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

A Phase 3 Randomized, Double-blind, Placebo-controlled, Parallel-group Study to Evaluate the Safety and Efficacy of Denosumab in Pediatric Subjects With Glucocorticoid-induced Osteoporosis

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).

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