A Multi-Center, Randomized, Open-Label Study to Assess the Immunogenicity and Safety of Denosumab in Pre-filled Syringe Compared to Vial in Subjects With Low Bone Mineral Density

Study Overview
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Brief Summary
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The purpose of this study is to compare the immunogenicity profiles of denosumab pre-filled syringe (PFS) and vial at 6 months in postmenopausal women with low bone mineral density (BMD).

Official Title
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A Multi-Center, Randomized, Open-Label Study to Assess the Immunogenicity and Safety of Denosumab in Pre-filled Syringe Compared to Vial in Subjects With Low Bone Mineral Density

Conditions
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Low Bone Mineral Density, Osteopenia, Osteoporosis

Intervention / Treatment
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* Biological: denosumab
* Biological: denosumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients who have successfully completed the 20050141 study (NCT00330460): Must have received all SC investigational product administrations in 20050141 Must not have taken any proscribed therapies in 20050141 Subjects who were in the alendronate or denosumab treatment group are allowed Provide signed informed consent before any study-specific procedures are conducted Exclusion Criteria: Any disorder that, in the opinion of the investigator, may compromise the ability of the patient to give written informed consent and/or comply with study procedures including: Any physical or psychiatric disorder Or evidence of alcohol or substance abuse in the last 12 months Any clinical evidence, in the medical judgement of the investigator, of the following medical conditions: Impaired thyroid function (subsequent to treatment) Impaired hepatic function Impaired renal function Rheumatoid Arthritis, Paget's disease, Cushing's disease, hyperprolactinemia, or cirrhosis of the liver Known to have tested positive for human immunodeficiency virus, hepatitis C virus, or hepatitis B surface antigen Any metabolic bone disease, eg, osteomalacia or osteogenesis imperfecta, which may interfere with the interpretation of the findings

