Transition From Alendronate to Romosozumab (AMG 785)

An Open-label, Randomized Study to Estimate the Percent Change From Baseline in Lumbar Spine Bone Mineral Density After 3 Months of AMG 785 Administration in Postmenopausal Women With Low Bone Mineral Density Previously Treated With Alendronate

The purpose of this study is to estimate the percent change from baseline in lumbar spine bone mineral density (BMD) following multiple-dose administrations of romosozumab in postmenopausal women with low BMD previously treated with alendronate.

Study Overview

• Status: Completed
• Conditions: Osteoporosis
• Intervention / Treatment: Drug: Romosozumab

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tucson, Arizona, United States, 85711
      • Research Site
  • California
    • Walnut Creek, California, United States, 94598
      • Research Site
  • Georgia
    • Gainesville, Georgia, United States, 30501
      • Research Site
  • Hawaii
    • Honolulu, Hawaii, United States, 96813
      • Research Site
  • Maryland
    • Bethesda, Maryland, United States, 20817
      • Research Site
  • New Mexico
    • Albuquerque, New Mexico, United States, 87106
      • Research Site
  • New York
    • West Haverstraw, New York, United States, 10993
      • Research Site
  • Pennsylvania
    • Wyomissing, Pennsylvania, United States, 19610
      • Research Site
  • Washington
    • Seattle, Washington, United States, 98144
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 55 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Postmenopausal women, defined as no vaginal bleeding or spotting for ≥ 12 months
• Low bone mineral density at screening [defined by a bone mineral density (BMD) T-score ≤ -2.0 and ≥ -4.0 at the lumbar spine (L1 to L4; or BMD T-score of evaluable vertebrae), total hip, or femoral neck]
• Currently taking alendronate (70 mg weekly or equivalent) exclusively for ≥ 1 year with verbal agreement that the subject has taken ≥ 80% of their doses with good tolerance

Exclusion Criteria:

• History of vertebral fracture, or fragility fracture of the wrist, humerus, hip or pelvis after age 50; or recent bone fracture within 6 months prior to screening
• History of metabolic or bone disease such as Paget's disease, rheumatoid arthritis, osteomalacia, osteogenesis imperfecta, osteopetrosis, ankylosing spondylitis, Cushing's disease, hyperprolactinemia, and malabsorption syndrome
• Vitamin D deficiency (defined as 25-OH-VitD levels < 20 ng/mL)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Romosozumab 140 mg; Participants received romosozumab 140 mg administered subcutaneously once a month for 3 months.	Drug: Romosozumab; Administered by subcutaneous injection; Other Names: AMG 785; EVENITY™
Experimental: Romosozumab 210 mg; Participants received romosozumab 210 mg administered subcutaneously once a month for 3 months.	Drug: Romosozumab; Administered by subcutaneous injection; Other Names: AMG 785; EVENITY™

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change From Baseline in Bone Mineral Density (BMD) at the Lumbar Spine	Bone mineral density was assessed by dual energy X-ray absorptiometry (DXA) scans of the lumbar spine (L1-L4) and analyzed by a central imaging lab.	Baseline and day 85

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change From Baseline in Bone Mineral Density (BMD) at the Femoral Neck	Bone mineral density was assessed by dual energy X-ray absorptiometry (DXA) scans and analyzed by a central imaging lab.	Baseline and day 85
Percent Change From Baseline in Bone Mineral Density (BMD) at the Total Hip	Bone mineral density was assessed by dual energy X-ray absorptiometry (DXA) scans and analyzed by a central imaging lab.	Baseline and day 85
Percent Change From Baseline in Serum Type-1 Aminoterminal Propeptide (P1NP)		Baseline and days 4, 15, 29, 43, 57, 71, and 85
Percent Change From Baseline in Serum C-telopeptide (sCTX)		Baseline and days 4, 15, 29, 43, 57, 71, and 85
Number of Participants With Adverse Events	An adverse event (AE) was defined as any untoward medical occurrence in a clinical trial participant. Laboratory value changes that required treatment or adjustment in current therapy were considered adverse events. A treatment-related adverse event (TRAE) was an adverse event assessed by the investigator as possibly related to the investigational product, indicated by a "yes" response to the question: Is there a reasonable possibility that the event may have been caused by the investigational product? A serious adverse event was defined as an adverse event that met at least 1 of the following serious criteria: fatal,; life-threatening,; required in-patient hospitalization or prolongation of existing hospitalization,; resulted in persistent or significant disability/incapacity,; congenital anomaly/birth defect, and/or; other medically important serious event.	From first dose of study drug up to day 85
Number of Participants Who Developed Anti-romosozumab Antibodies	Two validated assays were used to detect the presence of anti-romosozumab antibodies. An electrochemiluminescent bridging immunoassay was used to detect binding antibodies (screening assay) and confirm antibodies (confirmatory assay) capable of binding romosozumab. Samples testing positive in the immunoassay were further tested in a competitive binding bioassay for neutralizing activity against romosozumab. If a sample was positive for binding antibodies and demonstrated neutralizing activity, the participant was defined as positive for neutralizing antibodies. Participants who developed anti-romosozumab antibodies were those with a negative result at baseline and a positive result at any time postbaseline.	Baseline and days 29, 57, and 85
Mean Serum Concentration of Romosozumab		Days 4, 15, 29, 43, 57, 71 and 85

Collaborators and Investigators

• Sponsor: Amgen

Publications and helpful links

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start (Actual): March 30, 2012
• Primary Completion (Actual): November 21, 2012
• Study Completion (Actual): November 21, 2012

Study Registration Dates

• First Submitted: April 17, 2012
• First Submitted That Met QC Criteria: April 27, 2012
• First Posted (Estimate): May 1, 2012

Study Record Updates

• Last Update Posted (Actual): March 26, 2019
• Last Update Submitted That Met QC Criteria: March 12, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Keywords: AMG 785, bone mineral density, alendronate
• Additional Relevant MeSH Terms: Metabolic Diseases; Musculoskeletal Diseases; Bone Diseases; Bone Diseases, Metabolic; Osteoporosis
• Other Study ID Numbers: 20110253