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Efficacy, Safety and Tolerability of Denosumab in the Treatment of Rheumatoid Arthritis

Primary Purpose

Rheumatoid Arthritis

Status
Completed
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
placebo
denosumab
Sponsored by
Amgen
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Rheumatoid Arthritis focused on measuring arthritis, joint pain, Methotrexate

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Diagnosis of RA. All subjects will be required to have been taking a stable dose of methotrexate. Active RA at screening defined as greater than or equal to 6 swollen joints. The presence of erosive disease Exclusion Criteria: Received any biologic agent (e.g., Enbrel®, Remicade®, Humira®, Kineret®) or Arava® within 8 weeks before randomization; past use of these agents is allowed. Steroid use greater than 15 mg/day. Scheduled for surgery or joint replacement in the hands, wrists or feet.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm 3

    Arm Type

    Experimental

    Experimental

    Placebo Comparator

    Arm Label

    Denosumab 180 mg

    Denosumab 60 mg

    Placebo

    Arm Description

    Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.

    Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.

    Participants received placebo subcutaneous injections on Day 1 and at Month 6.

    Outcomes

    Primary Outcome Measures

    Change From Baseline in Rheumatoid Arthritis Erosion Score Measured From MRI Assessments (RA-MRI ES) at Month 6
    Fifteen sites in each wrist and 10 sites in each hand were assessed by a blinded and independent reader. Each site was scored from 0 to 10 (in accordance with the European League Against Rheumatism [EULAR]-Outcome Measures in Rheumatology Clinical Trials convention), with each unit increment representing 10% incremental loss of the peripheral 1 cm of articular bone. The Erosion Score is a sum of erosion scores from 50 joint sites in both hands/wrists and ranges from 0 (normal, no erosion) to 500 (worst possible erosion).

