A Multi-center, Randomized, Double-blind, Placebo-controlled Study to Determine the Efficacy, Safety, and Tolerability of AMG 785 in Adults With a Fresh Unilateral Hip Fracture, Status Post Surgical Fixation
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Amgen
- 入组人数
- 332
- 试验地点
- 1
- 主要终点
- Timed-Up-and-Go (TUG) Over Week 6 Through Week 20
研究概览
简要总结
This is an international, multi-center study to determine the efficacy, safety, and tolerability of romosozumab (AMG 785) in adults with a fresh unilateral hip fracture, status post surgical fixation.
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 95 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Males and females, age 55 to 95 years
- •fresh unilateral low energy intertrochanteric or femoral neck fracture as the primary injury, confirmed by X-ray and in the opinion of the treating surgeon amenable to repair by internal fixation
- •internal fixation of the fracture with devices approved by local regulatory agency, performed no later than 7 days after injury for intertrochanteric or undisplaced femoral neck fractures and no later than 2 days after injury for displaced femoral neck fractures
- •intertrochanteric fracture: sliding hip screw or IM nail
- •femoral neck fracture: sliding hip screw or at least 3 cancellous screws
排除标准
- •severe symptomatic osteoarthritis of the lower extremity
- •inability to independently rise from armchair or walk 200 meters before hip fracture
- •presence of concomitant injuries such as rib fractures, wrist fractures, or acute symptomatic vertebral fractures which severely impair the ability to rise from a chair
- •associated extremity injuries including ipsilateral or contralateral fractures of the foot, tibia or fibula, wrist, humerus, femoral shaft, femoral head or hip dislocation, that may delay weight-bearing beyond one week after surgery
- •head-injury, as defined by Glasgow Coma Scale < 13 prior to randomization
- •use of bone grafts or bone substitutes at the time of fracture fixation
- •major polytrauma or significant axial trauma, with Injury Severity Score > 16
- •pathological fracture or history of metabolic or bone disease (except osteoporosis) that may interfere with the interpretation of the results, such as Paget's disease, rheumatoid arthritis, osteomalacia, osteopetrosis, ankylosing spondylitis, Cushing's disease, hyperprolactinemia
- •history of symptomatic spinal stenosis that has not been surgically corrected. If surgically corrected, the subject must be asymptomatic to be eligible for the study.
- •history of facial nerve paralysis
- •malignancy (except fully resected cutaneous basal cell or squamous cell carcinoma, cervical carcinoma in situ) within the last 5 years
- •history of solid organ or bone marrow transplants
- •evidence of elevated transaminases (≥ 2.0 x upper limits of normal) or significantly impaired renal function (creatinine clearance of ≤ 30 mL/min)
- •evidence of current hypercalcemia or hypocalcemia (outside of 1.1 x the normal range)
- •bone morphogenic proteins (BMP)-2 or BMP-7 at the time of definitive fracture fixation
研究组 & 干预措施
Placebo
Participants received placebo to romosozumab administered by subcutaneous injection on day 1 and at weeks 2, 6, and 12.
干预措施: Placebo (Drug)
Romosozumab 70 mg
Participants received 70 mg romosozumab administered by subcutaneous injection on day 1 and at weeks 2, 6, and 12.
干预措施: Romosozumab (Drug)
Romosozumab 140 mg
Participants received 140 mg romosozumab administered by subcutaneous injection on day 1 and at weeks 2, 6, and 12.
干预措施: Romosozumab (Drug)
Romosozumab 210 mg
Participants received 210 mg romosozumab administered by subcutaneous injection on day 1 and at weeks 2, 6, and 12.
干预措施: Romosozumab (Drug)
结局指标
主要结局
Timed-Up-and-Go (TUG) Over Week 6 Through Week 20
时间窗: Weeks 6, 12, 16, and 20
Functional healing was measured by the timed-up-and-go test (TUG) over Weeks 6 through 20. During this assessment, the clinician timed the participant while they stood up from a seated position in a chair, walked three meters, turned around, walked three meters back to the chair, and returned to the seated position. A TUG value of ten seconds or less was considered normal for a healthy elderly person. Higher TUG values after hip fracture have been shown to be a predictor of future falls. Least squares mean (LSM) estimates were based on a repeated measures model fitted with the log-transformed TUG values at weeks 2, 6, 12, 16, 20, 24, 36, 52 as the dependent variable and adjusted for treatment, randomized strata, gender, country category, pre-fracture community-dwelling status, pre-fracture walking aid use, quality of surgical fixation, visit, and treatment-by-visit interaction and back-transformed using the exponential transformation.
次要结局
- Timed-Up-and-Go (TUG) at Each Visit(Weeks 2, 6, 12, 16, 20, 24, 36, and 52)
- Radiographic Union Scale for Hip (RUSH) Score At Each Visit(Weeks 2, 6, 12, 16, 20, 24, 36, and 52)
- Time to Radiographic Healing(52 weeks)
- Hip Pain Score at Each Visit(Weeks 2, 6, 12, 16, 20, 24, 36, and 52)
- Harris Hip Score At Each Visit(Weeks 2, 6, 12, 16, 20, 24, 36, and 52)