Determine the Efficacy, Safety and Tolerability of Denosumab (AMG 162) in the Treatment of Postmenopausal Women With Low Bone Mineral Density

Study Overview
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Brief Summary
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To determine the effect of denosumab treatment compared with placebo over 12 months on bone mineral density (BMD) of the lumbar spine in postmenopausal women with low BMD. The clinical hypothesis is that denosumab subcutaneous injections administered every 3 or 6 months for 12 months will significantly increase lumbar spine bone mineral density and will be well tolerated.

Official Title
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A Randomized, Double-Blind, Placebo-controlled, Multi-dose Phase 2 Study to Determine the Efficacy, Safety and Tolerability of AMG 162 in the Treatment of Postmenopausal Women With Low Bone Mineral Density

Conditions
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Low Bone Mineral Density

Intervention / Treatment
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* Drug: Placebo
* Drug: Denosumab
* Drug: Alendronate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria women not more than 80 years of age on date of randomization ≥ 1 year postmenopausal on date of randomization ambulatory if ≤ 60 years of age, or had or would require a bilateral oophorectomy, serum follicle stimulating hormone (FSH) > 50 mU/mL or serum estradiol < 20 pg/mL low BMD (BMD T-score ≤ -1.8 at any 1 of the following sites: lumbar spine, femoral neck, or total hip; BMD T-scores must not have been < -4.0 at the lumbar spine or - 3.5 at the femoral neck or total hip) before any study-specific procedure, including the screening dual X-ray absorptiometry (DXA) scan, gave informed consent for participation in the study. Exclusion Criteria fluoride treatment for osteoporosis within the 2 years before the enrollment date bisphosphonate use within the 12 months before the enrollment date administration of the following medications within the 6 months before the enrollment date tibolone Parathyroid hormone (PTH) (or any derivative) systemic glucocorticosteroids (> 5 mg oral prednisone equivalent per day for > 10 days) inhaled corticosteroids (> 2000 μg per day for > 10 days) anabolic steroids or testosterone administration of the following medications within the 3 months before the enrollment date systemic hormone replacement therapy selective estrogen receptor modulators calcitonin calcitriol current hyper- or hypothyroidism (allowed if stable on thyroid replacement therapy and thyroid-stimulating hormone was within the normal range) current hyper- or hypoparathyroidism albumin-adjusted serum calcium < 8.5 mg/dL (< 2.125 mol/L) osteomalacia rheumatoid arthritis Paget's disease malignancy within the 5 years before enrollment (except cervical carcinoma in situ or basal cell carcinoma, which were acceptable) renal disease; ie, creatinine clearance ≤ 35 mL/min any bone disease, other than osteoporosis, which could interfere with the interpretation of the findings (eg, osteogenesis imperfecta or osteopetrosis) malabsorption syndrome weight, height, or girth that could preclude accurate DXA measurements < 2 lumbar vertebrae (L1 through L4) evaluable by DXA recent long bone fracture (within 6 months) osteoporotic-related fracture (ie, crush or wedge vertebral fracture or hip fracture) known or suspected to have occurred within 2 years of randomization > 1 single, grade 1 vertebral fracture currently enrolled in or had participated within the previous 30 days in other investigational device or drug trial(s) (For some trials, this may have been allowed after discussion and written approval from Amgen.) known sensitivity to mammalian-derived drug preparations (eg, Herceptin®) any organic or psychiatric disorder, serum chemistry, or hematology that, in the opinion of the investigator, could have prevented the subject from completing the study or have interfered with the interpretation of the study results self-reported alcohol or drug abuse within the previous 12 months any disorder that compromised the ability to give truly informed consent for participation in the study previous administration of denosumab known sensitivity or contraindication to alendronate known sensitivity or contraindication to tetracycline derivatives (subjects in the biopsy substudy only).

