Patient inclusion and exclusion criteria
HO lesions, non-traumatic bleeding, swelling, FOP disease, toxicity, cancer, episodic soft-tissue swelling, congenital malformation, epistaxis, FOP flare-ups, pain, Willebrand’s factor deficiency, FOP, HO
CANCER, HEMOPHILIA A, LYMPHATIC DISEASE, EPISTAXIS, BLEEDING DIATHESIS
The study population included male and female patients aged 18–60 years at screening with a clinical diagnosis of FOP (based on findings of congenital malformation of the great toes, episodic soft-tissue swelling and/or progressive HO) and a history of FOP disease activity (defined as pain, swelling, stiffness and other signs/symptoms associated with FOP flare-ups; or worsening of joint function, or radiographic progression of HO (increase in site or number of HO lesions) with/without being associated with flare-up episodes) within 1 year of screening, plus documentation of an Patients were excluded if they met the following exclusion criteria:Relevant concomitant illness or history of relevant illness such as but not limited to cardiac, renal, rheumatologic, neurologic, psychiatric, endocrine, metabolic or lymphatic disease.Previous history or diagnosis of cancer.Used bisphosphonate therapies within 1 year of screening, as these medications alter bone metabolism and would confound the primary efficacy analysis.Concurrent participation in another interventional clinical study, or a non-interventional study with radiographic measures or invasive procedures (for example, collection of blood or tissue samples). Participation in the FOP Connection Registry or other studies in which participants complete study questionnaires was allowed.Treatment with another investigational drug, denosumab, imatinib or isotretinoin in the last 30 d or within five half-lives of the investigational drug, whichever was longer.To address a potential risk of embryotoxicity or male reproductive organ toxicity, the protocol also excluded pregnant or breastfeeding females, as well as males and females of child-bearing potential who were unwilling to practice highly effective contraception.To address a potential risk of epistaxis identified during the study in period 1, the following exclusion criteria were added (protocol amendment no. 3):Patients on concomitant antiplatelet therapy (for example, clopidogrel), anti-coagulants (for example, warfarin, heparin, factor Xa inhibitor or thrombin inhibitors) in the last 30 d or within five half-lives of the therapy, whichever was longer. Low-dose acetylsalicylic acid (aspirin) was acceptable.Patients with a history of severe, non-traumatic bleeding requiring transfusion or hospitalization for hemodynamic compromise.Patients with a known pre-existing medical history of a bleeding diathesis (for example, hemophilia A, von Willebrand’s factor deficiency, platelet count ≤20 × 109 lDetailed inclusion and exclusion criteria are provided in the full protocol available online.Patients on concomitant antiplatelet therapy (for example, clopidogrel), anti-coagulants (for example, warfarin, heparin, factor Xa inhibitor or thrombin inhibitors) in the last 30 d or within five half-lives of the therapy, whichever was longer. Low-dose acetylsalicylic acid (aspirin) was acceptable.Patients with a history of severe, non-traumatic bleeding requiring transfusion or hospitalization for hemodynamic compromise.Patients with a known pre-existing medical history of a bleeding diathesis (for example, hemophilia A, von Willebrand’s factor deficiency, platelet count ≤20 × 109 lDetailed inclusion and exclusion criteria are provided in the full protocol available online.