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

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.

Self-reported baseline phenotypes from the International Fibrodysplasia Ossificans Progressiva (FOP) Association Global Registry.

A global, patient-reported registry has been established to characterize the course of disease and track clinical outcomes in patients with fibrodysplasia ossificans progressiva (FOP), an ultra-rare genetic condition of progressive heterotopic ossification (HO) that results in ankylosis of joints and renders most affected individuals immobile by the second decade of life. Here, we present baseline phenotypes on 299 patients (median age 21 years; range 0.1 to 78 years) from 54 countries based on aggregate data from the International FOP Association (IFOPA) Global Registry (the "FOP Registry"). The mean current age of the patients is 23.7 years (range, 0.1 to 78 years). Baseline characteristics are presented for FOP diagnosis, HO, flare-ups and precedent events, system-based prevalent symptomatology, encounters with medical and dental care providers, Patient Reported Outcomes Measurement Information System (PROMIS) Global Health Scale scores, physical function, as well as the use of aids, assistive devices, and adaptations. Correlations of PROMIS Global Health scores with HO burden and physical function are calculated. Associations of joint mobility with PROMIS Global Health scores, physical function, and use of aids, assistive devices, and adaptations are summarized. Overall, the FOP Registry database contains a broad sample of the global FOP patient population, providing a useful tool for expanding knowledge of FOP, designing clinical trials and facilitating evidence-based decisions about the optimal monitoring and management of affected individuals.