    Secondary Outcome Measures

    Change From Baseline in Radiographic Total Modified Sharp Score (TSS) at Month 12
    TSS is the sum of erosion and joint space narrowing scores obtained from radiographs of the hands and feet, assessed by 2 independent readers. The joint erosion score is a summary of erosion severity in 32 joints of the hands and 12 joints in the feet. Each joint was scored, according to the surface area involved, from 0 (no erosion) to 5 (extensive loss of bone from more than one half of the articulating bone). Because each side of a foot joint was graded on this scale, the maximum erosion score for a foot joint was 10 and the maximal erosion score was 280. Joint Space Narrowing (JSN) Score summarizes the severity of JSN in 30 joints of the hands and 12 joints of the feet. Assessment of JSN for each hand (15 joints per hand) and foot (6 joints per foot), including subluxation, was scored from 0 (normal JSN) to 4 (complete loss of joint space, bony ankylosis, or luxation), with a maximum JSN score of 168. The TSS ranged from 0 (normal) to 448 (worst).
    Change From Baseline in Radiographic Total Modified Sharp Score (TSS) at Month 6
    TSS is the sum of erosion and joint space narrowing scores obtained from radiographs of the hands and feet, assessed by 2 independent readers. The joint erosion score is a summary of erosion severity in 32 joints of the hands and 12 joints in the feet. Each joint was scored, according to the surface area involved, from 0 (no erosion) to 5 (extensive loss of bone from more than one half of the articulating bone). Because each side of a foot joint was graded on this scale, the maximum erosion score for a foot joint was 10 and the maximal erosion score was 280. Joint Space Narrowing (JSN) Score summarizes the severity of JSN in 30 joints of the hands and 12 joints of the feet. Assessment of JSN for each hand (15 joints per hand) and foot (6 joints per foot), including subluxation, was scored from 0 (normal JSN) to 4 (complete loss of joint space, bony ankylosis, or luxation), with a maximum JSN score of 168. The TSS ranged from 0 (normal) to 448 (worst).
    Change From Baseline in Radiographic Erosion Score at Month 12
    The joint erosion score is a summary of erosion severity in 32 joints of the hands and 12 joints in the feet, obtained from radiographs of the hands and feet and assessed by 2 independent readers. Each joint was scored, according to the surface area involved, from 0 (no erosion) to 5 (extensive loss of bone from more than one half of the articulating bone). Because each side of a foot joint was graded on this scale, the maximum erosion score for a foot joint was 10 and the maximal erosion score was 280.
    Change From Baseline in Radiographic Erosion Score at Month 6
    The joint erosion score is a summary of erosion severity in 32 joints of the hands and 12 joints in the feet, obtained from radiographs of the hands and feet and assessed by 2 independent readers. Each joint was scored, according to the surface area involved, from 0 (no erosion) to 5 (extensive loss of bone from more than one half of the articulating bone). Because each side of a foot joint was graded on this scale, the maximum erosion score for a foot joint was 10 and the maximal erosion score was 280.
    Change From Baseline in Radiographic Joint Space Narrowing Score at Month 12
    Joint Space Narrowing (JSN) Score summarizes the severity of JSN in 30 joints of the hands and 12 joints of the feet obtained from radiographs of the hands and feet and assessed by 2 independent readers. Assessment of JSN for each hand (15 joints per hand) and foot (6 joints per foot), including subluxation, was scored from 0 (normal JSN) to 4 (complete loss of joint space, bony ankylosis, or luxation), with a maximum JSN score (indicating worst joint space narrowing) of 168.
    Change From Baseline in Radiographic Joint Space Narrowing Score at Month 6
    Joint Space Narrowing (JSN) Score summarizes the severity of JSN in 30 joints of the hands and 12 joints of the feet obtained from radiographs of the hands and feet and assessed by 2 independent readers. Assessment of JSN for each hand (15 joints per hand) and foot (6 joints per foot), including subluxation, was scored from 0 (normal JSN) to 4 (complete loss of joint space, bony ankylosis, or luxation), with a maximum JSN score (indicating worst joint space narrowing) of 168.
    Percent Change From Baseline in Lumbar Spine Bone Mineral Density at Month 1
    Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from baseline to Month 1 calculated using ((month 1 value - baseline value) / baseline value ) x 100. Least squares means are based on a repeated measures model adjusting for treatment, visit, baseline value, and strata (4 strata from the combination of baseline use of steroid and previous use of biologic).
    Percent Change From Baseline in Lumbar Spine Bone Mineral Density at Month 6
    Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from baseline to month 6 calculated using ((month 6 value - baseline value) / baseline value ) x 100. Least squares means are based on a repeated measures model adjusting for treatment, visit, baseline value, and strata (4 strata from the combination of baseline use of steroid and previous use of biologic).
    Percent Change From Baseline in Lumbar Spine Bone Mineral Density 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. Least squares means based on repeated measures model adjusting for treatment, visit, baseline value, and strata (4 strata from the combination of baseline use of steroid and previous use of biologic).
    Percent Change From Baseline in Femoral Neck Bone Mineral Density at Month 1
    Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from baseline to Month 1 calculated using ((Month 1 value - baseline value) / baseline value ) x 100. Least squares means based on repeated measures model adjusting for treatment, visit, baseline value, and strata (4 strata from the combination of baseline use of steroid and previous use of biologic).
    Percent Change From Baseline in Femoral Neck Bone Mineral Density at Month 6
    Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from baseline to Month 6 calculated using ((Month 6 value - baseline value) / baseline value ) x 100. Least squares means based on repeated measures model adjusting for treatment, visit, baseline value, and strata (4 strata from the combination of baseline use of steroid and previous use of biologic).
    Percent Change From Baseline in Femoral Neck Bone Mineral Density 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. Least squares means based on repeated measures model adjusting for treatment, visit, baseline value, and strata (4 strata from the combination of baseline use of steroid and previous use of biologic).
    Percent Change From Baseline in Total Hip Bone Mineral Density at Month 1
    Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from baseline to Month 1 calculated using ((Month 1 value - baseline value) / baseline value ) x 100. Least squares means based on repeated measures model adjusting for treatment, visit, baseline value, and strata (4 strata from the combination of baseline use of steroid and previous use of biologic).
    Percent Change From Baseline in Total Hip Bone Mineral Density at Month 6
    Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from baseline to Month 6 calculated using ((Month 6 value - baseline value) / baseline value ) x 100. Least squares means based on repeated measures model adjusting for treatment, visit, baseline value, and strata (4 strata from the combination of baseline use of steroid and previous use of biologic).
    Percent Change From Baseline in Total Hip Bone Mineral Density 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. Least squares means based on repeated measures model adjusting for treatment, visit, baseline value, and strata (4 strata from the combination of baseline use of steroid and previous use of biologic).
    Percent Change From Baseline in Serum Collagen C-Telopeptide (CTX) at Month 3
    Percent change from baseline to Month 3 in serum Collagen C-Telopeptide (CTX) Type I calculated using ((Month 3 value - Baseline value) / Baseline value ) x 100.
    Percent Change From Baseline in Serum CTX at Month 6
    Percent change from baseline to Month 6 in serum Collagen C-Telopeptide (CTX) Type I calculated using ((Month 6 value - Baseline value) / Baseline value ) x 100.
    Percent Change From Baseline in Serum CTX at Month 12
    Percent change from Baseline to Month 12 in serum C-Telopeptide (CTX) Type I calculated using ((Month 12 value - Baseline value) / Baseline value ) x 100.
    Percent Change From Baseline in Procollagen 1 N-terminal Peptide (P1NP) at Month 3
    Percent change from baseline to Month 3 in procollagen 1 N-terminal peptide (P1NP) calculated using ((Month 3 value - Baseline value) / Baseline value ) x 100.
    Percent Change From Baseline in P1NP at Month 6
    Percent change from baseline to Month 6 in procollagen 1 N-terminal peptide (P1NP) calculated using ((Month 6 value - Baseline value) / Baseline value ) x 100.
    Percent Change From Baseline in P1NP at Month 12
    Percent change from baseline to Month 12 in procollagen 1 N-terminal peptide (P1NP) calculated using ((Month 12 value - Baseline value) / Baseline value ) x 100.
    Percent Change From Baseline in Urine Type II Collagen C-telopeptide (C-Tx) /Creatinine at Month 3
    Percent change from baseline to Month 3 in urine Type II collagen C-Telopeptide (CTX)/Creatinine calculated using ((Month 3 value - Baseline value) / Baseline value ) x 100.
    Percent Change From Baseline in Urine Type II C-Tx /Creatinine at Month 6
    Percent change from baseline to Month 6 in urine Type II collagen C-Telopeptide (CTX)/Creatinine calculated using ((Month 6 value - Baseline value) / Baseline value ) x 100.
    Percent Change From Baseline in Urine Type II C-Tx /Creatinine at Month 12
    Percent change from baseline to Month 12 in urine Type II collagen C-Telopeptide (CTX)/Creatinine calculated using ((Month 12 value - Baseline value) / Baseline value ) x 100.
    Number of Participants With Anti-Denosumab Binding Antibodies
    Serum from participants was tested for antibodies to denosumab by immuoassay at months 1, 3, 6 and 12. The number of participants with anti-denosumab antibodies at any assessment is reported.
    Number of Participants With Anti-Denosumab Binding Antibody and Neutralizing Antibody
    Serum from participants testing positive for anti-denosumab binding antibodies was tested in a cell-based bioassay for neutralizing activity against denosumab.
    Change From Baseline in Albumin at Month 1
