safety and efficiency of denosumab in pediatric subjects with glucocorticoid-induced osteoporosis

Conditions: Evaluate the Safety and Efficacy of Denosumab in Pediatric Subjects With; Glucocorticoid-induced Osteoporosis

Summary: to evaluate the effect of denosumab on lumbar spine bone mineral density (bmd) z-score as assessed by dual-energy x-ray absorptiometry (dxa) at 12 months in children 5 to 17 year of age with glucocorticoid (gc)-induced osteoporosis (giop).


Eligibility criteria:
inclusion criteria: * male or female subjects, age 5 to 17 years, inclusive, at the time of informed consent. * clinical diagnosis of giop as defined by the following (and consistent with the international society for clinical densitometry definition of osteoporosis in children and adolescents \[bishop et al, 2014\]) * a confirmed diagnosis of non-malignant condition(s) requiring treatment with systemic gc (including, but not limited to, chronic rheumatologic, gastrointestinal, neurologic, respiratory, and/or nephrological conditions) * subjects who are on systemic gc only as replacement therapy for adrenal insufficiency are not eligible for the study - treatment with systemic gc (intravenous or oral) of any duration for the underlying non-malignant condition(s) within the 12 months prior to screening * evidence of at least 1 vertebral compression fracture of genant grade 1 or higher, as assessed by the central imaging vendor on lateral spine x-rays performed at screening or within 2 months prior to screening; or, in the absence of vertebral compression fractures, presence of both clinically significant fracture history (ie, ≥ 2 long-bone fractures by age 10 years or ≥ 3 long-bone fractures at any age up to 17 years) and lumbar spine bmd z-score ≤ -2.0, as assessed by the central imaging vendor. • subject's legally acceptable representative has provided informed consent when the subject is legally too young to provide informed consent and the subject has provided assent based on local regulations and/or guidelines prior to any study-specific activities/procedures being initiated * a confirmed diagnosis of non-malignant condition(s) requiring treatment with systemic gc (including, but not limited to, chronic rheumatologic, gastrointestinal, neurologic, respiratory, and/or nephrological conditions) * subjects who are on systemic gc only as replacement therapy for adrenal insufficiency are not eligible for the study * treatment with systemic gc (intravenous or oral) of any duration for the underlying non malignant condition(s) within the 12 months prior to screening * prepubertal children should be expected to require significant gc use during the study, per investigator opinion exclusion criteria will include the following: * current hyperthyroidism (unless well controlled on stable antithyroid therapy) * current clinical hypothyroidism (unless well controlled on stable thyroid replacement therapy) * history of hyperparathyroidism * current hypoparathyroidism * duchenne muscular dystrophy with symptomatic cardiac abnormality * current malabsorption * active infection or history of infections * history of malignancy * any causes of primary or secondary osteoporosis (other than gc use), or previous exposure to non-gc medications, which the investigator considers to have been a major factor contributing to the patient's fracture(s) * current adrenal insufficiency as the sole indication for gc therapy * duchenne muscular dystrophy with symptomatic cardiac abnormality * current malabsorption (in children with serum albumin -lower limit of normal \[lln\], malabsorption should be clinically ruled out by the investigator to confirm eligibility) * known intolerance to calcium or vitamin d supplements * active infection or history of infections, defined as follows: * any active infection for which systemic anti-infectives were used within 4 weeks prior to screening * serious infection, defined as requiring hospitalization or intravenous anti infectives within 8 weeks prior to screening * recurrent or chronic infection or other active infection that, in the opinion of the investigator, might compromise the safety of the subject

Keywords: denosumab pediatric giop glucocorticoid-induced osteoporosis