Efficacy and Safety of Romosozumab Treatment in Postmenopausal Women With Osteoporosis

Phase 3

Completed

Conditions: Postmenopausal Osteoporosis

Interventions: Drug: Romosozumab
Drug: Placebo
Drug: Denosumab

Registration Number: NCT01575834

Lead Sponsor: Amgen

Brief Summary: The purpose of this study is to determine if treatment with romosozumab is effective in preventing fractures in women with postmenopausal osteoporosis

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 7180

Inclusion Criteria

Postmenopausal women with osteoporosis, defined as low bone mineral density (BMD T-score at the total hip or femoral neck of ≤ -2.50)

Exclusion Criteria

BMD T-score of ≤ -3.50 at the total hip or femoral neck
History of hip fracture
Any severe or more than 2 moderate vertebral fractures, as assessed by the central imaging based on lateral spine x-rays
Use of agents affecting bone metabolism
History of metabolic or bone disease (except osteoporosis)
Vitamin D insufficiency (vitamin D repletion and rescreening is permitted)
Current hyper- or hypocalcemia
Current, uncontrolled hyper- or hypothyroidism
Current, uncontrolled hyper- or hypoparathyroidism

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Romosozumab	Romosozumab	Participants received 210 mg romosozumab subcutaneous injections once a month for 12 months, followed by 60 mg denosumab subcutaneously once every 6 months for 24 months.
Romosozumab	Denosumab	Participants received 210 mg romosozumab subcutaneous injections once a month for 12 months, followed by 60 mg denosumab subcutaneously once every 6 months for 24 months.
Placebo	Placebo	Participants received placebo subcutaneous injections once a month for 12 months, followed by 60 mg denosumab subcutaneously once every 6 months for 24 months.
Placebo	Denosumab	Participants received placebo subcutaneous injections once a month for 12 months, followed by 60 mg denosumab subcutaneously once every 6 months for 24 months.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With New Vertebral Fracture Through Month 12	12 Months	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. The Genant semiquantitative scoring method was 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.
Percentage of Participants With New Vertebral Fracture Through Month 24	24 months	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. The Genant semiquantitative scoring method was 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.

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants With a Nonvertebral Fracture Through Month 12	12 Months	A nonvertebral fracture was defined as a fracture present on a copy of radiographs or other diagnostic images such as computerized tomography (CT) or magnetic resonance imaging confirming the fracture within 14 days of reported fracture image date recorded by the study site, and/or documented in a copy of the radiology report, surgical report, or discharge summary, excluding skull, facial, mandible, cervical vertebrae, thoracic vertebrae, lumbar vertebrae, metacarpus, finger phalanges, and toe phalanges. In addition, fractures associated with high trauma severity or pathologic fractures were excluded.
Percentage of Participants With a Clinical Fracture Through Month 12	12 Months	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.
Percentage of Participants With a New or Worsening Vertebral Fracture Through Month 12	12 Months	A new or worsening vertebral fracture was identified when there was a ≥ 1 grade increase from the previous grade in any vertebra from T4 to L4.
Percentage of Participants With a New or Worsening Vertebral Fracture Through Month 24	24 Months	A new or worsening vertebral fracture was identified when there was a ≥ 1 grade increase from the previous grade in any vertebra from T4 to L4.
Percentage of Participants With a Major Osteoporotic Fracture Through Month 12	12 Months	Major osteoporotic fractures included clinical vertebral fractures and fractures of the hip, forearm and humerus. Fractures associated with high trauma severity or pathologic fractures were excluded.
Percentage of Participants With a Nonvertebral Fracture Through Month 24	24 Months	A nonvertebral fracture was defined as a fracture present on a copy of radiographs or other diagnostic images such as computerized tomography (CT) or magnetic resonance imaging confirming the fracture within 14 days of reported fracture image date as recorded by the study site, and/or documented in a copy of the radiology report, surgical report, or discharge summary, excluding skull, facial, mandible, cervical vertebrae, thoracic vertebrae, lumbar vertebrae, metacarpus, finger phalanges, and toe phalanges. In addition, fractures associated with high trauma severity or pathologic fractures were excluded.
Percentage of Participants With a Clinical Fracture Through Month 24	24 Months	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.
Percentage of Participants With a Major Nonvertebral Fracture Through Month 12	12 Months	A major nonvertebral fracture was a subset of nonvertebral fractures including pelvis, distal femur (ie, femur excluding hip), proximal tibia (ie, tibia excluding ankle), ribs, proximal humerus (ie, humerus excluding elbow), forearm, and hip.
Percentage of Participants With a Hip Fracture Through Month 12	12 Months	Hip fractures were defined as a subset of nonvertebral fractures including fractures of the femur neck, femur intertrochanter, and femur subtrochanter.
Percentage of Participants With a Hip Fracture Through Month 24	24 Months	Hip fractures were defined as a subset of nonvertebral fractures including fractures of the femur neck, femur intertrochanter, and femur subtrochanter.
Percentage of Participants With a Major Nonvertebral Fracture Through Month 24	24 Months	A major nonvertebral fracture was a subset of nonvertebral fractures including pelvis, distal femur (ie, femur excluding hip), proximal tibia (ie, tibia excluding ankle), ribs, proximal humerus (ie, humerus excluding elbow), forearm, and hip.
Percentage of Participants With a Major Osteoporotic Fracture Through Month 24	24 Months	Major osteoporotic fractures included clinical vertebral fractures and fractures of the hip, forearm and humerus. Fractures associated with high trauma severity or pathologic fractures were excluded.
Percentage of Participants With Multiple New or Worsening Vertebral Fractures Through Month 12	12 Months	A new or worsening vertebral fracture was identified when there was a ≥ 1 grade increase from the previous grade in any vertebra from T4 to L4. A participant had multiple new or worsening vertebral fractures when there were ≥ 2 vertebrae from T4 to L4 with ≥ 1 grade increase from the previous grade. The multiple new or worsening vertebral fractures need not have occurred at the same visit.
Percentage of Participants With Multiple New or Worsening Vertebral Fractures Through Month 24	24 Months	A new or worsening vertebral fracture was identified when there was a ≥ 1 grade increase from the previous grade in any vertebra from T4 to L4. A participant had multiple new or worsening vertebral fractures when there were ≥ 2 vertebrae from T4 to L4 with ≥ 1 grade increase from the previous grade. The multiple new or worsening vertebral fractures need not have occurred at the same visit.
Percent Change From Baseline in Bone Mineral Density at the Lumbar Spine at Month 12	Baseline and Month 12	Bone mineral density (BMD) was measured by dual-energy x-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging center.
Percent Change From Baseline In Bone Mineral Density at the Lumbar Spine at Month 24	Baseline and Month 24	Bone mineral density (BMD) was measured by dual-energy x-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging center.
Percent Change From Baseline in Bone Mineral Density of the Total Hip at Month 12	Baseline and Month 12	Bone mineral density (BMD) was measured by dual-energy x-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging center.
Percent Change From Baseline in Bone Mineral Density of the Total Hip at Month 24	Baseline and Month 24	Bone mineral density (BMD) was measured by dual-energy x-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging center.
Percent Change From Baseline in Bone Mineral Density of the Femoral Neck at Month 12	Baseline and Month 12	Bone mineral density (BMD) was measured by dual-energy x-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging center.
Percent Change From Baseline in Bone Mineral Density of the Femoral Neck at Month 24	Baseline and Month 24	Bone mineral density (BMD) was measured by dual-energy x-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging center.