Efficacy and Safety of Romosozumab Treatment in Postmenopausal Women With Osteoporosis

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

Official Title
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A Multicenter, International, Randomized, Double-blind, Placebo-controlled, Parallel-group Study to Assess the Efficacy and Safety of Romosozumab Treatment in Postmenopausal Women With Osteoporosis

Conditions
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Postmenopausal Osteoporosis

Intervention / Treatment
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* Drug: Romosozumab
* Drug: Placebo
* Drug: Denosumab


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 55 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Romosozumab<br>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. | Drug: Romosozumab<br>* Administered by subcutaneous injection once a month (QM)<br>* Other names: EVENITY™;Drug: Denosumab<br>* Administered by subcutaneous injection once every 6 months (Q6M)<br>* Other names: Prolia®;|
| Placebo Comparator: Placebo<br>Participants received placebo subcutaneous injections once a month for 12 months, followed by 60 mg denosumab subcutaneously once every 6 months for 24 months. | Drug: Placebo<br>* Administered by subcutaneous injection once a month (QM)<br>Drug: Denosumab<br>* Administered by subcutaneous injection once every 6 months (Q6M)<br>* Other names: Prolia®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With New Vertebral Fracture Through Month 12 | 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. | 12 Months | 
| Percentage of Participants With New Vertebral Fracture Through Month 24 | 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. | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With a Clinical Fracture Through Month 12 | 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. | 12 Months | 
| Percentage of Participants With a Nonvertebral Fracture Through Month 12 | 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. | 12 Months | 
| Percentage of Participants With a Nonvertebral Fracture Through Month 24 | 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. | 24 Months | 
| Percentage of Participants With a Clinical Fracture Through Month 24 | 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. | 24 Months | 
| Percentage of Participants With a Major Nonvertebral Fracture Through Month 12 | 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. | 12 Months | 
| Percentage of Participants With a Major Nonvertebral Fracture Through Month 24 | 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. | 24 Months | 
| Percentage of Participants With a New or Worsening Vertebral Fracture Through Month 12 | 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. | 12 Months | 
| Percentage of Participants With a New or Worsening Vertebral Fracture Through Month 24 | 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. | 24 Months | 
| Percentage of Participants With a Hip Fracture Through Month 12 | Hip fractures were defined as a subset of nonvertebral fractures including fractures of the femur neck, femur intertrochanter, and femur subtrochanter. | 12 Months | 
| Percentage of Participants With a Hip Fracture Through Month 24 | Hip fractures were defined as a subset of nonvertebral fractures including fractures of the femur neck, femur intertrochanter, and femur subtrochanter. | 24 Months | 
| Percentage of Participants With a Major Osteoporotic Fracture Through Month 12 | 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. | 12 Months | 
| Percentage of Participants With a Major Osteoporotic Fracture Through Month 24 | 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. | 24 Months | 
| Percentage of Participants With Multiple New or Worsening Vertebral Fractures Through Month 12 | 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. | 12 Months | 
| Percentage of Participants With Multiple New or Worsening Vertebral Fractures Through Month 24 | 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. | 24 Months | 
| Percent Change From Baseline in Bone Mineral Density at the Lumbar Spine at Month 12 | Bone mineral density (BMD) was measured by dual-energy x-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging center. | Baseline and Month 12 | 
| Percent Change From Baseline In Bone Mineral Density at the Lumbar Spine at Month 24 | Bone mineral density (BMD) was measured by dual-energy x-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging center. | Baseline and Month 24 | 
| Percent Change From Baseline in Bone Mineral Density of the Total Hip at Month 12 | Bone mineral density (BMD) was measured by dual-energy x-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging center. | Baseline and Month 12 | 
| Percent Change From Baseline in Bone Mineral Density of the Total Hip at Month 24 | Bone mineral density (BMD) was measured by dual-energy x-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging center. | Baseline and Month 24 | 
| Percent Change From Baseline in Bone Mineral Density of the Femoral Neck at Month 12 | Bone mineral density (BMD) was measured by dual-energy x-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging center. | Baseline and Month 12 | 
| Percent Change From Baseline in Bone Mineral Density of the Femoral Neck at Month 24 | Bone mineral density (BMD) was measured by dual-energy x-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging center. | Baseline and Month 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Osteoporosis, Osteoporosis-Postmenopausal, Bone Diseases-Metabolic, Bone Diseases, Musculoskeletal Diseases