    Laboratory Chemistry Albumin
    Change From Baseline in Albumin at Month 3
    Laboratory chemistry albumin
    Change From Baseline in Albumin at Month 6
    Laboratory chemistry albumin
    Change From Baseline in Albumin at Month 12
    Laboratory chemistry albumin
    Change From Baseline in Alkaline Phosphatase at Month 1
    Laboratory chemistry alkaline phoshatatse
    Change From Baseline in Alkaline Phosphatase at Month 3
    Laboratory chemisrty alkaline phosphatase
    Change From Baseline in Alkaline Phosphatase at Month 6
    Laboratory chemistry alkaline phosphatase
    Change From Baseline in Alkaline Phosphatase at Month 12
    Laboratory chemistry alkaline phosphatase
    Change From Baseline in Bicarbonate at Month 1
    Laboratory chemistry bicarbonate
    Change From Baseline in Bicarbonate at Month 3
    Laboratory chemistry bicarbonate
    Change From Baseline in Bicarbonate at Month 6
    Laboratory chemistry bicarbonate
    Change From Baseline in Bicarbonate at Month 12
    Laboratory chemistry bicarbonate
    Change From Baseline in Total Bilirubin at Month 1
    Laboratory chemistry total bilirubin
    Change From Baseline in Total Bilirubin at Month 3
    Laboratory chemistry total bilirubin
    Change From Baseline in Total Bilirubin at Month 6
    Laboratory chemistry total bilirubin
    Change From Baseline in Total Bilirubin at Month 12
    Laboratory chemistry total bilirubin
    Change From Baseline in Blood Urea Nitrogen at Month 1
    Laboratory chemistry blood urea nitrogen
    Change From Baseline in Blood Urea Nitrogen at Month 3
    Laboratory chemistry blood urea nitrogen
    Change From Baseline in Blood Urea Nitrogen at Month 6
    Laboratory chemistry blood urea nitrogen
    Change From Baseline in Blood Urea Nitrogen at Month 12
    Laboratory chemistry blood urea nitrogen
    Change From Baseline in Calcium at Month 1
    Laboratory chemistry calcium
    Change From Baseline in Calcium at Month 3
    Laboratory chemistry calcium
    Change From Baseline in Calcium at Month 6
    Laboratory chemistry calcium
    Change From Baseline in Calcium at Month 12
    Laboratory chemistry calcium
    Change From Baseline in Calcium (Corrected) at Month 1
    Laboratory chemistry albumin-adjusted calcium
    Change From Baseline in Calcium (Corrected) at Month 3
    Laboratory chemistry albumin-adjusted calcium
    Change From Baseline in Calcium (Corrected) at Month 6
    Laboratory chemistry albumin-adjusted calcium
    Change From Baseline in Calcium (Corrected) at Month 12
    Laboratory chemistry albumin-adjusted calcium
    Change From Baseline in Chloride at Month 1
    Laboratory chemistry chloride
    Change From Baseline in Chloride at Month 3
    Laboratory chemistry chloride
    Change From Baseline in Chloride at Month 6
    Laboratory chemistry chloride
    Change From Baseline in Chloride at Month 12
    Laboratory chemistry chloride
    Change From Baseline in Creatinine at Month 1
    Laboratory chemistry creatinine
    Change From Baseline in Creatinine at Month 3
    Laboratory chemistry creatinine
    Change From Baseline in Creatinine at Month 6
    Laboratory chemistry creatinine
    Change From Baseline in Creatinine at Month 12
    Laboratory chemistry creatinine
    Change From Baseline in Gamma-Glutamyl Transferase at Month 1
    Laboratory chemistry gamma-glutamyl transferase
    Change From Baseline in Gamma-Glutamyl Transferase at Month 3
    Laboratory chemistry gamma-glutamyl transferase
    Change From Baseline in Gamma-Glutamyl Transferase at Month 6
    Laboratory chemistry gamma-glutamyl transferase
    Change From Baseline in Gamma-Glutamyl Transferase at Month 12
    Laboratory chemistry gamma-glutamyl transferase
    Change From Baseline in Glucose at Month 1
    Laboratory chemistry glucose
    Change From Baseline in Glucose at Month 3
    Laboratory chemistry glucose
    Change From Baseline in Glucose at Month 6
    Laboratory chemistry glucose
    Change From Baseline in Glucose at Month 12
    Laboratory chemistry glucose
    Change From Baseline in Potassium at Month 1
    Laboratory chemistry potassium
    Change From Baseline in Potassium at Month 3
    Laboratory chemistry potassium
    Change From Baseline in Potassium at Month 6
    Laboratory chemistry potassium
    Change From Baseline in Potassium at Month 12
    Laboratory chemistry potassium
    Change From Baseline in Magnesium at Month 1
    Laboratory chemistry magnesium
    Change From Baseline in Magnesium at Month 3
    Laboratory chemistry magnesium
    Change From Baseline in Magnesium at Month 6
    Laboratory chemistry magnesium
    Change From Baseline in Magnesium at Month 12
    Laboratory chemistry magnesium
    Change From Baseline in Sodium at Month 1
    Laboratory chemistry sodium
    Change From Baseline in Sodium at Month 3
    Change From Baseline in Sodium at Month 3
    Change From Baseline in Sodium at Month 6
    Laboratory chemistry sodium
    Change From Baseline in Sodium at Month 12
    Laboratory chemistry sodium
    Change From Baseline in Phosphorus at Month 1
    Laboratory chemistry phosphorus
    Change From Baseline in Phosphorus at Month 3
    Laboratory chemistry phosphorus
    Change From Baseline in Phosphorus at Month 6
    Laboratory chemistry phosphorus
    Change From Baseline in Phosphorus at Month 12
    Change From Baseline in Phosphorus at Month 12
    Change From Baseline in Total Protein at Month 1
    Laboratory chemistry total protein
    Change From Baseline in Total Protein at Month 3
    Laboratory chemistry total protein
    Change From Baseline in Total Protein at Month 6
    Laboratory chemistry total protein
    Change From Baseline in Total Protein at Month 12
    Laboratory chemistry total protein
    Change From Baseline in Aspartate Amino Transferase at Month 1
    Laboratory chemistry aspartate amino transferase
    Change From Baseline in Aspartate Amino Transferase at Month 3
    Laboratory chemistry aspartate amino transferase
    Change From Baseline in Aspartate Amino Transferase
    Laboratory chemistry aspartate amino transferase
    Change From Baseline in Aspartate Amino Transferase at Month 12
    Laboratory chemistry aspartate amino transferase
    Change From Baseline in Alanine Amino Transferase at Month 1
    Laboratory chemistry alanine amino transferase
    Change From Baseline in Alanine Amino Transferase at Month 3
    Laboratory Chemistry alanine amino transferase
    Change From Baseline in Alanine Amino Transferase at Month 6
    Laboratory chemistry alanine amino transferase
    Change From Baseline in Alanine Amino Transferase at Month 12
    Laboratory chemistry alanine amino transferase
    Change From Baseline in Basophils at Month 1
    Laboratory hematology basophils
    Change From Baseline in Basophils at Month 3
    Laboratory hematology basophils
    Change From Baseline in Basophils at Month 6
    Laboratory hematology basophils
    Change From Baseline in Basophils at Month 12
    Laboratory hematology basophils
    Change From Baseline in Eosinophils at Month 1
    Laboratory hematology eosinophils
    Change From Baseline in Eosinophils at Month 3
    Laboratory hematology eosinophils
    Change From Baseline in Eosinophils at Month 6
    Laboratory hematology eosinophils
    Change From Baseline in Eosinophils at Month 12
    Laboratory hematology eosinophils
    Change From Baseline in Hematocrit at Month 1
    Laboratory hematology hematocrit
    Change From Baseline in Hematocrit at Month 3
    Laboratory hematology hematocrit
    Change From Baseline in Hematocrit at Month 6
    Laboratory hematology hematocrit
    Change From Baseline in Hematocrit at Month 12
    Laboratory hematology hematocrit
    Change From Baseline in Hemoglobin at Month 1
    Laboratory hematology hemoglobin
    Change From Baseline in Hemoglobin at Month 3
    Laboratory hematology hemoglobin
    Change From Baseline in Hemoglobin at Month 6
    Laboratory hematology hemoglobin
    Change From Baseline in Hemoglobin at Month 12
    Laboratory hematology hemoglobin
    Change From Baseline in Lymphocytes at Month 1
    Laboratory hematology lymphocytes
    Change From Baseline in Lymphocytes at Month 3
    Laboratory hematology lymphocytes
    Change From Baseline in Lymphocytes at Month 6
    Laboratory hematology lymphocytes
    Change From Baseline in Lymphocytes at Month 12
    Laboratory hematology lymphocytes
    Change From Baseline in Monocytes at Month 1
    Laboratory hematology monocytes
    Change From Baseline in Monocytes at Month 3
    Laboratory hematology monocytes
    Change From Baseline in Monocytes at Month 6
    Laboratory hematology monocytes
    Change From Baseline in Monocytes at Month 12
    Laboratory hematology monocytes
    Change From Baseline in Total Neutrophils at Month 1
    Laboratory hematology total neutrophils
    Change From Baseline in Total Neutrophils at Month 3
    Laboratory hematology total neutrophils
    Change From Baseline in Total Neutrophils at Month 6
    Laboratory hematology total neutrophils
    Change From Baseline in Total Neutrophils at Month 12
    Laboratory hematology total neutrophils
    Change From Baseline in Platelets at Month 1
    Laboratory hematology platelets
    Change From Baseline in Platelets at Month 3
    Laboratory hematology platelets
    Change From Baseline in Platelets at Month 6
    Laboratory hematology platelets
    Change From Baseline in Platelets at Month 12
    Laboratory hematology platelets
    Change From Baseline in Red Blood Cells at Month 1
    Laboratory hematology red blood cells
    Change From Baseline in Red Blood Cells at Month 3
    Laboratory hematology red blood cells
    Change From Baseline in Red Blood Cells at Month 6
    Laboratory hematology red blood cells
    Change From Baseline in Red Blood Cells at Month 12
    Laboratory hematology red blood cells
    Change From Baseline in White Blood Cells at Month 1
    Laboratory hematology white blood cells
    Change From Baseline in White Blood Cells at Month 3
    Laboratpry hematology white blood cells
    Change From Baseline in White Blood Cells at Month 6
    Laboratory hematology white blood cells
    Change From Baseline in White Blood Cells at Month 12
    Laboratory hematology white blood cells
    Number of Participants With Laboratory Common Terminology Criteria for Adverse Events (CTCAE) Grade Greater or Equal to 3
    Participants with laboratory toxicity of grade 3 or 4, graded according to the Common Terminology Criteria for Adverse Events, version 3.0, on the following general guideline: Grade 1 - Mild AE; Grade 2 - Moderate AE; Grade 3 - Severe AE; Grade 4 - Life-threatening or disabling AE; Grade 5 - Death related to AE.

