Safety and Efficiency of Denosumab in Pediatric Subjects With Glucocorticoid-induced Osteoporosis

Inclusion Criteria:

1. Male or female subjects, age 5 to 17 years, inclusive, at the time of informed consent.
2. 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])
3. 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)
4. 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

1. 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)
2. Subjects who are on systemic GC only as replacement therapy for adrenal insufficiency are not eligible for the study
3. Treatment with systemic GC (intravenous or oral) of any duration for the underlying non malignant condition(s) within the 12 months prior to screening
4. Prepubertal children should be expected to require significant GC use during the study, per investigator opinion

Exclusion criteria will include the following:

1. Current hyperthyroidism (unless well controlled on stable antithyroid therapy)
2. Current clinical hypothyroidism (unless well controlled on stable thyroid replacement therapy)
3. History of hyperparathyroidism
4. Current hypoparathyroidism
5. Duchenne muscular dystrophy with symptomatic cardiac abnormality
6. Current malabsorption
7. Active infection or history of infections

History of malignancy

1. 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)
2. Current adrenal insufficiency as the sole indication for GC therapy
3. Duchenne muscular dystrophy with symptomatic cardiac abnormality
4. Current malabsorption (in children with serum albumin -lower limit of normal [LLN], malabsorption should be clinically ruled out by the investigator to confirm eligibility)
5. Known intolerance to calcium or vitamin D supplements
6. Active infection or history of infections, defined as follows:
7. Any active infection for which systemic anti-infectives were used within 4 weeks prior to screening
8. Serious infection, defined as requiring hospitalization or intravenous anti infectives within 8 weeks prior to screening
9. Recurrent or chronic infection or other active infection that, in the opinion of the investigator, might compromise the safety of the subject