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

Amgen24 enrolled

Overview

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).

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

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

Interventions

DenosumabDRUG

1mg/kg BW (up to a maximum of 60 mg) SC Q6M

PlaceboOTHER

SC Q6M placebo

Eligibility

Sex: ALLMin age: 5 YearsMax age: 17 Years

Medical Language ↔ Plain English

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

Locations (38)

Outcomes

Primary Outcomes

Change From Baseline in Lumbar Spine BMD Z-score as Assessed by Dual-energy X-ray Absorptiometry (DXA) at 12 Months

Lumbar spine BMD was assessed by DXA and analyzed by analysis of covariance (ANCOVA) including treatment (denosumab vs placebo), baseline age, and baseline BMD z-score. DXA results were converted to z-scores, indicating number of standard deviations from the reference population's mean, with 0 denoting the mean. Positive changes from baseline signify lumbar spine BMD improvement.

Time frame: Baseline and 12 Months

Secondary Outcomes

Change From Baseline in Lumbar Spine BMD Z-score as Assessed by DXA at 6, 18, 24, and 36 Months

Lumbar spine BMD was assessed by DXA and analyzed by repeated measures analysis with randomization group, visit, baseline age, and baseline BMD z-score as fixed effects. Treatment-by-visit was included as an interaction term. DXA results were converted to z-scores, indicating number of standard deviations from the reference population's mean, with 0 denoting the mean. Positive changes from baseline signify lumbar spine BMD improvement.

Time frame: Baseline and 6, 18, 24, and 36 Months

Change From Baseline in Proximal Femur BMD Z-score as Assessed by DXA at 6, 12, 18, 24, and 36 Months

Proximal femur (total hip and femoral neck) BMD was assessed by DXA and analyzed by repeated measures analysis with randomization group, visit, baseline age, and baseline BMD z-score as fixed effects. Treatment-by-visit was included as an interaction term. DXA results were converted to z-scores, indicating number of standard deviations from the reference population's mean, with 0 denoting the mean. Positive changes from baseline signify proximal femur BMD improvement.

Time frame: Baseline and 6, 12, 18, 24, and 36 Months

Number of Participants With X-ray Confirmed Long-bone Fractures and/or Vertebral Fractures at 12, 24, and 36 Months

Number of participants who have at least one long bone fracture or vertebral fracture, and number of participants who have more than one long bone fracture or vertebral fracture.

Data from ClinicalTrials.gov

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