A Multicenter, International, Randomized, Double-blind, Alendronate-controlled Study to Determine the Efficacy and Safety of Romosozumab in the Treatment of Postmenopausal Women With Osteoporosis
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Amgen
- 入组人数
- 4,093
- 试验地点
- 1
- 主要终点
- Percentage of Participants With New Vertebral Fractures Through Month 24
研究概览
简要总结
The purpose of this study is to determine if treatment is effective in preventing fractures in women with postmenopausal osteoporosis.
详细描述
In this trial, women were randomly assigned in a 1:1 ratio to receive monthly subcutaneous romosozumab or weekly oral alendronate for 12 months. Randomization was stratified according to age (<75 vs. ≥75 years). After completion of the double-blind treatment period, all the participants were to receive open-label weekly oral alendronate until the end of the trial, with blinding to the initial treatment assignment maintained.
The primary analysis was performed when clinical fracture events had been confirmed in at least 330 participants and all the participants had completed the month 24 visit. The study was to continue in an event-driven manner until at least 440 participants experienced a nonvertebral fracture or if the superiority of romosozumab was proven for nonvertebral fractures at the primary analysis.
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)
入排标准
- 年龄范围
- 55 Years 至 90 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Postmenopausal women who meet at least one of the following bone mineral density (BMD) and fracture criteria:
- •BMD T-score at the total hip or femoral neck of ≤ -2.50 and EITHER:
- •at least 1 moderate (semiquantitative grade [SQ]2) or severe (SQ3) vertebral fracture OR
- •at least 2 mild (SQ1) vertebral fractures OR
- •BMD T-score at the total hip or femoral neck of ≤ -2.00 and EITHER:
- •at least 2 moderate (SQ2) or severe (SQ3) vertebral fractures OR
- •a fracture of the proximal femur that occurred within 3 to 24 months prior to randomization.
排除标准
- •History of metabolic or bone disease (except osteoporosis)
- •Use of agents affecting bone metabolism
- •Vitamin D insufficiency
- •History of solid organ or bone marrow transplants
- •Hyper- or hypocalcemia
- •Hyper- or hypothyroidism
- •Hyper- or hypoparathyroidism
- •Possible signs of intolerance to alendronate
研究组 & 干预措施
Alendronate/Alendronate
Participants received 70 mg alendronate once a week and placebo to romosozumab subcutaneously once a month for the first 12 months. After completion of the 12-month double-blind treatment period participants continued to receive 70 mg alendronate once a week until the end of the study.
干预措施: Alendronate (Drug)
Alendronate/Alendronate
Participants received 70 mg alendronate once a week and placebo to romosozumab subcutaneously once a month for the first 12 months. After completion of the 12-month double-blind treatment period participants continued to receive 70 mg alendronate once a week until the end of the study.
干预措施: Placebo to Romosozumab (Drug)
Romosozumab/Alendronate
Participants received 210 mg romosozumab subcutaneously once a month and placebo to alendronate orally once a week for the first 12 months. After completion of the 12-month double-blind treatment period participants received 70 mg alendronate once a week until the end of the study.
干预措施: Romosozumab (Biological)
Romosozumab/Alendronate
Participants received 210 mg romosozumab subcutaneously once a month and placebo to alendronate orally once a week for the first 12 months. After completion of the 12-month double-blind treatment period participants received 70 mg alendronate once a week until the end of the study.
干预措施: Alendronate (Drug)
Romosozumab/Alendronate
Participants received 210 mg romosozumab subcutaneously once a month and placebo to alendronate orally once a week for the first 12 months. After completion of the 12-month double-blind treatment period participants received 70 mg alendronate once a week until the end of the study.
干预措施: Placebo to Alendronate (Drug)
结局指标
主要结局
Percentage of Participants With New Vertebral Fractures Through Month 24
时间窗: 24 months
All fracture assessments were performed by blinded central imaging readers. New vertebral fractures occurred when there was ≥ 1 grade increase from the previous grade of 0 in any vertebra from T4 to L4 using the Genant Semiquantitative Scoring method based on assessment of x-rays according to the following scale: * Grade 0 (Normal) = no fracture; * Grade 1 (Mild) = mild fracture, 20 to 25% reduction in vertebral height (anterior, middle, or posterior); * Grade 2 (Moderate) = moderate fracture, 25 to 40% reduction in anterior, middle, and/or posterior height; * Grade 3 (Severe) = severe fracture, greater than 40% reduction in anterior, middle, and/or posterior height. Incident vertebral fractures were confirmed by a second independent reader using the Semiquantitative method.