    Full Information

    First Posted
    November 5, 2004
    Last Updated
    October 4, 2021
    Sponsor
    Amgen
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    1. Study Identification

    Unique Protocol Identification Number
    NCT00095498
    Brief Title
    Efficacy, Safety and Tolerability of Denosumab in the Treatment of Rheumatoid Arthritis
    Official Title
    A Randomized, Double-blind, Placebo-controlled, Multi-dose Phase 2 Study to Determine the Efficacy, Safety and Tolerability of Denosumab in the Treatment of Rheumatoid Arthritis
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    October 2021
    Overall Recruitment Status
    Completed
    Study Start Date
    August 11, 2004 (Actual)
    Primary Completion Date
    April 1, 2007 (Actual)
    Study Completion Date
    April 1, 2007 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Amgen

    4. Oversight

    5. Study Description

    Brief Summary
    This study will determine the efficacy, safety, and tolerability of denosumab (AMG 162) in the treatment of Rheumatoid Arthritis (RA).

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Rheumatoid Arthritis
    Keywords
    arthritis, joint pain, Methotrexate

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 2
    Interventional Study Model
    Parallel Assignment
    Masking
    ParticipantInvestigator
    Allocation
    Randomized
    Enrollment
    227 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Denosumab 180 mg
    Arm Type
    Experimental
    Arm Description
    Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.
    Arm Title
    Denosumab 60 mg
    Arm Type
    Experimental
    Arm Description
    Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.
    Arm Title
    Placebo
    Arm Type
    Placebo Comparator
    Arm Description
    Participants received placebo subcutaneous injections on Day 1 and at Month 6.
    Intervention Type
    Drug
    Intervention Name(s)
    placebo
    Intervention Description
    placebo subcutaneous injection
    Intervention Type
    Drug
    Intervention Name(s)
    denosumab
    Other Intervention Name(s)
    AMG 162
    Intervention Description
    For subcutaneous injection
    Primary Outcome Measure Information:
    Title
    Change From Baseline in Rheumatoid Arthritis Erosion Score Measured From MRI Assessments (RA-MRI ES) at Month 6
    Description
    Fifteen sites in each wrist and 10 sites in each hand were assessed by a blinded and independent reader. Each site was scored from 0 to 10 (in accordance with the European League Against Rheumatism [EULAR]-Outcome Measures in Rheumatology Clinical Trials convention), with each unit increment representing 10% incremental loss of the peripheral 1 cm of articular bone. The Erosion Score is a sum of erosion scores from 50 joint sites in both hands/wrists and ranges from 0 (normal, no erosion) to 500 (worst possible erosion).
    Time Frame
    Baseline, Month 6
    Secondary Outcome Measure Information:
    Title
    Change From Baseline in Radiographic Total Modified Sharp Score (TSS) at Month 12
    Description
    TSS is the sum of erosion and joint space narrowing scores obtained from radiographs of the hands and feet, assessed by 2 independent readers. The joint erosion score is a summary of erosion severity in 32 joints of the hands and 12 joints in the feet. Each joint was scored, according to the surface area involved, from 0 (no erosion) to 5 (extensive loss of bone from more than one half of the articulating bone). Because each side of a foot joint was graded on this scale, the maximum erosion score for a foot joint was 10 and the maximal erosion score was 280. Joint Space Narrowing (JSN) Score summarizes the severity of JSN in 30 joints of the hands and 12 joints of the feet. Assessment of JSN for each hand (15 joints per hand) and foot (6 joints per foot), including subluxation, was scored from 0 (normal JSN) to 4 (complete loss of joint space, bony ankylosis, or luxation), with a maximum JSN score of 168. The TSS ranged from 0 (normal) to 448 (worst).
    Time Frame
    Baseline, Month 12
    Title
    Change From Baseline in Radiographic Total Modified Sharp Score (TSS) at Month 6
    Description
    TSS is the sum of erosion and joint space narrowing scores obtained from radiographs of the hands and feet, assessed by 2 independent readers. The joint erosion score is a summary of erosion severity in 32 joints of the hands and 12 joints in the feet. Each joint was scored, according to the surface area involved, from 0 (no erosion) to 5 (extensive loss of bone from more than one half of the articulating bone). Because each side of a foot joint was graded on this scale, the maximum erosion score for a foot joint was 10 and the maximal erosion score was 280. Joint Space Narrowing (JSN) Score summarizes the severity of JSN in 30 joints of the hands and 12 joints of the feet. Assessment of JSN for each hand (15 joints per hand) and foot (6 joints per foot), including subluxation, was scored from 0 (normal JSN) to 4 (complete loss of joint space, bony ankylosis, or luxation), with a maximum JSN score of 168. The TSS ranged from 0 (normal) to 448 (worst).
    Time Frame
    Baseline, Month 6
    Title
    Change From Baseline in Radiographic Erosion Score at Month 12
    Description
    The joint erosion score is a summary of erosion severity in 32 joints of the hands and 12 joints in the feet, obtained from radiographs of the hands and feet and assessed by 2 independent readers. Each joint was scored, according to the surface area involved, from 0 (no erosion) to 5 (extensive loss of bone from more than one half of the articulating bone). Because each side of a foot joint was graded on this scale, the maximum erosion score for a foot joint was 10 and the maximal erosion score was 280.
    Time Frame
    Baseline, Month 12
    Title
    Change From Baseline in Radiographic Erosion Score at Month 6
    Description
    The joint erosion score is a summary of erosion severity in 32 joints of the hands and 12 joints in the feet, obtained from radiographs of the hands and feet and assessed by 2 independent readers. Each joint was scored, according to the surface area involved, from 0 (no erosion) to 5 (extensive loss of bone from more than one half of the articulating bone). Because each side of a foot joint was graded on this scale, the maximum erosion score for a foot joint was 10 and the maximal erosion score was 280.
    Time Frame
    Baseline, Month 6
    Title
    Change From Baseline in Radiographic Joint Space Narrowing Score at Month 12
    Description
    Joint Space Narrowing (JSN) Score summarizes the severity of JSN in 30 joints of the hands and 12 joints of the feet obtained from radiographs of the hands and feet and assessed by 2 independent readers. Assessment of JSN for each hand (15 joints per hand) and foot (6 joints per foot), including subluxation, was scored from 0 (normal JSN) to 4 (complete loss of joint space, bony ankylosis, or luxation), with a maximum JSN score (indicating worst joint space narrowing) of 168.
    Time Frame
    Baseline, Month 12
    Title
    Change From Baseline in Radiographic Joint Space Narrowing Score at Month 6
    Description
    Joint Space Narrowing (JSN) Score summarizes the severity of JSN in 30 joints of the hands and 12 joints of the feet obtained from radiographs of the hands and feet and assessed by 2 independent readers. Assessment of JSN for each hand (15 joints per hand) and foot (6 joints per foot), including subluxation, was scored from 0 (normal JSN) to 4 (complete loss of joint space, bony ankylosis, or luxation), with a maximum JSN score (indicating worst joint space narrowing) of 168.
    Time Frame
    Baseline, Month 6
    Title
    Percent Change From Baseline in Lumbar Spine Bone Mineral Density at Month 1
    Description
    Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from baseline to Month 1 calculated using ((month 1 value - baseline value) / baseline value ) x 100. Least squares means are based on a repeated measures model adjusting for treatment, visit, baseline value, and strata (4 strata from the combination of baseline use of steroid and previous use of biologic).
    Time Frame
    Baseline, Month 1
    Title
    Percent Change From Baseline in Lumbar Spine Bone Mineral Density at Month 6
