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Completed

NCT Number: NCT01631214

Study to Determine the Efficacy and Safety of Romosozumab in the Treatment of Postmenopausal Women With Osteoporosis

The purpose of this study is to determine if treatment is effective in preventing fractures in women with postmenopausal osteoporosis.

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Key information

Conditions

Postmenopausal Women With Osteoporosis Bone Diseases Bone Diseases, Metabolic Metabolic Diseases Musculoskeletal Diseases Nutritional and Metabolic Diseases Osteoporosis Osteoporosis, Postmenopausal

Age range

55 year–90 year

Sex eligibility

Female

Study type

Interventional

Phase

Phase 3

Primary location

Research Site, Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Romosozumab

Biological

Romosozumab 210 mg administered by subcutaneous injection once a month during the double-blind treatment phase.

Other names: AMG 785, Evenity

Alendronate

Drug

Alendronate 70 mg tablet taken once a week

Other names: Fosamax

Placebo to Romosozumab

Drug

Administered by subcutaneous injection once a month during the double-blind treatment phase.

Placebo to Alendronate

Drug

Matching placebo tablet taken once a week during the double-blind treatment phase.

Primary outcomes

  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 outcomes

  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.

Sponsors and collaborators

Lead sponsor

Amgen

Industry

Registry information

Official study 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

Acronym: ARCH

Important dates

Study start
2012
Primary completion
2017
Study completion
2017
First posted
Jun 29, 2012
Registry last updated
Feb 21, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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