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

Phase 3

Completed

• Conditions: Osteopenia; Osteoporosis; Low Bone Mineral Density
• Interventions: Biological: denosumab

• Registration Number: NCT00515463
• Lead Sponsor: Amgen

Brief Summary

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).

Detailed Description

Not available

Study Timeline

• Study Start: 2007-05
• Study First Submitted: 2007-08-09
• Study First Submitted QC: 2007-08-09
• Study First Posted: 2007-08-13
• Primary Completion: 2008-03
• Study Completion: 2009-03
• Disposition First Submitted: 2009-11-23
• Disposition First Submitted QC: 2009-11-23
• Disposition First Posted: 2009-11-25
• Results First Submitted: 2010-06-18
• Status Verified: 2013-08
• Results First Submitted QC: 2013-08-27
• Last Update Submitted: 2013-08-27
• Results First Posted: 2013-10-31
• Last Update Posted: 2013-10-31

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 311

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Denosumab - Vial	denosumab	Participants received denosumab 60 mg subcutaneous injection using a standard vial on Day 1 and at Month 6.
Denosumab - Prefilled syringe	denosumab	Participants received denosumab 60 mg subcutaneous injection using a pre-filled syringe on Day 1 and at Month 6.

Primary Outcome Measures

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

Secondary Outcome Measures

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