    Description
    Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from baseline to month 6 calculated using ((month 6 value - baseline value) / baseline value ) x 100. Least squares means are based on a repeated measures model adjusting for treatment, visit, baseline value, and strata (4 strata from the combination of baseline use of steroid and previous use of biologic).
    Time Frame
    Baseline, month 6
    Title
    Percent Change From Baseline in Lumbar Spine Bone Mineral Density at Month 12
    Description
    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. Least squares means based on repeated measures model adjusting for treatment, visit, baseline value, and strata (4 strata from the combination of baseline use of steroid and previous use of biologic).
    Time Frame
    Baseline, Month 12
    Title
    Percent Change From Baseline in Femoral Neck Bone Mineral Density at Month 1
    Description
    Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from baseline to Month 1 calculated using ((Month 1 value - baseline value) / baseline value ) x 100. Least squares means based on repeated measures model adjusting for treatment, visit, baseline value, and strata (4 strata from the combination of baseline use of steroid and previous use of biologic).
    Time Frame
    Baseline, Month 1
    Title
    Percent Change From Baseline in Femoral Neck Bone Mineral Density at Month 6
    Description
    Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from baseline to Month 6 calculated using ((Month 6 value - baseline value) / baseline value ) x 100. Least squares means based on repeated measures model adjusting for treatment, visit, baseline value, and strata (4 strata from the combination of baseline use of steroid and previous use of biologic).
    Time Frame
    Baseline, Month 6
    Title
    Percent Change From Baseline in Femoral Neck Bone Mineral Density at Month 12
    Description
    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. Least squares means based on repeated measures model adjusting for treatment, visit, baseline value, and strata (4 strata from the combination of baseline use of steroid and previous use of biologic).
    Time Frame
    Baseline, Month 12
    Title
    Percent Change From Baseline in Total Hip Bone Mineral Density at Month 1
    Description
    Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from baseline to Month 1 calculated using ((Month 1 value - baseline value) / baseline value ) x 100. Least squares means based on repeated measures model adjusting for treatment, visit, baseline value, and strata (4 strata from the combination of baseline use of steroid and previous use of biologic).
    Time Frame
    Baseline, Month 1
    Title
    Percent Change From Baseline in Total Hip Bone Mineral Density at Month 6
    Description
    Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from baseline to Month 6 calculated using ((Month 6 value - baseline value) / baseline value ) x 100. Least squares means based on repeated measures model adjusting for treatment, visit, baseline value, and strata (4 strata from the combination of baseline use of steroid and previous use of biologic).
    Time Frame
    Baseline, Month 6
    Title
    Percent Change From Baseline in Total Hip Bone Mineral Density at Month 12
    Description
    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. Least squares means based on repeated measures model adjusting for treatment, visit, baseline value, and strata (4 strata from the combination of baseline use of steroid and previous use of biologic).
    Time Frame
    Baseline, Month 12
    Title
    Percent Change From Baseline in Serum Collagen C-Telopeptide (CTX) at Month 3
    Description
    Percent change from baseline to Month 3 in serum Collagen C-Telopeptide (CTX) Type I calculated using ((Month 3 value - Baseline value) / Baseline value ) x 100.
    Time Frame
    Baseline, Month 3
    Title
    Percent Change From Baseline in Serum CTX at Month 6
    Description
    Percent change from baseline to Month 6 in serum Collagen C-Telopeptide (CTX) Type I calculated using ((Month 6 value - Baseline value) / Baseline value ) x 100.
    Time Frame
    Baseline, Month 6
    Title
    Percent Change From Baseline in Serum CTX at Month 12
    Description
    Percent change from Baseline to Month 12 in serum C-Telopeptide (CTX) Type I calculated using ((Month 12 value - Baseline value) / Baseline value ) x 100.
    Time Frame
    Baseline, Month 12
    Title
    Percent Change From Baseline in Procollagen 1 N-terminal Peptide (P1NP) at Month 3
    Description
    Percent change from baseline to Month 3 in procollagen 1 N-terminal peptide (P1NP) calculated using ((Month 3 value - Baseline value) / Baseline value ) x 100.
    Time Frame
    Baseline, Month 3
    Title
    Percent Change From Baseline in P1NP at Month 6
    Description
    Percent change from baseline to Month 6 in procollagen 1 N-terminal peptide (P1NP) calculated using ((Month 6 value - Baseline value) / Baseline value ) x 100.
    Time Frame
    Baseline, Month 6
    Title
    Percent Change From Baseline in P1NP at Month 12
    Description
    Percent change from baseline to Month 12 in procollagen 1 N-terminal peptide (P1NP) calculated using ((Month 12 value - Baseline value) / Baseline value ) x 100.
    Time Frame
    Baseline, Month 12
    Title
    Percent Change From Baseline in Urine Type II Collagen C-telopeptide (C-Tx) /Creatinine at Month 3
    Description
    Percent change from baseline to Month 3 in urine Type II collagen C-Telopeptide (CTX)/Creatinine calculated using ((Month 3 value - Baseline value) / Baseline value ) x 100.
    Time Frame
    Baseline, Month 3
    Title
    Percent Change From Baseline in Urine Type II C-Tx /Creatinine at Month 6
    Description
    Percent change from baseline to Month 6 in urine Type II collagen C-Telopeptide (CTX)/Creatinine calculated using ((Month 6 value - Baseline value) / Baseline value ) x 100.
    Time Frame
    Baseline, Month 6
    Title
    Percent Change From Baseline in Urine Type II C-Tx /Creatinine at Month 12
    Description
    Percent change from baseline to Month 12 in urine Type II collagen C-Telopeptide (CTX)/Creatinine calculated using ((Month 12 value - Baseline value) / Baseline value ) x 100.
    Time Frame
    Baseline, Month 12
    Title
    Number of Participants With Anti-Denosumab Binding Antibodies
    Description
    Serum from participants was tested for antibodies to denosumab by immuoassay at months 1, 3, 6 and 12. The number of participants with anti-denosumab antibodies at any assessment is reported.
    Time Frame
    Assessed at Baseline and at Months 1, 3, 6 and 12.
    Title
    Number of Participants With Anti-Denosumab Binding Antibody and Neutralizing Antibody
    Description
    Serum from participants testing positive for anti-denosumab binding antibodies was tested in a cell-based bioassay for neutralizing activity against denosumab.
    Time Frame
    Baseline to Month 12
    Title
    Change From Baseline in Albumin at Month 1
    Description
    Laboratory Chemistry Albumin
    Time Frame
    Baseline, month 1
    Title
    Change From Baseline in Albumin at Month 3
    Description
    Laboratory chemistry albumin
    Time Frame
    Baseline, month 3
    Title
    Change From Baseline in Albumin at Month 6
    Description
    Laboratory chemistry albumin
    Time Frame
    Baseline, month 6
    Title
    Change From Baseline in Albumin at Month 12
    Description
    Laboratory chemistry albumin
    Time Frame
    Baseline, month 12
    Title
    Change From Baseline in Alkaline Phosphatase at Month 1
    Description
    Laboratory chemistry alkaline phoshatatse
    Time Frame
    Baseline, month 1
    Title
    Change From Baseline in Alkaline Phosphatase at Month 3
    Description
    Laboratory chemisrty alkaline phosphatase
    Time Frame
    baseline, month 3
    Title
    Change From Baseline in Alkaline Phosphatase at Month 6
    Description
    Laboratory chemistry alkaline phosphatase
    Time Frame
    baseline, month 6
    Title
    Change From Baseline in Alkaline Phosphatase at Month 12
    Description
    Laboratory chemistry alkaline phosphatase
    Time Frame
    baseine, month 12
    Title
    Change From Baseline in Bicarbonate at Month 1
