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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01575834
Recruitment Status : Completed
First Posted : April 12, 2012
Results First Posted : November 8, 2018
Last Update Posted : December 22, 2020
Sponsor:
Information provided by (Responsible Party):
Amgen

Tracking Information
First Submitted Date  ICMJE April 4, 2012
First Posted Date  ICMJE April 12, 2012
Results First Submitted Date  ICMJE September 24, 2018
Results First Posted Date  ICMJE November 8, 2018
Last Update Posted Date December 22, 2020
Actual Study Start Date  ICMJE March 15, 2012
Actual Primary Completion Date December 14, 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 11, 2018)
  • 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.
  • 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.
Original Primary Outcome Measures  ICMJE
 (submitted: April 10, 2012)
Incidence of vertebral fracture [ Time Frame: 12 Months ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 11, 2018)
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: April 10, 2012)
  • Incidence of Fracture [ Time Frame: 12 Months ]
  • Changes In Bone Mineral Density from Baseline to 12 Months [ Time Frame: 12 Months ]
  • Incidence of Fracture [ Time Frame: 24 Months ]
  • Changes In Bone Mineral Density from Baseline to 24 Months [ Time Frame: 24 Months ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Efficacy and Safety of Romosozumab Treatment in Postmenopausal Women With Osteoporosis
Official Title  ICMJE 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
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 Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Postmenopausal Osteoporosis
Intervention  ICMJE
  • Drug: Romosozumab
    Administered by subcutaneous injection once a month (QM)
    Other Names:
    • AMG 785
    • EVENITY™
  • Drug: Placebo
    Administered by subcutaneous injection once a month (QM)
  • Drug: Denosumab
    Administered by subcutaneous injection once every 6 months (Q6M)
    Other Name: Prolia®
Study Arms  ICMJE
  • 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.
    Interventions:
    • Drug: Romosozumab
    • Drug: Denosumab
  • 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.
    Interventions:
    • Drug: Placebo
    • Drug: Denosumab
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 3, 2014)
7180
Original Estimated Enrollment  ICMJE
 (submitted: April 10, 2012)
5600
Actual Study Completion Date  ICMJE December 28, 2016
Actual Primary Completion Date December 14, 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 55 Years to 90 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Argentina,   Australia,   Belgium,   Brazil,   Canada,   Colombia,   Czechia,   Denmark,   Dominican Republic,   Estonia,   Germany,   Hungary,   India,   Japan,   Latvia,   Lithuania,   Mexico,   New Zealand,   Poland,   Romania,   Spain,   Switzerland,   United Kingdom,   United States
Removed Location Countries Czech Republic,   Hong Kong
 
Administrative Information
NCT Number  ICMJE NCT01575834
Other Study ID Numbers  ICMJE 20070337
2011-001456-11 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Amgen
Study Sponsor  ICMJE Amgen
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: MD Amgen
PRS Account Amgen
Verification Date December 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP