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Trial record 1 of 1 for:    NCT01631214
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Study to Determine the Efficacy and Safety of Romosozumab in the Treatment of Postmenopausal Women With Osteoporosis (ARCH)

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: NCT01631214
Recruitment Status : Completed
First Posted : June 29, 2012
Results First Posted : December 12, 2018
Last Update Posted : November 8, 2022
Sponsor:
Information provided by (Responsible Party):
Amgen

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

Condition or disease Intervention/treatment Phase
Postmenopausal Women With Osteoporosis Biological: Romosozumab Drug: Alendronate Drug: Placebo to Romosozumab Drug: Placebo to Alendronate Phase 3

Detailed Description:

In this trial, women were randomly assigned in a 1:1 ratio to receive monthly subcutaneous romosozumab or weekly oral alendronate for 12 months. Randomization was stratified according to age (<75 vs. ≥75 years). After completion of the double-blind treatment period, all the participants were to receive open-label weekly oral alendronate until the end of the trial, with blinding to the initial treatment assignment maintained.

The primary analysis was performed when clinical fracture events had been confirmed in at least 330 participants and all the participants had completed the month 24 visit. The study was to continue in an event-driven manner until at least 440 participants experienced a nonvertebral fracture or if the superiority of romosozumab was proven for nonvertebral fractures at the primary analysis.

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 4093 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, Alendronate-controlled Study to Determine the Efficacy and Safety of Romosozumab in the Treatment of Postmenopausal Women With Osteoporosis
Actual Study Start Date : May 4, 2012
Actual Primary Completion Date : February 27, 2017
Actual Study Completion Date : June 29, 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Osteoporosis

Arms and Interventions
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Arm Intervention/treatment
Active Comparator: Alendronate/Alendronate
Participants received 70 mg alendronate once a week and placebo to romosozumab subcutaneously once a month for the first 12 months. After completion of the 12-month double-blind treatment period participants continued to receive 70 mg alendronate once a week until the end of the study.
 Drug: Alendronate
Alendronate 70 mg tablet taken once a week
Other Name: Fosamax

Drug: Placebo to Romosozumab
Administered by subcutaneous injection once a month during the double-blind treatment phase.
Experimental: Romosozumab/Alendronate
Participants received 210 mg romosozumab subcutaneously once a month and placebo to alendronate orally once a week for the first 12 months. After completion of the 12-month double-blind treatment period participants received 70 mg alendronate once a week until the end of the study.
 Biological: Romosozumab
Romosozumab 210 mg administered by subcutaneous injection once a month during the double-blind treatment phase.
Other Names:
  • AMG 785
  • Evenity

Drug: Alendronate
Alendronate 70 mg tablet taken once a week
Other Name: Fosamax

Drug: Placebo to Alendronate
Matching placebo tablet taken once a week during the double-blind treatment phase.


Outcome Measures
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Primary Outcome Measures :
  1. Percentage of Participants With New Vertebral Fractures Through Month 24 [ Time Frame: 24 months ]

    All fracture assessments were performed by blinded central imaging readers.

    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 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.

    Incident vertebral fractures were confirmed by a second independent reader using the Semiquantitative method.


  2. Percentage of Participants With a Clinical Fracture at the Primary Analysis [ Time Frame: The primary analysis was performed when clinical fracture events had been confirmed in at least 330 patients and all participants had completed the month 24 visit. The median follow-up was 2.7 years (interquartile range, 2.2 to 3.3). ]
    All fracture assessments were performed by blinded central imaging readers. 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.


Secondary Outcome Measures :
  1. Percentage of Participants With a Nonvertebral Fracture at the Primary Analysis [ Time Frame: The primary analysis was performed when clinical fracture events had been confirmed in at least 330 patients and all participants had completed the month 24 visit. The median follow-up was 2.7 years (interquartile range, 2.2 to 3.3). ]
    A nonvertebral fracture was defined as a documented fracture 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.

  2. Percentage of Participants With Any Fracture at the Primary Analysis [ Time Frame: The primary analysis was performed when clinical fracture events had been confirmed in at least 330 patients and all participants had completed the month 24 visit. The median follow-up was 2.7 years (interquartile range, 2.2 to 3.3). ]
    All fractures include any osteoporotic nonvertebral fractures that are not associated with high trauma severity or pathologic fractures and new or worsening vertebral fractures regardless of trauma severity or pathologic fractures.

  3. 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 according to the Genant Semiquantitative Scoring method 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.

    Incident vertebral fractures were confirmed by a second independent reader using the Semiquantitative method.


  4. Percentage of Participants With a Major Nonvertebral Fracture at the Primary Analysis [ Time Frame: The primary analysis was performed when clinical fracture events had been confirmed in at least 330 patients and all participants had completed the month 24 visit. The median follow-up was 2.7 years (interquartile range, 2.2 to 3.3). ]
    Major nonvertebral fractures included 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.