    Description
    Laboratory chemistry bicarbonate
    Time Frame
    baseline, month 1
    Title
    Change From Baseline in Bicarbonate at Month 3
    Description
    Laboratory chemistry bicarbonate
    Time Frame
    baseline, month 3
    Title
    Change From Baseline in Bicarbonate at Month 6
    Description
    Laboratory chemistry bicarbonate
    Time Frame
    Baseline, month 6
    Title
    Change From Baseline in Bicarbonate at Month 12
    Description
    Laboratory chemistry bicarbonate
    Time Frame
    Baseline, Month 12
    Title
    Change From Baseline in Total Bilirubin at Month 1
    Description
    Laboratory chemistry total bilirubin
    Time Frame
    baseline, month 1
    Title
    Change From Baseline in Total Bilirubin at Month 3
    Description
    Laboratory chemistry total bilirubin
    Time Frame
    Baseline, month 3
    Title
    Change From Baseline in Total Bilirubin at Month 6
    Description
    Laboratory chemistry total bilirubin
    Time Frame
    Baseline, month 6
    Title
    Change From Baseline in Total Bilirubin at Month 12
    Description
    Laboratory chemistry total bilirubin
    Time Frame
    Baseline, month 12
    Title
    Change From Baseline in Blood Urea Nitrogen at Month 1
    Description
    Laboratory chemistry blood urea nitrogen
    Time Frame
    Baseline, month 1
    Title
    Change From Baseline in Blood Urea Nitrogen at Month 3
    Description
    Laboratory chemistry blood urea nitrogen
    Time Frame
    Baseline, month 3
    Title
    Change From Baseline in Blood Urea Nitrogen at Month 6
    Description
    Laboratory chemistry blood urea nitrogen
    Time Frame
    Baseline, month 6
    Title
    Change From Baseline in Blood Urea Nitrogen at Month 12
    Description
    Laboratory chemistry blood urea nitrogen
    Time Frame
    baseline, month 12
    Title
    Change From Baseline in Calcium at Month 1
    Description
    Laboratory chemistry calcium
    Time Frame
    baseline. month 1
    Title
    Change From Baseline in Calcium at Month 3
    Description
    Laboratory chemistry calcium
    Time Frame
    Baseline, month 3
    Title
    Change From Baseline in Calcium at Month 6
    Description
    Laboratory chemistry calcium
    Time Frame
    baseline, month 6
    Title
    Change From Baseline in Calcium at Month 12
    Description
    Laboratory chemistry calcium
    Time Frame
    Baseline, month 12
    Title
    Change From Baseline in Calcium (Corrected) at Month 1
    Description
    Laboratory chemistry albumin-adjusted calcium
    Time Frame
    Baseline, month 1
    Title
    Change From Baseline in Calcium (Corrected) at Month 3
    Description
    Laboratory chemistry albumin-adjusted calcium
    Time Frame
    baseline, month 3
    Title
    Change From Baseline in Calcium (Corrected) at Month 6
    Description
    Laboratory chemistry albumin-adjusted calcium
    Time Frame
    Baseline, Month 6
    Title
    Change From Baseline in Calcium (Corrected) at Month 12
    Description
    Laboratory chemistry albumin-adjusted calcium
    Time Frame
    Baselien, Month 12
    Title
    Change From Baseline in Chloride at Month 1
    Description
    Laboratory chemistry chloride
    Time Frame
    baseline, month 1
    Title
    Change From Baseline in Chloride at Month 3
    Description
    Laboratory chemistry chloride
    Time Frame
    Baseline, month 3
    Title
    Change From Baseline in Chloride at Month 6
    Description
    Laboratory chemistry chloride
    Time Frame
    Baseline, month 6
    Title
    Change From Baseline in Chloride at Month 12
    Description
    Laboratory chemistry chloride
    Time Frame
    Baseline, month 12
    Title
    Change From Baseline in Creatinine at Month 1
    Description
    Laboratory chemistry creatinine
    Time Frame
    Baseline, month 1
    Title
    Change From Baseline in Creatinine at Month 3
    Description
    Laboratory chemistry creatinine
    Time Frame
    Baseline, month 3
    Title
    Change From Baseline in Creatinine at Month 6
    Description
    Laboratory chemistry creatinine
    Time Frame
    Baseline, month 6
    Title
    Change From Baseline in Creatinine at Month 12
    Description
    Laboratory chemistry creatinine
    Time Frame
    Baseline, month 12
    Title
    Change From Baseline in Gamma-Glutamyl Transferase at Month 1
    Description
    Laboratory chemistry gamma-glutamyl transferase
    Time Frame
    Baseline, month 1
    Title
    Change From Baseline in Gamma-Glutamyl Transferase at Month 3
    Description
    Laboratory chemistry gamma-glutamyl transferase
    Time Frame
    Baseline, month 3
    Title
    Change From Baseline in Gamma-Glutamyl Transferase at Month 6
    Description
    Laboratory chemistry gamma-glutamyl transferase
    Time Frame
    Baseline, month 6
    Title
    Change From Baseline in Gamma-Glutamyl Transferase at Month 12
    Description
    Laboratory chemistry gamma-glutamyl transferase
    Time Frame
    Baseline, month 12
    Title
    Change From Baseline in Glucose at Month 1
    Description
    Laboratory chemistry glucose
    Time Frame
    Baseline, month 1
    Title
    Change From Baseline in Glucose at Month 3
    Description
    Laboratory chemistry glucose
    Time Frame
    Baseline, month 3
    Title
    Change From Baseline in Glucose at Month 6
    Description
    Laboratory chemistry glucose
    Time Frame
    Baseline, month 6
    Title
    Change From Baseline in Glucose at Month 12
    Description
    Laboratory chemistry glucose
    Time Frame
    baseline, month 12
    Title
    Change From Baseline in Potassium at Month 1
    Description
    Laboratory chemistry potassium
    Time Frame
    Baseline, month 1
    Title
    Change From Baseline in Potassium at Month 3
    Description
    Laboratory chemistry potassium
    Time Frame
    Baseline, month 3
    Title
    Change From Baseline in Potassium at Month 6
    Description
    Laboratory chemistry potassium
    Time Frame
    Baseline, month 6
    Title
    Change From Baseline in Potassium at Month 12
    Description
    Laboratory chemistry potassium
    Time Frame
    Baseline, month 12
    Title
    Change From Baseline in Magnesium at Month 1
    Description
    Laboratory chemistry magnesium
    Time Frame
    Baseline, month 1
    Title
    Change From Baseline in Magnesium at Month 3
    Description
    Laboratory chemistry magnesium
    Time Frame
    Baseline, month 3
    Title
    Change From Baseline in Magnesium at Month 6
    Description
    Laboratory chemistry magnesium
    Time Frame
    Baseline, month 6
    Title
    Change From Baseline in Magnesium at Month 12
    Description
    Laboratory chemistry magnesium
    Time Frame
    Baseline, month 12
    Title
    Change From Baseline in Sodium at Month 1
    Description
    Laboratory chemistry sodium
    Time Frame
    Baseline, month 1
    Title
    Change From Baseline in Sodium at Month 3
    Description
    Change From Baseline in Sodium at Month 3
    Time Frame
    Baseline, Month 3
    Title
    Change From Baseline in Sodium at Month 6
    Description
    Laboratory chemistry sodium
    Time Frame
    Baseline, month 6
    Title
    Change From Baseline in Sodium at Month 12
    Description
    Laboratory chemistry sodium
    Time Frame
    Baseline, month 12
    Title
    Change From Baseline in Phosphorus at Month 1
    Description
    Laboratory chemistry phosphorus
    Time Frame
    Baseline, month 1
    Title
    Change From Baseline in Phosphorus at Month 3
    Description
    Laboratory chemistry phosphorus
    Time Frame
    Baseline, month 3
    Title
    Change From Baseline in Phosphorus at Month 6
    Description
    Laboratory chemistry phosphorus
    Time Frame
    Baseline, month 6
    Title
    Change From Baseline in Phosphorus at Month 12
    Description
    Change From Baseline in Phosphorus at Month 12
    Time Frame
    Baseline, month 12
    Title
    Change From Baseline in Total Protein at Month 1
    Description
    Laboratory chemistry total protein
    Time Frame
    Baseline, month 1
    Title
    Change From Baseline in Total Protein at Month 3
    Description
    Laboratory chemistry total protein
    Time Frame
    Baseline, month 3
    Title
    Change From Baseline in Total Protein at Month 6
