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

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).

Study Overview

• Status: Completed
• Conditions: Osteoporosis; Osteopenia; Low Bone Mineral Density
• Intervention / Treatment: Biological: denosumab

• Study Type: Interventional
• Enrollment (Actual): 311
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

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: Denosumab - Vial; Participants received denosumab 60 mg subcutaneous injection using a standard vial on Day 1 and at Month 6.	Biological: denosumab; 60 mg denosumab in 1mL
Experimental: Denosumab - Prefilled syringe; Participants received denosumab 60 mg subcutaneous injection using a pre-filled syringe on Day 1 and at Month 6.	Biological: denosumab; 60 mg denosumab in 1mL

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Amgen

Publications and helpful links

Helpful Links

• AmgenTrials clinical trials website
• Notice regarding posted summaries of trial results

Study record dates

Study Major Dates

• Study Start: May 1, 2007
• Primary Completion (Actual): March 1, 2008
• Study Completion (Actual): March 1, 2009

Study Registration Dates

• First Submitted: August 9, 2007
• First Submitted That Met QC Criteria: August 9, 2007
• First Posted (Estimate): August 13, 2007

Study Record Updates

• Last Update Posted (Estimate): October 31, 2013
• Last Update Submitted That Met QC Criteria: August 27, 2013
• Last Verified: August 1, 2013

More Information

Terms related to this study

• Keywords: Osteoporosis; Osteopenia; Postmenopausal; AMG 162; Pre-filled syringe
• Additional Relevant MeSH Terms: Metabolic Diseases; Musculoskeletal Diseases; Bone Diseases; Osteoporosis; Bone Diseases, Metabolic; Physiological Effects of Drugs; Bone Density Conservation Agents; Denosumab
• Other Study ID Numbers: 20060237