Ages Eligible for Study
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Minimum Age: 18 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: Denosumab - Vial<br>Participants received denosumab 60 mg subcutaneous injection using a standard vial on Day 1 and at Month 6. | Biological: denosumab<br>* 60 mg denosumab in 1mL<br>|
| Experimental: Denosumab - Prefilled syringe<br>Participants received denosumab 60 mg subcutaneous injection using a pre-filled syringe on Day 1 and at Month 6. | Biological: denosumab<br>* 60 mg denosumab in 1mL<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Who Tested Positive for Anti-denosumab Antibodies at Month 6 | An electrochemiluminescent bridging immunoassay was used to test blood samples for binding antibodies to denosumab. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Who Tested Positive for Anti-denosumab Antibodies at Month 12 | An electrochemiluminescent bridging immunoassay was used to test blood samples for binding antibodies to denosumab. | 12 months | 
| Number of Participants With Neutralizing Antibodies Against Denosumab at Month 12 | Samples demonstrating reactivity for binding antibodies to denosumab were to be tested for neutralizing or inhibitory effects in a cell-based bioassay. | Month 12 | 
| Sodium Change From Baseline at Month 1 | Laboratory chemistry sodium | Baseline, month 1 | 
| Sodium Change From Baseline at Month 6 | Laboratory chemistry sodium | Baseline, month 6 | 
| Sodium Change From Baseline at Month 12 | Sodium Change From Baseline at Month 12 | Baseline, Month 12 | 
| Potassium Change From Baseline at Month 1 | Laboratory chemistry potassium | Baseline, month 1 | 
| Potassium Change From Baseline at Month 6 | Laboratory chemistry potassium | Baseline, month 6 | 
| Potassium Change From Baseline at Month 12 | Laboratory chemistry potassium | Baseline, month 12 | 
| Chloride Change From Baseline at Month 1 | Laboratory chemistry chloride | Baseline, month 1 | 
| Chloride Change From Baseline at Month 6 | Laboratory chemistry chloride | Baseline, month 6 | 
| Chloride Change From Baseline at Month 12 | Laboratory chemistry chloride | Baseline, month 12 | 
| Bicarbonate Change From Baseline at Month 1 | Laboratory chemistry bicarbonate | Baseline, month 1 | 
| Bicarbonate Change From Baseline at Month 6 | Laboratory chemistry bicarbonate | Baseline, month 6 | 
| Bicarbonate Change From Baseline at Month 12 | Laboratory chemistry bicarbonate | Baseline, month 12 | 
| Magnesium Change From Baseline at Month 1 | Laboratory chemistry magnesium | Baseline, month 1 | 
| Magnesium Change From Baseline at Month 6 | Laboratory chemistry magnesium | Baseline, month 6 | 
| Magnesium Change From Baseline at Month 12 | Laboratory chemistry magnesium | Baseline, month 12 | 
| Blood Urea Nitrogen Change From Baseline at Month 1 | Laboratory chemistry blood urea nitrogen | Baseline, month 1 | 
| Blood Urea Nitrogen Change From Baseline at Month 6 | Laboratory chemistry blood urea nitrogen | Baseline, month 6 | 
| Blood Urea Nitrogen Change From Baseline at Month 12 | Laboratory chemistry blood urea nitrogen | Baseline, month 12 | 
| Creatinine Change From Baseline at Month 1 | Laboratory chemistry creatinine | Baseline, month 1 | 
| Creatinine Change From Baseline at Month 6 | Laboratory chemistry creatinine | Baseline, month 6 | 
| Creatinine Change From Baseline at Month 12 | Laboratory chemistry creatinine | Baseline, month 12 | 
| Aspartate Amino Transferase Change From Baseline at Month 1 | Laboratory chemistry aspartate amino transferase | Baseline, month 1 | 
| Aspartate Amino Transferase Change From Baseline at Month 6 | Laboratory chemistry aspartate amino transferase | Baseline, month 6 | 
| Aspartate Amino Transferase Change From Baseline at Month 12 | Laboratory chemistry aspartate amino transferase | Baseline, month 12 | 
| Alanine Amino Transferase Change From Baseline at Month 1 | Laboratory chemistry alanine amino transferase | Baseline, month 1 | 
| Alanine Amino Transferase Change From Baseline at Month 6 | Laboratory chemistry alanine amino transferase | Baseline, month 6 | 
| Alanine Amino Transferase Change From Baseline at Month 12 | Laboratory chemistry alanine amino transferase | Baseline, month 12 | 
| Total Bilirubin Change From Baseline at Month 1 | Laboratory chemistry total bilirubin | Baseline, month 1 | 
| Total Bilirubin Change From Baseline at Month 6 | Laboratory chemistry total bilirubin | Baseline, month 6 | 
| Total Bilirubin Change From Baseline at Month 12 | Laboratory chemistry total bilirubin | Baseline, month 12 | 
