NCT03164928已完成3 期
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
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Amgen
- 入组人数
- 24
- 试验地点
- 38
- 主要终点
- Change From Baseline in Lumbar Spine BMD Z-score as Assessed by Dual-energy X-ray Absorptiometry (DXA) at 12 Months
研究概览
简要总结
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Double-blind
入排标准
- 年龄范围
- 5 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- 未提供
研究组 & 干预措施
Placebo
Other
SC Q6M placebo
干预措施: Placebo (Other)
Denosumab
Experimental
1 mg/kg BW (up to a maximum of 60 mg) SC Q6M
干预措施: Denosumab (Drug)
结局指标
主要结局
Change From Baseline in Lumbar Spine BMD Z-score as Assessed by Dual-energy X-ray Absorptiometry (DXA) at 12 Months
时间窗: Baseline and 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.
次要结局
- Change From Baseline in Growth Velocity Z-score (Height) at 12, 24, and 36 Months(Baseline and Month 12, 24, and 36)
- Change From Baseline in Growth Velocity Z-score (BMI) at 12, 24, and 36 Months(Baseline and Month 12, 24, and 36)
- Change From Baseline in Proximal Femur BMD Z-score as Assessed by DXA at 6, 12, 18, 24, and 36 Months(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(Month 12, 24, and 36)
- Number of Participants With Improving Vertebral Fractures at 12, 24, and 36 Months(Month 12, 24, and 36)
- Change From Baseline in Childhood Health Assessment Questionnaire (CHAQ) Disability Index Score at 12, 24, and 36 Months(Baseline and Month 12, 24, and 36)
- Change From Baseline in Wong-Baker FACES Pain Rating Scale (WBFPRS) at 12, 24, and 36 Months(Baseline and Month 12, 24, and 36)
- Change From Baseline in Growth Velocity Z-score (Weight) at 12, 24, and 36 Months(Baseline and Month 12, 24, and 36)
- Change From Baseline in Lumbar Spine BMD Z-score as Assessed by DXA at 6, 18, 24, and 36 Months(Baseline and 6, 18, 24, and 36 Months)
- Change From Baseline in CHQ-PF-50 Psychological Summary Score at 12, 24, and 36 Months(Baseline and Month 12, 24, and 36)
- Number of Participants With New and Worsening Vertebral and Non-vertebral Fractures at 12, 24, and 36 Months(Month 12, 24, and 36)
- Change From Baseline in Child Health Questionnaire-Parent Form-50 (CHQ-PF-50) Physical Summary Score at 12, 24, and 36 Months(Baseline and month 12, 24, and 36)
- Mean Serum Concentration of Denosumab(Day 1, Day 10, Day 30, Month 3, Month 6, Month 12, and Month 18)
研究者
研究点 (38)
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