  5. Percentage of Participants With a Hip Fracture at the Primary Analysis [ Time Frame: The primary analysis was performed when clinical fracture events had been confirmed in at least 330 patients and all participants had completed the month 24 visit. The median follow-up was 2.7 years (interquartile range, 2.2 to 3.3). ]
    Hip fractures were defined as a subset of nonvertebral fractures including fractures of the femur neck, femur intertrochanter, and femur subtrochanter.

  6. 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 according to the Genant Semiquantitative Scoring method. 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. Incident vertebral fractures were confirmed by a second independent reader.

  7. 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.

  8. Percentage of Participants With a Nonvertebral Fracture Through Month 24 [ Time Frame: 24 months ]
    A nonvertebral fracture was defined as a documented fracture 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.

  9. 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.

  10. Percentage of Participants With a Clinical Vertebral Fracture Through Month 24 [ Time Frame: 24 months ]
    A clinical vertebral fracture is a new or worsening vertebral fracture assessed at either a scheduled or unscheduled visit and associated with any signs and/or symptoms of back pain indicative of a fracture, regardless of trauma severity or whether it is pathologic.

  11. 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.

  12. Percentage of Participants With New Vertebral Fractures 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 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.

    Incident vertebral fractures were confirmed by a second independent reader.


  13. Percentage of Participants With Any Fracture Through Month 12 [ Time Frame: 12 months ]
    All fractures include any osteoporotic nonvertebral fractures that are not associated with high trauma severity or pathologic fractures and new or worsening vertebral fractures regardless of trauma severity or pathologic fractures.

  14. 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.

  15. 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.

  16. 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.

  17. Percentage of Participants With a Clinical Vertebral Fracture Through Month 12 [ Time Frame: 12 months ]
    A clinical vertebral fracture is a new or worsening vertebral fracture assessed at either a scheduled or unscheduled visit and associated with any signs and/or symptoms of back pain indicative of a fracture, regardless of trauma severity or whether it is pathologic.

  18. 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.

  19. 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.

  20. Percent Change From Baseline in Bone Mineral Density of the Femoral Neck at 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.

  21. 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.

  22. Percent Change From Baseline in Bone Mineral Density at 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.

  23. Percent Change From Baseline in Bone Mineral Density at 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.

  24. Percent Change From Baseline in Bone Mineral Density of the Lumbar Spine at Month 36 [ Time Frame: Baseline and month 36 ]
    Bone mineral density (BMD) was measured by dual-energy x-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging center.

  25. Percent Change From Baseline in Bone Mineral Density of the Total Hip at Month 36 [ Time Frame: Baseline and month 36 ]
    Bone mineral density (BMD) was measured by dual-energy x-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging center.

  26. Percent Change From Baseline in Bone Mineral Density of the Femoral Neck at Month 36 [ Time Frame: Baseline and month 36 ]
    Bone mineral density (BMD) was measured by dual-energy x-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging center.


Eligibility Criteria
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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 who meet at least one of the following bone mineral density (BMD) and fracture criteria:

  • BMD T-score at the total hip or femoral neck of ≤ -2.50 and EITHER:

    • at least 1 moderate (semiquantitative grade [SQ]2) or severe (SQ3) vertebral fracture OR
    • at least 2 mild (SQ1) vertebral fractures OR

  • BMD T-score at the total hip or femoral neck of ≤ -2.00 and EITHER:

    • at least 2 moderate (SQ2) or severe (SQ3) vertebral fractures OR
    • a fracture of the proximal femur that occurred within 3 to 24 months prior to randomization.

Exclusion Criteria:

  • History of metabolic or bone disease (except osteoporosis)
  • Use of agents affecting bone metabolism
  • Vitamin D insufficiency
  • History of solid organ or bone marrow transplants
  • Hyper- or hypocalcemia
  • Hyper- or hypothyroidism
  • Hyper- or hypoparathyroidism
  • Possible signs of intolerance to alendronate
Contacts and Locations
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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): NCT01631214


Locations
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Sponsors and Collaborators
Amgen
Investigators
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Study Director: MD Amgen
  Study Documents (Full-Text)

Documents provided by Amgen:
Study Protocol  [PDF] September 14, 2016
Statistical Analysis Plan  [PDF] April 7, 2017

More Information
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Additional Information:

Publications:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT01631214    
Other Study ID Numbers: 20110142
2011-003142-41 ( EudraCT Number )
First Posted: June 29, 2012    Key Record Dates
Results First Posted: December 12, 2018
Last Update Posted: November 8, 2022
Last Verified: November 2022
Keywords provided by Amgen:
Osteoporosis, Osteoporosis-postmenopausal, Bone Diseases-Metabolic, Bone Diseases, Musculoskeletal Diseases
Additional relevant MeSH terms:
Layout table for MeSH terms
Osteoporosis
Bone Diseases, Metabolic
Bone Diseases
Musculoskeletal Diseases
Metabolic Diseases
 Alendronate
Antibodies, Monoclonal
Bone Density Conservation Agents
Physiological Effects of Drugs
Immunologic Factors