Ages Eligible for Study
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Maximum Age: 80 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Participants received double-blind subcutaneous (SC) placebo injections every 3 months until month 21 and then placebo SC injections once every 6 months from Month 24 through Month 42. | Drug: Placebo<br>* Placebo subcutaneous injection<br>|
| Experimental: Denosumab 6 mg every 3 months<br>Participants received denosumab 6 mg SC every 3 months until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. | Drug: Denosumab<br>* Denosumab for subcutaneous injection<br>* Other names: Prolia;|
| Experimental: Denosumab 14 mg every 3 months<br>Participants received denosumab 14 mg SC every 3 months until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. | Drug: Denosumab<br>* Denosumab for subcutaneous injection<br>* Other names: Prolia;|
| Experimental: Denosumab 30 mg every 3 months<br>Participants received denosumab 30 mg SC every 3 months until Month 21 then placebo SC every 6 months at Month 24 and Month 30 and then denosumab 60 mg SC every 6 months at Month 36 and Month 42. | Drug: Denosumab<br>* Denosumab for subcutaneous injection<br>* Other names: Prolia;|
| Experimental: Denosumab 14 mg every 6 months<br>Participants received denosumab 14 mg SC every 6 months until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. | Drug: Denosumab<br>* Denosumab for subcutaneous injection<br>* Other names: Prolia;|
| Experimental: Denosumab 60 mg every 6 months<br>Participants received denosumab 60 mg SC every 6 months until Month 42. | Drug: Denosumab<br>* Denosumab for subcutaneous injection<br>* Other names: Prolia;|
| Experimental: Denosumab 100 mg every 6 months<br>Participants received denosumab 100 mg SC every 6 months until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. | Drug: Denosumab<br>* Denosumab for subcutaneous injection<br>* Other names: Prolia;|
| Experimental: Denosumab 210 mg every 6 months<br>Participants received denosumab 210 mg SC every 6 months until Month 21 and then placebo every 6 months from Month 24 through Month 42. | Drug: Denosumab<br>* Denosumab for subcutaneous injection<br>* Other names: Prolia;|
| Active Comparator: Alendronate 70 mg<br>Participants received open-label alendronate 70 mg tablets orally once a week through Month 24. From Month 24 to Month 48 participants received no treatment. | Drug: Alendronate<br>* Alendronate 70 mg tablets<br>* Other names: Fosamax;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 12 for the Placebo and Denosumab Arms | Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 12 calculated using ((Month 12 value - Baseline value) / Baseline value ) x 100. | Baseline and Month 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum CTX Percent Change From Baseline at Month 12 | Serum C-Telopeptide (CTX). Percent change from Baseline to Month 12 calculated using ((Month 12 value - Baseline value) / Baseline value ) x 100. | Baseline and Month 12 | 
| Urine NTX/Creatinine Percent Change From Baseline at Month 12 | Urinary N-telopeptide (uNTX)/Creatinine. Percent change from Baseline to Month 12 calculated using ((Month 12 value - Baseline value) / Baseline value ) x 100. | Baseline and Month 12 | 
| Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 12 for the Alendronate Arm | Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 12 calculated using ((Month 12 value - Baseline value) / Baseline value ) x 100. | Baseline and Month 12 | 
| Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 24 | Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 24 calculated using ((Month 24 value - Baseline value) / Baseline value ) x 100. | Baseline and 24 months | 
| Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 36 | Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 36 calculated using ((Month 36 value - Baseline value) / Baseline value ) x 100. | Baseline and 36 months | 
| Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 42 | Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 42 calculated using ((Month 42 value - Baseline value) / Baseline value ) x 100. | Baseline and 42 months | 
| Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 48 | Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 48 calculated using ((Month 48 value - Baseline value) / Baseline value ) x 100. | Baseline and 48 months | 
| Serum CTX Percent Change From Baseline at Month 24 | Serum C-Telopeptide (CTX). Percent change from Baseline to Month 24 calculated using ((Month 24 value - Baseline value) / Baseline value ) x 100. | Baseline and 24 months | 
| Serum CTX Percent Change From Baseline at Month 36 | Serum C-Telopeptide (CTX). Percent change from Baseline to Month 36 calculated using ((Month 36 value - Baseline value) / Baseline value ) x 100. | Baseline and 36 months | 
| Serum CTX Percent Change From Baseline at Month 42 | Serum C-Telopeptide (CTX). Percent change from Baseline to Month 42 calculated using ((Month 42 value - Baseline value) / Baseline value ) x 100. | Baseline and 42 months | 
| Serum CTX Percent Change From Baseline at Month 48 | Serum C-Telopeptide (CTX). Percent change from Baseline to Month 48 calculated using ((Month 48 value - Baseline value) / Baseline value ) x 100. | Baseline and 48 months | 
| Urine NTX/Creatinine Percent Change From Baseline at Month 24 | Urinary N-telopeptide (uNTX)/Creatinine. Percent change from Baseline to Month 24 calculated using ((Month 24 value - Baseline value) / Baseline value ) x 100. | Baseline and 24 months | 
| Urine NTX/Creatinine Percent Change From Baseline at Month 36 | Urinary N-telopeptide (uNTX)/Creatinine. Percent change from Baseline to Month 36 calculated using ((Month 36 value - Baseline value) / Baseline value ) x 100. | Baseline and 36 months | 