Percentage of Participants With a Clinical Fracture at the Primary Analysis
时间窗: The primary analysis was performed when clinical fracture events had been confirmed in at least 330 patients and all participants had completed the month 24 visit. The median follow-up was 2.7 years (interquartile range, 2.2 to 3.3).
All fracture assessments were performed by blinded central imaging readers. Clinical fractures included clinical vertebral and nonvertebral fractures (excluding skull, facial, mandible, cervical vertebrae, thoracic vertebrae, lumbar vertebrae, metacarpus, finger phalanges, and toe phalanges) that were associated with signs and/or symptoms indicative of a fracture. Clinical vertebral fractures were included regardless of trauma severity or pathologic fractures; nonvertebral fractures associated with high trauma severity or pathologic fractures were excluded.
次要结局
- Percentage of Participants With a Major Nonvertebral Fracture at the Primary Analysis(The primary analysis was performed when clinical fracture events had been confirmed in at least 330 patients and all participants had completed the month 24 visit. The median follow-up was 2.7 years (interquartile range, 2.2 to 3.3).)
- Percentage of Participants With a Hip Fracture at the Primary Analysis(The primary analysis was performed when clinical fracture events had been confirmed in at least 330 patients and all participants had completed the month 24 visit. The median follow-up was 2.7 years (interquartile range, 2.2 to 3.3).)
- Percentage of Participants With a Hip Fracture Through Month 24(24 months)
- Percentage of Participants With New Vertebral Fractures Through Month 12(12 months)
- Percentage of Participants With a Major Osteoporotic Fracture Through Month 12(12 months)
- Percentage of Participants With a Clinical Vertebral Fracture Through Month 12(12 months)
- Percent Change From Baseline in Bone Mineral Density of the Femoral Neck at at Month 24(Baseline and month 24)
- Percent Change From Baseline in Bone Mineral Density of the Femoral Neck at Month 36(Baseline and month 36)
- Percentage of Participants With Any Fracture at the Primary Analysis(The primary analysis was performed when clinical fracture events had been confirmed in at least 330 patients and all participants had completed the month 24 visit. The median follow-up was 2.7 years (interquartile range, 2.2 to 3.3).)
- Percentage of Participants With Multiple New or Worsening Vertebral Fractures Through Month 24(24 months)
- Percentage of Participants With a Clinical Fracture Through Month 24(24 months)
- Percentage of Participants With a Nonvertebral Fracture Through Month 12(12 months)
- Percentage of Participants With a Nonvertebral Fracture at the Primary Analysis(The primary analysis was performed when clinical fracture events had been confirmed in at least 330 patients and all participants had completed the month 24 visit. The median follow-up was 2.7 years (interquartile range, 2.2 to 3.3).)
- Percentage of Participants With a New or Worsening Vertebral Fracture Through Month 24(24 months)
- Percentage of Participants With a Clinical Fracture Through Month 12(12 months)
- Percent Change From Baseline in Bone Mineral Density of the Total Hip at Month 24(Baseline and month 24)
- Percent Change From Baseline in Bone Mineral Density of the Total Hip at Month 36(Baseline and month 36)
- Percentage of Participants With a Clinical Vertebral Fracture Through Month 24(24 months)
- Percentage of Participants With Any Fracture Through Month 12(12 months)
- Percent Change From Baseline in Bone Mineral Density at the Femoral Neck at Month 12(Baseline and month 12)
- Percentage of Participants With a Nonvertebral Fracture Through Month 24(24 months)
- Percentage of Participants With a Hip Fracture Through Month 12(12 months)
- Percent Change From Baseline in Bone Mineral Density at the Lumbar Spine at Month 12(Baseline and month 12)
- Percent Change From Baseline in Bone Mineral Density of the Lumbar Spine at Month 36(Baseline and month 36)
- Percent Change From Baseline in Bone Mineral Density at the Lumbar Spine at Month 24(Baseline and month 24)
- Percent Change From Baseline in Bone Mineral Density at the Total Hip at Month 12(Baseline and month 12)