| Albumin Change From Baseline at Month 1 | Laboratory chemistry albumin | Baseline, month 1 | 
| Albumin Change From Baseline at Month 6 | Laboratory chemistry albumin | Baseline, month 6 | 
| Albumin Change From Baseline at Month 12 | Laboratory chemistry albumin | Baseline, month 12 | 
| Total Protein Change From Baseline at Month 1 | Laboratory chemistry total protein | Baseline, month 1 | 
| Total Protein Change From Baseline at Month 6 | Laboratory chemistry total protein | Baseline, month 6 | 
| Total Protein Change From Baseline at Month 12 | Laboratory chemistry total protein | Baseline, month 12 | 
| Glucose Change From Baseline at Month 1 | Laboratory chemistry glucose | Baseline, month 1 | 
| Glucose Change From Baseline at Month 6 | Laboratory chemistry glucose | Baseline, month 6 | 
| Glucose Change From Baseline at Month 12 | Laboratory chemistry glucose | Baseline, month 12 | 
| Red Blood Cells Change From Baseline at Month 1 | Laboratory hematology red blood cells | Baseline, month 1 | 
| Red Blood Cells Change From Baseline at Month 6 | Laboratory hematology red blood cells | Baseline, month 6 | 
| Red Blood Cells Change From Baseline at Month 12 | Laboratory hematology red blood cells | Baseline, month 12 | 
| Hemoglobin Change From Baseline at Month 1 | Laboratory hematology hemoglobin | Baseline, month 1 | 
| Hemoglobin Change From Baseline at Month 6 | Laboratory hematology hemoglobin | Baseline, month 6 | 
| Hemoglobin Change From Baseline at Month 12 | Laboratory hematology hemoglobin | Baseline, month 12 | 
| Reticulocytes Change From Baseline at Month 1 | Laboratory hematology reticulocytes | Baseline, month 1 | 
| Reticulocytes Change From Baseline at Month 6 | Laboratory hematology reticulocytes | Baseline, month 6 | 
| Reticulocytes Change From Baseline at Month 12 | Laboratory hematology reticulocytes | Baseline, month 12 | 
| Platelets Change From Baseline at Month 1 | Laboratory hematology platelets | Baseline, month 1 | 
| Platelets Change From Baseline at Month 6 | Laboratory hematology platelets | Baseline, month 6 | 
| Platelets Change From Baseline at Month 12 | Laboratory hematology platelets | Baseline, month 12 | 
| White Blood Cells Change From Baseline at Month 1 | Laboratory hematology white blood cells | Baseline, month 1 | 
| White Blood Cells Change From Baseline at Month 6 | Laboratory hematology white blood cells | Baseline, month 6 | 
| White Blood Cells Change From Baseline at Month 12 | Laboratory hematology white blood cells | Baseline, month 12 | 
| Total Neutrophils Change From Baseline at Month 1 | Laboratory hematology total neutrophils | Baseline, month 1 | 
| Total Neutrophils Change From Baseline at Month 6 | Laboratory hematology total neutrophils | Baseline, month 6 | 
| Total Neutrophils Change From Baseline at Month 12 | Laboratory hematology total neutrophils | Baseline, month 12 | 
| Eosinophils Change From Baseline at Month 1 | Laboratory hematology eosinophils | Baseline, month 1 | 
| Eosinophils Change From Baseline at Month 6 | Laboratory hematology eosinophils | Baseline, month 6 | 
| Eosinophils Change From Baseline at Month 12 | Laboratory hematology eosinophils | Baseline, month 12 | 
| Basophils Change From Baseline at Month 1 | Laboratory hematology basophils | Baseline, month 1 | 
| Basophils Change From Baseline at Month 6 | Laboratory hematology basophils | Baseline, month 6 | 
| Basophils Change From Baseline at Month 12 | Laboratory hematology basophils | Baseline, month 12 | 
| Lymphocytes Change From Baseline at Month 1 | Laboratory hematology lymphocytes | Baseline, month 1 | 
| Lymphocytes Change From Baseline at Month 6 | Laboratory hematology lymphocytes | Baseline, month 6 | 
| Lymphocytes Change From Baseline at Month 12 | Laboratory hematology lymphocytes | Baseline, month 12 | 
| Monocytes Change From Baseline at Month 1 | Laboratory hematology monocytes | Baseline, month 1 | 
| Monocytes Change From Baseline at Month 6 | Laboratory hematology monocytes | Baseline, month 6 | 
| Monocytes Change From Baseline at Month 12 | Laboratory hematology monocytes | Baseline, month 12 | 
| Number of Participants With Laboratory Toxicity CTCAE Grade Greater or Equal to 3 | Participants with laboratory toxicity grade 3 (severe) or 4 (life-threatening), based on the Common Terminology Criteria for Adverse Events (CTCAE), version 3.0. | Day 1 to Month 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Osteopenia, Osteoporosis, AMG 162, Postmenopausal, Pre-filled syringe