| Urine NTX/Creatinine Percent Change From Baseline at Month 42 | Urinary N-telopeptide (uNTX)/Creatinine. Percent change from Baseline to Month 42 calculated using ((Month 42 value - Baseline value) / Baseline value ) x 100. | Baseline and 42 months | 
| Urine NTX/Creatinine Percent Change From Baseline at Month 48 | Urinary N-telopeptide (uNTX)/Creatinine. Percent change from Baseline to Month 48 calculated using ((Month 48 value - Baseline value) / Baseline value ) x 100. | Baseline and 48 months | 
| Total Hip Bone Mineral Density Percent Change From Baseline at Month 12 | Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 12 calculated using ((Month 12 value - Baseline value) / Baseline value ) x 100. | Baseline and 12 months | 
| Total Hip Bone Mineral Density Percent Change From Baseline at Month 24 | Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 24 calculated using ((Month 24 value - Baseline value) / Baseline value ) x 100. | Baseline and 24 months | 
| Total Hip Bone Mineral Density Percent Change From Baseline at Month 36 | Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 36 calculated using ((Month 36 value - Baseline value) / Baseline value ) x 100. | Baseline and 36 months | 
| Total Hip Bone Mineral Density Percent Change From Baseline at Month 42 | Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 42 calculated using ((Month 42 value - Baseline value) / Baseline value ) x 100. | Baseline and 42 months | 
| Total Hip Bone Mineral Density Percent Change From Baseline at Month 48 | Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 48 calculated using ((Month 48 value - Baseline value) / Baseline value ) x 100. | Baseline and 48 months | 
| Distal 1/3 Radius Bone Mineral Density Percent Change From Baseline at Month 12 | Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 12 calculated using ((Month 12 value - Baseline value) / Baseline value ) x 100. | Baseline and 12 months | 
| Distal 1/3 Radius Bone Mineral Density Percent Change From Baseline at Month 24 | Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 24 calculated using ((Month 24 value - Baseline value) / Baseline value ) x 100. | Baseline and 24 months | 
| Distal 1/3 Radius Bone Mineral Density Percent Change From Baseline at Month 36 | Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 36 calculated using ((Month 36 value - Baseline value) / Baseline value ) x 100. | Baseline and 36 months | 
| Distal 1/3 Radius Bone Mineral Density Percent Change From Baseline at Month 42 | Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 42 calculated using ((Month 42 value - Baseline value) / Baseline value ) x 100. | Baseline and 42 months | 
| Distal 1/3 Radius Bone Mineral Density Percent Change From Baseline at Month 48 | Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 48 calculated using ((Month 48 value - Baseline value) / Baseline value ) x 100. | Baseline and 48 months | 
| Total Body Bone Mineral Density Percent Change From Baseline at Month 12 | Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 12 calculated using ((Month 12 value - Baseline value) / Baseline value ) x 100. | Baseline and 12 months | 
| Total Body Bone Mineral Density Percent Change From Baseline at Month 24 | Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 24 calculated using ((Month 24 value - Baseline value) / Baseline value ) x 100. | Baseline and 24 months | 
| Total Body Bone Mineral Density Percent Change From Baseline at Month 36 | Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 36 calculated using ((Month 36 value - Baseline value) / Baseline value ) x 100. | Baseline and 36 months | 
| Total Body Bone Mineral Density Percent Change From Baseline at Month 42 | Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 42 calculated using ((Month 42 value - Baseline value) / Baseline value ) x 100. | Baseline and 42 months | 
| Total Body Bone Mineral Density Percent Change From Baseline at Month 48 | Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 48 calculated using ((Month 48 value - Baseline value) / Baseline value ) x 100. | Baseline and 48 months | 
| Bone Specific Alkaline Phosphatase Percent Change From Baseline at Month 12 | Bone specific alkaline phosphatase (BSAP). Percent change from Baseline to Month 12 calculated using ((Month 12 value - Baseline value) / Baseline value ) x 100. | Baseline and 12 months | 
| Bone Specific Alkaline Phosphatase Percent Change From Baseline at Month 24 | Bone specific alkaline phosphatase (BSAP). Percent change from Baseline to Month 24 calculated using ((Month 24 value - Baseline value) / Baseline value ) x 100. | Baseline and 24 months | 
| Bone Specific Alkaline Phosphatase Percent Change From Baseline at Month 36 | Bone specific alkaline phosphatase (BSAP). Percent change from Baseline to Month 36 calculated using ((Month 36 value - Baseline value) / Baseline value ) x 100. | Baseline and 36 months | 
| Bone Specific Alkaline Phosphatase Percent Change From Baseline at Month 42 | Bone specific alkaline phosphatase (BSAP). Percent change from Baseline to Month 42 calculated using ((Month 42 value - Baseline value) / Baseline value ) x 100. | Baseline and 42 months | 
| Bone Specific Alkaline Phosphatase Percent Change From Baseline at Month 48 | Bone specific alkaline phosphatase (BSAP). Percent change from Baseline to Month 48 calculated using ((Month 48 value - Baseline value) / Baseline value ) x 100. | Baseline and 48 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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bone loss, osteoporosis