NCT02352753终止3 期
To Evaluate the Effect of Denosumab in Lumbar Spine Bone Mineral Density (BMD) Z-score at 12 Months, as Assessed by Dual-energy X-ray Absorptiometry (DXA), in Children 2 to 17 Years of Age (at the Time of Screening) on a 3-Month Dosing Regimen With OI
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 发起方
- Amgen
- 入组人数
- 153
- 试验地点
- 1
- 主要终点
- Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) Z-Score at 12 Months
研究概览
简要总结
This is a prospective, multicenter, single-arm study in children 2 to 17 years of age with OI to evaluate efficacy and safety of denosumab.
详细描述
To evaluate the effect of denosumab in lumbar spine bone mineral density (BMD) Z-score at 12 months, as assessed by dual-energy X-ray absorptiometry (DXA), in children 2 to 17 years of age (at the time of screening) on a 3-Month Dosing Regimen with osteogenesis imperfecta (OI)
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 2 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Clinical diagnosis of OI defined as a clinical history consistent with type I-IV OI Clinical severity of OI as defined by 2 or more prevalent vertebral compression fractures; OR1 prevalent vertebral compression fracture and 1 or more nonvertebral fractures within the previous 2 years; OR 3 or more fractures within the previous 2 years.
排除标准
- •Inability or unwillingness to comply with the requirements for frequent calcium and phosphorus monitoring for 14 days after the first dose of denosumab (only applies to the first 5 subjects age 11 to17 enrolled in the study and the first 5 subjects of any age meeting the criteria for increased bone turnover
- •Currently unhealed fracture or osteotomy as defined by orthopedic opinion
- •Osteotomy within 5 months of screening
- •Evidence of untreated oral cavities or oral infections
- •Recent or planned invasive dental procedure
- •Surgical tooth extraction which has not healed by screening
- •History of an electrophoresis pattern inconsistent with type I to IV OI
- •History of genetic testing results inconsistent with type I to IV OI
- •Abnormalities of the following per central laboratory reference ranges at screening: Serum albumin corrected calcium < lower limit of normal (LLN) Serum vitamin D < 20 ng/mL; re-screening for Vitamin D level < 20 ng/mL will be allowed, after adequate supplementation
- •Aspartate aminotransferase (AST), alanine aminotransferase (ALT) > 1.5 x upper limit of normal (ULN)
- •Total bilirubin (TBL) > 1.5 x ULN (subjects with Gilbert syndrome are eligible)
- •Serum phosphorus < LLN
- •Serum alkaline phosphatase > 20% above the ULN or > 20% below the LLN
- •Estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 (calculated bythe Schwartz equation at screening) Evidence of any of 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
- •Current, uncontrolled hypercalcemia (albumin-corrected serum Ca >10% ULN)
- •History of osteomalacia or rickets (chart review)
- •Other bone diseases that affect bone metabolism (eg, osteoporosis pseudoglioma syndrome, idiopathic juvenile osteoporosis, osteopetrosis, hypophosphatasia)
- •History of autoimmune disease
- •History of rare hereditary problems of fructose intolerance
- •Positive blood screen for human immunodeficiency virus -1 or -2 antibody
- •Positive blood screen for hepatitis B surface antigen or hepatitis C antibody
- •Received other osteoporosis treatment or bone active treatment with the following guidelines:
- •Prior treatment with
- •denosumab
- •fluoride or strontium for bone disease (fluoride taken for routine dental care is permitted)
- •parathyroid hormone (PTH) or PTH derivatives within 12 months prior to screening
- •zoledronic acid within 6 months prior to screening
- •oral bisphosphonates or intravenous bisphosphonates other than zoledronic acid if the first dose of denosumab would be before their next scheduled bisphosphonate dose would have been given
- •Administration of systemic glucocorticoids (≥ 5.0 mg prednisone equivalents/day for more than 10 days) within 3 months of screening.
- •Topical and inhaled glucocorticoids will be allowed
- •Administration of any of the following treatment within 3 months of screening:
- •Growth hormone (subjects on stable dose of growth hormone for at least 3 months prior to screening will be allowed)
- •Currently receiving treatment in another investigational drug study, or less than 30 days since ending treatment on another investigational drugstudy(s), or current or planned participation in a clinical trial that would preclude compliance with study requirements Other inclusion/exclusion criteria may apply.
