An Open-label, Ascending Multiple-dose Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Romosozumab in Children and Adolescents With Osteogenesis Imperfecta
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Amgen
- 入组人数
- 25
- 试验地点
- 15
- 主要终点
- Time to Cmax (Tmax) of Romosozumab
研究概览
简要总结
The primary objective of this study is to evaluate the pharmacokinetics (PK) profile following multiple subcutaneous (SC) doses of romosozumab in children and adolescents with Osteogenesis Imperfecta (OI).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
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
- •Ambulatory male or female children 5 to less than 18 years of age upon entry into screening
- •Clinical diagnosis of OI defined as a clinical history consistent with type I-IV OI as determined by presence of expected phenotype and lack of additional features unrelated to type I-IV OI
- •Exclusion Criteria
- •History of an electrophoresis pattern inconsistent with type I to type IV OI
- •History of known mutation in a gene other than collagen type I alpha 1/collagen type I alpha 2 (COL1AI/COL1A2) causing OI or other metabolic bone disease
- •History of other bone diseases that affect bone metabolism (eg, osteoporosis pseudoglioma syndrome, idiopathic juvenile osteoporosis, osteopetrosis, hypophosphatasia)
- •History of Kawasaki disease, rheumatic myocarditis, ischemic cardiomyopathy, inherited cardiomyopathies, nephrotic syndrome, familial hypercholesterolemia, stroke, or any thromboembolic disorder
- •Unhealed fracture as defined by orthopedic opinion
- •Symptoms associated with skull abnormalities such as basilar invagination, basilar impression or Chiari malformation
- •Prior treatment with anti-sclerostin antibody, fluoride or strontium, parathyroid hormone (PTH) within 12 months prior to screening, denosumab within 12 months or zoledronic acid within 6 months prior to first dose
- •Less than 2 evaluable vertebrae by DXA evaluation in the region of interest, L1 - L4, as confirmed by the central imaging laboratory.
- •Clinically significant valvular heart disease based on local echocardiogram (ECHO) results.
排除标准
- 未提供
研究组 & 干预措施
Romosozumab: 12 - < 18 Years of Age
Participants will receive 1 of 3 dose levels of romosozumab. All participants also received calcium and vitamin D.
干预措施: Romosozumab (Drug)
Romosozumab: 12 - < 18 Years of Age
Participants will receive 1 of 3 dose levels of romosozumab. All participants also received calcium and vitamin D.
干预措施: Calcium (Dietary Supplement)
Romosozumab: 12 - < 18 Years of Age
Participants will receive 1 of 3 dose levels of romosozumab. All participants also received calcium and vitamin D.
干预措施: Vitamin D (Dietary Supplement)
Romosozumab: 5 - < 12 Years of Age
Participants will receive 1 of 3 dose levels of romosozumab. All participants also received calcium and vitamin D.
干预措施: Romosozumab (Drug)
Romosozumab: 5 - < 12 Years of Age
Participants will receive 1 of 3 dose levels of romosozumab. All participants also received calcium and vitamin D.
干预措施: Calcium (Dietary Supplement)
Romosozumab: 5 - < 12 Years of Age
Participants will receive 1 of 3 dose levels of romosozumab. All participants also received calcium and vitamin D.
干预措施: Vitamin D (Dietary Supplement)
结局指标
主要结局
Time to Cmax (Tmax) of Romosozumab
时间窗: Single blood samples were taken on days 1, 8, 15, 29, 57, 64, 71, 85, 113, and 169 (end of study); pre-specified PK analysis took place on Days 1 and 57
Median tmax values following Days 1 and 57 are presented.
Terminal Half-life of Romosozumab
时间窗: Single blood samples were taken on days 1, 8, 15, 29, 57, 64, 71, 85, 113, and 169 (end of study); pre-specified PK analysis took place on Day 57
Median terminal half-life values at Day 57 are presented.
Maximum Observed Serum Concentration (Cmax) of Romosozumab
时间窗: Single blood samples were taken on days 1, 8, 15, 29, 57, 64, 71, 85, 113, and 169 (end of study); pre-specified PK analysis took place on Days 1 and 57
Mean Cmax values following Days 1 and 57 are presented.
Area Under the Serum Concentration Time Curve (AUC) From Time 0 to Day 28 (AUC[0-28]) of Romosozumab
时间窗: Single blood samples were taken on days 1, 8, 15, 29, 57, 64, 71, and 85; pre-specified PK analysis took place on Days 1 and 57
Mean AUC(0-28) values following Days 1 and 57 are presented.
Accumulation Ratio of Romosozumab
时间窗: Single blood samples were taken on days 1, 8, 15, 29, 57, 64, 71, and 85; pre-specified PK analysis took place on Days 1 and 57
The accumulation ratio was calculated as AUC(0-28) at Day 57/AUC(0-28) at Day 1. Mean accumulation ratio values based on analysis at Days 1 and 57 are presented, as pre-specified.
次要结局
- Percentage Change From Baseline in Bone Mineral Density (BMD) of the Lumbar Spine(DXA scans were during screening (baseline) and at Day 85 and Day 169)
- Number of Participants With Changes From Baseline in Cranial Nerve VII Examination Findings at Day 57, Day 85, and Day 169(Baseline (Day 1), Day 57, Day 85, and Day 169)
- Number of Participants With Treatment-Emergent Adverse Events (TEAEs)(Day 1 to end of study (up to Day 169); median duration on study was 5.55 months)
- Percentage Change From Baseline in Serum Concentrations of Serum Type 1 Collagen C-Telopeptide (CTX)(Blood samples were taken Days 1 (baseline), 8, 15, 29, 57, 64, 71, 85, 113, and 169)
- Number of Participants With Anti-romosozumab Antibodies(Blood samples for anti-romosozumab antibodies were taken Day 1, Day 15, Day 29, Day 85, and Day 169)
- Percentage Change From Baseline in Serum Concentrations of Procollagen Type 1 N-terminal Propeptide (P1NP)(Blood samples were taken Days 1 (baseline), 8, 15, 29, 57, 64, 71, 85, 113, and 169)
- Percentage Change From Baseline in Bone Mineral Content (BMC) of the Lumbar Spine(DXA scans were during screening (baseline) and at Day 85 and Day 169)
- Percentage Change From Baseline in Lumbar Spine Bone Area(DXA scans were during screening (baseline) and at Day 85 and Day 169)
- Mean Change From Baseline in Lumbar Spine BMD Z-Score(DXA scans were during screening (baseline) and at Day 85 and Day 169)