and Arlene Kogod Professorship and M.A.M. received funding from the Ian Cali FOP Clinical Scholarship. E.C.H. and R.J.P. received support from the Radiant Hope Foundation.

References

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

Affiliations

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

Authors

Affiliations

Abstract

Conflict of interest statement

References

Publication types

MeSH terms

LinkOut - more resources

Full Text Sources

Medical