    Description
    Laboratory chemistry total protein
    Time Frame
    Baseline, month 6
    Title
    Change From Baseline in Total Protein at Month 12
    Description
    Laboratory chemistry total protein
    Time Frame
    Baseline, month 12
    Title
    Change From Baseline in Aspartate Amino Transferase at Month 1
    Description
    Laboratory chemistry aspartate amino transferase
    Time Frame
    Baseline, month 1
    Title
    Change From Baseline in Aspartate Amino Transferase at Month 3
    Description
    Laboratory chemistry aspartate amino transferase
    Time Frame
    Baseline, month 3
    Title
    Change From Baseline in Aspartate Amino Transferase
    Description
    Laboratory chemistry aspartate amino transferase
    Time Frame
    Baseline, month 6
    Title
    Change From Baseline in Aspartate Amino Transferase at Month 12
    Description
    Laboratory chemistry aspartate amino transferase
    Time Frame
    Baseline, month 12
    Title
    Change From Baseline in Alanine Amino Transferase at Month 1
    Description
    Laboratory chemistry alanine amino transferase
    Time Frame
    Baseline, month 1
    Title
    Change From Baseline in Alanine Amino Transferase at Month 3
    Description
    Laboratory Chemistry alanine amino transferase
    Time Frame
    Baseline, month 3
    Title
    Change From Baseline in Alanine Amino Transferase at Month 6
    Description
    Laboratory chemistry alanine amino transferase
    Time Frame
    Baseline, month 6
    Title
    Change From Baseline in Alanine Amino Transferase at Month 12
    Description
    Laboratory chemistry alanine amino transferase
    Time Frame
    Baseline, month 12
    Title
    Change From Baseline in Basophils at Month 1
    Description
    Laboratory hematology basophils
    Time Frame
    baseline, month 1
    Title
    Change From Baseline in Basophils at Month 3
    Description
    Laboratory hematology basophils
    Time Frame
    Baseline, month 3
    Title
    Change From Baseline in Basophils at Month 6
    Description
    Laboratory hematology basophils
    Time Frame
    Baseline, month 6
    Title
    Change From Baseline in Basophils at Month 12
    Description
    Laboratory hematology basophils
    Time Frame
    Baseline, month 12
    Title
    Change From Baseline in Eosinophils at Month 1
    Description
    Laboratory hematology eosinophils
    Time Frame
    Baseline, month 1
    Title
    Change From Baseline in Eosinophils at Month 3
    Description
    Laboratory hematology eosinophils
    Time Frame
    Baseline, month 3
    Title
    Change From Baseline in Eosinophils at Month 6
    Description
    Laboratory hematology eosinophils
    Time Frame
    Baseline, month 6
    Title
    Change From Baseline in Eosinophils at Month 12
    Description
    Laboratory hematology eosinophils
    Time Frame
    Baseline, month 12
    Title
    Change From Baseline in Hematocrit at Month 1
    Description
    Laboratory hematology hematocrit
    Time Frame
    Baseline, month 1
    Title
    Change From Baseline in Hematocrit at Month 3
    Description
    Laboratory hematology hematocrit
    Time Frame
    Baseline, month 3
    Title
    Change From Baseline in Hematocrit at Month 6
    Description
    Laboratory hematology hematocrit
    Time Frame
    Baseline, month 6
    Title
    Change From Baseline in Hematocrit at Month 12
    Description
    Laboratory hematology hematocrit
    Time Frame
    Baseline, month 12
    Title
    Change From Baseline in Hemoglobin at Month 1
    Description
    Laboratory hematology hemoglobin
    Time Frame
    Baseline, month 1
    Title
    Change From Baseline in Hemoglobin at Month 3
    Description
    Laboratory hematology hemoglobin
    Time Frame
    Baseline, month 3
    Title
    Change From Baseline in Hemoglobin at Month 6
    Description
    Laboratory hematology hemoglobin
    Time Frame
    Baseline, month 6
    Title
    Change From Baseline in Hemoglobin at Month 12
    Description
    Laboratory hematology hemoglobin
    Time Frame
    Baseline, month 12
    Title
    Change From Baseline in Lymphocytes at Month 1
    Description
    Laboratory hematology lymphocytes
    Time Frame
    Baseline, month 1
    Title
    Change From Baseline in Lymphocytes at Month 3
    Description
    Laboratory hematology lymphocytes
    Time Frame
    Baseline, month 3
    Title
    Change From Baseline in Lymphocytes at Month 6
    Description
    Laboratory hematology lymphocytes
    Time Frame
    Baseline, month 6
    Title
    Change From Baseline in Lymphocytes at Month 12
    Description
    Laboratory hematology lymphocytes
    Time Frame
    Baseline, month 12
    Title
    Change From Baseline in Monocytes at Month 1
    Description
    Laboratory hematology monocytes
    Time Frame
    Baseline, month 1
    Title
    Change From Baseline in Monocytes at Month 3
    Description
    Laboratory hematology monocytes
    Time Frame
    Baseline, month 3
    Title
    Change From Baseline in Monocytes at Month 6
    Description
    Laboratory hematology monocytes
    Time Frame
    Baseline, month 6
    Title
    Change From Baseline in Monocytes at Month 12
    Description
    Laboratory hematology monocytes
    Time Frame
    Baseline, month 12
    Title
    Change From Baseline in Total Neutrophils at Month 1
    Description
    Laboratory hematology total neutrophils
    Time Frame
    Baseline, month 1
    Title
    Change From Baseline in Total Neutrophils at Month 3
    Description
    Laboratory hematology total neutrophils
    Time Frame
    Baseline, month 3
    Title
    Change From Baseline in Total Neutrophils at Month 6
    Description
    Laboratory hematology total neutrophils
    Time Frame
    Baseline, month 6
    Title
    Change From Baseline in Total Neutrophils at Month 12
    Description
    Laboratory hematology total neutrophils
    Time Frame
    Baseline, month 12
    Title
    Change From Baseline in Platelets at Month 1
    Description
    Laboratory hematology platelets
    Time Frame
    Baseline, month 1
    Title
    Change From Baseline in Platelets at Month 3
    Description
    Laboratory hematology platelets
    Time Frame
    Baseline, month 3
    Title
    Change From Baseline in Platelets at Month 6
    Description
    Laboratory hematology platelets
    Time Frame
    Baseline, month 6
    Title
    Change From Baseline in Platelets at Month 12
    Description
    Laboratory hematology platelets
    Time Frame
    Baseline, month 12
    Title
    Change From Baseline in Red Blood Cells at Month 1
    Description
    Laboratory hematology red blood cells
    Time Frame
    Baseline, month 1
    Title
    Change From Baseline in Red Blood Cells at Month 3
    Description
    Laboratory hematology red blood cells
    Time Frame
    Baseline, month 3
    Title
    Change From Baseline in Red Blood Cells at Month 6
    Description
    Laboratory hematology red blood cells
    Time Frame
    Baseline, month 6
    Title
    Change From Baseline in Red Blood Cells at Month 12
    Description
    Laboratory hematology red blood cells
    Time Frame
    Baseline, month 12
    Title
    Change From Baseline in White Blood Cells at Month 1
    Description
    Laboratory hematology white blood cells
    Time Frame
    Baseline, month 1
    Title
    Change From Baseline in White Blood Cells at Month 3
    Description
    Laboratpry hematology white blood cells
    Time Frame
    Baseline, month 3
    Title
    Change From Baseline in White Blood Cells at Month 6
    Description
    Laboratory hematology white blood cells
    Time Frame
    Baseline, month 6
    Title
    Change From Baseline in White Blood Cells at Month 12
    Description
    Laboratory hematology white blood cells
    Time Frame
    Baseline, month 12
    Title
    Number of Participants With Laboratory Common Terminology Criteria for Adverse Events (CTCAE) Grade Greater or Equal to 3
    Description
    Participants with laboratory toxicity of grade 3 or 4, graded according to the Common Terminology Criteria for Adverse Events, version 3.0, on the following general guideline: Grade 1 - Mild AE; Grade 2 - Moderate AE; Grade 3 - Severe AE; Grade 4 - Life-threatening or disabling AE; Grade 5 - Death related to AE.
    Time Frame
    Month 1, month 3, month 6, month 12