研究组 & 干预措施
Denosumab
Experimental
Participants received denosumab 1 mg/kg (up to a maximum of 60 mg) subcutaneously every 6 months (Q6M) for up to 36 months.
Early efficacy and PK data from Q6M dosing supported adjustment of the dosing regimen from Q6M to every 3 months (Q3M). Participants enrolled and still receiving denosumab were transitioned from Q6M to Q3M dosing schedule. Participants could transition to Q3M dosing schedule up to and including the date they attended for their month 36 visit under the Q6M dosing regimen. Those participants received denosumab during the Q3M dosing regimen for 12 months. Participants who transition to Q3M at month 18 of the Q6M dosing regimen received denosumab Q3M for up to 18 months.
干预措施: Denosumab (Drug)
结局指标
主要结局
Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) Z-Score at 12 Months
时间窗: Baseline and 12 months
Lumbar spine BMD was measured by dual-energy X-ray absorptiometry (DXA) adjusted for age, sex, and race/ethnicity. The results were then converted to Z-scores. The Z-score indicated the number of standard deviations away from the reference population and a score of 0 is equal to the mean. Positive changes from Baseline indicated an improvement in lumbar spine BMD.
次要结局
- Change From Baseline in Proximal Femur BMD Z-score at 6 and 12 Months(Baseline, 6 and 12 months)
- Percentage of Participants With at Least 1 X-ray Confirmed Long Bone or New and Worsening Vertebral Fracture(Q6M Dosing Regimen: Last 12 months of treatment (median treatment duration was 730.0 days); Q3M Dosing Regimen: Day 1 up to 12 months)
- Change From Baseline in Wong-Baker Faces Pain Rating Scale (WBFPRS) at 12 Months(Baseline and 12 months)
- Serum Bone Turnover Marker (BTM) - Serum Type I Collagen C Telopeptide(Baseline and Days 10 and 30, and Months 3, 6, 9, 12, 15 and 18)
- BTM - Bone-specific Alkaline Phosphatase (BSAP)(Baseline and Days 10 and 30, and Months 3, 6, 9, 12, and 15)
- Change From Baseline in Lumbar Spine BMD Z-score at 6 Months(Baseline and 6 months)
- Percentage of Participants With at Least 1 X-ray Confirmed New and Worsening Vertebral Fracture(Q6M Dosing Regimen: Last 12 months of treatment (median treatment duration was 730.0 days); Q3M Dosing Regimen: Day 1 up to 12 months)
- Percentage of Participants Wth at Least 1 X-ray Confirmed Improving Vertebral Fracture(Q3M Dosing Regimen: Baseline up to 12 months)
- Change From Baseline in Childhood Health Assessment Questionnaire (CHAQ) Disability Index Score at 12 Months(Baseline and 12 months)
- Percentage of Participants With at Least 1 X-ray Confirmed New Vertebral Fracture(Q6M Dosing Regimen: Last 12 months of treatment (median treatment duration was 730.0 days); Q3M Dosing Regimen: Day 1 up to 12 months)
- Change From Baseline in Child Health Questionnaire-Parent Form Physical Summary Score (CHQ-PF-50) at 12 Months(Baseline and 12 months)
- Percentage of Participants With at Least 1 Vertebral and Nonvertebral Fracture(Q6M Dosing Regimen: Last 12 months of treatment (median treatment duration was 730.0 days); Q3M Dosing Regimen: Day 1 up to 12 months)
- Change From Baseline in CHQ-PF-50 Psychological Summary Score at 12 Months(Baseline and 12 months)
- Serum Concentration of Denosumab(Days 1 (predose), 10, 30, and 60, & weeks 12, 24, 36, 48, 60, 72 (end of study visit), early termination visit, & follow-up visit 12 weeks after last dose (average duration of treatment: 231 days))
- Change From Baseline in Growth Velocity at 12 Months(Baseline and 12 months)
研究者
研究点 (1)
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