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Efficacy and Safety of Romosozumab Treatment in Postmenopausal Women With Osteoporosis (FRAME)

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ClinicalTrials.gov Identifier: NCT01575834
Recruitment Status : Completed
First Posted : April 12, 2012
Results First Posted : November 8, 2018
Last Update Posted : November 8, 2018
Sponsor:
Information provided by (Responsible Party):
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

Condition or disease Intervention/treatment Phase
Postmenopausal Osteoporosis Drug: Romosozumab Drug: Placebo Drug: Denosumab Phase 3

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 7180 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : March 15, 2012
Actual Primary Completion Date : December 14, 2015
Actual Study Completion Date : December 28, 2016

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Osteoporosis
Drug Information available for: Denosumab

Arm Intervention/treatment
Experimental: 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.
Drug: Romosozumab
Administered by subcutaneous injection once a month (QM)
Other Names:
  • AMG 785
  • EVENITY™

Drug: Denosumab
Administered by subcutaneous injection once every 6 months (Q6M)
Other Name: Prolia®

Placebo Comparator: 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.
Drug: Placebo
Administered by subcutaneous injection once a month (QM)

Drug: Denosumab
Administered by subcutaneous injection once every 6 months (Q6M)
Other Name: Prolia®




Primary Outcome Measures :
  1. Percentage of Participants With New Vertebral Fracture Through Month 12 [ Time Frame: 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.

  2. Percentage of Participants With New Vertebral Fracture Through Month 24 [ Time Frame: 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 :
  1. Percentage of Participants With a Clinical Fracture Through Month 12 [ Time Frame: 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.

  2. Percentage of Participants With a Nonvertebral Fracture Through Month 12 [ Time Frame: 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.

  3. Percentage of Participants With a Nonvertebral Fracture Through Month 24 [ Time Frame: 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.

  4. Percentage of Participants With a Clinical Fracture Through Month 24 [ Time Frame: 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.

  5. Percentage of Participants With a Major Nonvertebral Fracture Through Month 12 [ Time Frame: 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.

  6. Percentage of Participants With a Major Nonvertebral Fracture Through Month 24 [ Time Frame: 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.

  7. Percentage of Participants With a New or Worsening Vertebral Fracture Through Month 12 [ Time Frame: 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.

  8. Percentage of Participants With a New or Worsening Vertebral Fracture Through Month 24 [ Time Frame: 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.

  9. Percentage of Participants With a Hip Fracture Through Month 12 [ Time Frame: 12 Months ]
    Hip fractures were defined as a subset of nonvertebral fractures including fractures of the femur neck, femur intertrochanter, and femur subtrochanter.

  10. Percentage of Participants With a Hip Fracture Through Month 24 [ Time Frame: 24 Months ]
    Hip fractures were defined as a subset of nonvertebral fractures including fractures of the femur neck, femur intertrochanter, and femur subtrochanter.

  11. Percentage of Participants With a Major Osteoporotic Fracture Through Month 12 [ Time Frame: 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.

  12. Percentage of Participants With a Major Osteoporotic Fracture Through Month 24 [ Time Frame: 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.

  13. Percentage of Participants With Multiple New or Worsening Vertebral Fractures Through Month 12 [ Time Frame: 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.

  14. Percentage of Participants With Multiple New or Worsening Vertebral Fractures Through Month 24 [ Time Frame: 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.

  15. Percent Change From Baseline in Bone Mineral Density at the Lumbar Spine at Month 12 [ Time Frame: 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.

  16. Percent Change From Baseline In Bone Mineral Density at the Lumbar Spine at Month 24 [ Time Frame: 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.

  17. Percent Change From Baseline in Bone Mineral Density of the Total Hip at Month 12 [ Time Frame: 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.

  18. Percent Change From Baseline in Bone Mineral Density of the Total Hip at Month 24 [ Time Frame: 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.

  19. Percent Change From Baseline in Bone Mineral Density of the Femoral Neck at Month 12 [ Time Frame: 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.

  20. Percent Change From Baseline in Bone Mineral Density of the Femoral Neck at Month 24 [ Time Frame: 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.



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Ages Eligible for Study:   55 Years to 90 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01575834


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Sponsors and Collaborators
Amgen
Investigators
Study Director: MD Amgen

Additional Information:
Publications:
Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT01575834     History of Changes
Other Study ID Numbers: 20070337
2011-001456-11 ( EudraCT Number )
First Posted: April 12, 2012    Key Record Dates
Results First Posted: November 8, 2018
Last Update Posted: November 8, 2018
Last Verified: September 2018

Keywords provided by Amgen:
Osteoporosis, Osteoporosis-Postmenopausal, Bone Diseases-Metabolic, Bone Diseases, Musculoskeletal Diseases

Additional relevant MeSH terms:
Osteoporosis
Osteoporosis, Postmenopausal
Bone Diseases, Metabolic
Bone Diseases
Musculoskeletal Diseases
Metabolic Diseases
Denosumab
Bone Density Conservation Agents
Physiological Effects of Drugs