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Diagnosis of RA. All subjects will be required to have been taking a stable dose of methotrexate. Active RA at screening defined as greater than or equal to 6 swollen joints. The presence of erosive disease Exclusion Criteria: Received any biologic agent (e.g., Enbrel®, Remicade®, Humira®, Kineret®) or Arava® within 8 weeks before randomization; past use of these agents is allowed. Steroid use greater than 15 mg/day. Scheduled for surgery or joint replacement in the hands, wrists or feet.
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    MD
    Organizational Affiliation
    Amgen
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Citations:
    PubMed Identifier
    18438830
    Citation
    Cohen SB, Dore RK, Lane NE, Ory PA, Peterfy CG, Sharp JT, van der Heijde D, Zhou L, Tsuji W, Newmark R; Denosumab Rheumatoid Arthritis Study Group. Denosumab treatment effects on structural damage, bone mineral density, and bone turnover in rheumatoid arthritis: a twelve-month, multicenter, randomized, double-blind, placebo-controlled, phase II clinical trial. Arthritis Rheum. 2008 May;58(5):1299-309. doi: 10.1002/art.23417.
    Results Reference
    background
    PubMed Identifier
    20391513
    Citation
    Deodhar A, Dore RK, Mandel D, Schechtman J, Shergy W, Trapp R, Ory PA, Peterfy CG, Fuerst T, Wang H, Zhou L, Tsuji W, Newmark R. Denosumab-mediated increase in hand bone mineral density associated with decreased progression of bone erosion in rheumatoid arthritis patients. Arthritis Care Res (Hoboken). 2010 Apr;62(4):569-74. doi: 10.1002/acr.20004.
    Results Reference
    background
    PubMed Identifier
    19734132
    Citation
    Dore RK, Cohen SB, Lane NE, Palmer W, Shergy W, Zhou L, Wang H, Tsuji W, Newmark R; Denosumab RA Study Group. Effects of denosumab on bone mineral density and bone turnover in patients with rheumatoid arthritis receiving concurrent glucocorticoids or bisphosphonates. Ann Rheum Dis. 2010 May;69(5):872-5. doi: 10.1136/ard.2009.112920. Epub 2009 Sep 3.
    Results Reference
    background
    PubMed Identifier
    20391509
    Citation
    Sharp JT, Tsuji W, Ory P, Harper-Barek C, Wang H, Newmark R. Denosumab prevents metacarpal shaft cortical bone loss in patients with erosive rheumatoid arthritis. Arthritis Care Res (Hoboken). 2010 Apr;62(4):537-44. doi: 10.1002/acr.20172.
    Results Reference
    background
    Links:
    URL
    http://www.amgentrials.com
    Description
    AmgenTrials clinical trials website
    URL
    http://download.veritasmedicine.com/REGFILES/amgen/Amgen_results_disclaimer.pdf
    Description
    Notice regarding posted summaries of trial results
    URL
    http://download.veritasmedicine.com/REGFILES/amgen/08D_FDAMA_113_Posting_Summary_49_AMG_162_20040144.pdf
    Description
    To access clinical trial results information click on this link

    Learn more about this trial

    Efficacy, Safety and Tolerability of Denosumab in the Treatment of Rheumatoid Arthritis

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