Transition From Alendronate to Romosozumab (AMG 785)

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Osteoporosis

Intervention / Treatment
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* Drug: Romosozumab


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 55 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Romosozumab 140 mg<br>Participants received romosozumab 140 mg administered subcutaneously once a month for 3 months. | Drug: Romosozumab<br>* Administered by subcutaneous injection<br>* Other names: EVENITY™;|
| Experimental: Romosozumab 210 mg<br>Participants received romosozumab 210 mg administered subcutaneously once a month for 3 months. | Drug: Romosozumab<br>* Administered by subcutaneous injection<br>* Other names: EVENITY™;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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AMG 785, bone mineral density, alendronate