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

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

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

Study Overview

• Status: Completed
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Drug: denosumab; Drug: placebo

• Study Type: Interventional
• Enrollment (Actual): 227
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

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

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Denosumab 180 mg; Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Drug: denosumab; For subcutaneous injection; Other Names: AMG 162
Experimental: Denosumab 60 mg; Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Drug: denosumab; For subcutaneous injection; Other Names: AMG 162
Placebo Comparator: Placebo; Participants received placebo subcutaneous injections on Day 1 and at Month 6.	Drug: placebo; placebo subcutaneous injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	Baseline, Month 6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	Baseline, Month 12
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).	Baseline, Month 6
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.	Baseline, Month 12
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.	Baseline, Month 6
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.	Baseline, Month 12
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.	Baseline, Month 6
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).	Baseline, Month 1
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).	Baseline, month 6
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).	Baseline, Month 12
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).	Baseline, Month 1
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).	Baseline, Month 6
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).	Baseline, Month 12
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).	Baseline, Month 1
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).	Baseline, Month 6
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).	Baseline, Month 12
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.	Baseline, Month 3
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.	Baseline, Month 6
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.	Baseline, Month 12
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.	Baseline, Month 3
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.	Baseline, Month 6
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.	Baseline, Month 12
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.	Baseline, Month 3
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.	Baseline, Month 6
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.	Baseline, Month 12
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.	Assessed at Baseline and at Months 1, 3, 6 and 12.
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.	Baseline to Month 12
Change From Baseline in Albumin at Month 1	Laboratory Chemistry Albumin	Baseline, month 1
Change From Baseline in Albumin at Month 3	Laboratory chemistry albumin	Baseline, month 3
Change From Baseline in Albumin at Month 6	Laboratory chemistry albumin	Baseline, month 6
Change From Baseline in Albumin at Month 12	Laboratory chemistry albumin	Baseline, month 12
Change From Baseline in Alkaline Phosphatase at Month 1	Laboratory chemistry alkaline phoshatatse	Baseline, month 1
Change From Baseline in Alkaline Phosphatase at Month 3	Laboratory chemisrty alkaline phosphatase	baseline, month 3
Change From Baseline in Alkaline Phosphatase at Month 6	Laboratory chemistry alkaline phosphatase	baseline, month 6
Change From Baseline in Alkaline Phosphatase at Month 12	Laboratory chemistry alkaline phosphatase	baseine, month 12
Change From Baseline in Bicarbonate at Month 1	Laboratory chemistry bicarbonate	baseline, month 1
Change From Baseline in Bicarbonate at Month 3	Laboratory chemistry bicarbonate	baseline, month 3
Change From Baseline in Bicarbonate at Month 6	Laboratory chemistry bicarbonate	Baseline, month 6
Change From Baseline in Bicarbonate at Month 12	Laboratory chemistry bicarbonate	Baseline, Month 12
Change From Baseline in Total Bilirubin at Month 1	Laboratory chemistry total bilirubin	baseline, month 1
Change From Baseline in Total Bilirubin at Month 3	Laboratory chemistry total bilirubin	Baseline, month 3
Change From Baseline in Total Bilirubin at Month 6	Laboratory chemistry total bilirubin	Baseline, month 6
Change From Baseline in Total Bilirubin at Month 12	Laboratory chemistry total bilirubin	Baseline, month 12
Change From Baseline in Blood Urea Nitrogen at Month 1	Laboratory chemistry blood urea nitrogen	Baseline, month 1
Change From Baseline in Blood Urea Nitrogen at Month 3	Laboratory chemistry blood urea nitrogen	Baseline, month 3
Change From Baseline in Blood Urea Nitrogen at Month 6	Laboratory chemistry blood urea nitrogen	Baseline, month 6
Change From Baseline in Blood Urea Nitrogen at Month 12	Laboratory chemistry blood urea nitrogen	baseline, month 12
Change From Baseline in Calcium at Month 1	Laboratory chemistry calcium	baseline. month 1
Change From Baseline in Calcium at Month 3	Laboratory chemistry calcium	Baseline, month 3
Change From Baseline in Calcium at Month 6	Laboratory chemistry calcium	baseline, month 6
Change From Baseline in Calcium at Month 12	Laboratory chemistry calcium	Baseline, month 12
Change From Baseline in Calcium (Corrected) at Month 1	Laboratory chemistry albumin-adjusted calcium	Baseline, month 1
Change From Baseline in Calcium (Corrected) at Month 3	Laboratory chemistry albumin-adjusted calcium	baseline, month 3
Change From Baseline in Calcium (Corrected) at Month 6	Laboratory chemistry albumin-adjusted calcium	Baseline, Month 6
Change From Baseline in Calcium (Corrected) at Month 12	Laboratory chemistry albumin-adjusted calcium	Baselien, Month 12
Change From Baseline in Chloride at Month 1	Laboratory chemistry chloride	baseline, month 1
Change From Baseline in Chloride at Month 3	Laboratory chemistry chloride	Baseline, month 3
Change From Baseline in Chloride at Month 6	Laboratory chemistry chloride	Baseline, month 6
Change From Baseline in Chloride at Month 12	Laboratory chemistry chloride	Baseline, month 12
Change From Baseline in Creatinine at Month 1	Laboratory chemistry creatinine	Baseline, month 1
Change From Baseline in Creatinine at Month 3	Laboratory chemistry creatinine	Baseline, month 3
Change From Baseline in Creatinine at Month 6	Laboratory chemistry creatinine	Baseline, month 6
Change From Baseline in Creatinine at Month 12	Laboratory chemistry creatinine	Baseline, month 12
Change From Baseline in Gamma-Glutamyl Transferase at Month 1	Laboratory chemistry gamma-glutamyl transferase	Baseline, month 1
Change From Baseline in Gamma-Glutamyl Transferase at Month 3	Laboratory chemistry gamma-glutamyl transferase	Baseline, month 3
Change From Baseline in Gamma-Glutamyl Transferase at Month 6	Laboratory chemistry gamma-glutamyl transferase	Baseline, month 6
Change From Baseline in Gamma-Glutamyl Transferase at Month 12	Laboratory chemistry gamma-glutamyl transferase	Baseline, month 12
Change From Baseline in Glucose at Month 1	Laboratory chemistry glucose	Baseline, month 1
Change From Baseline in Glucose at Month 3	Laboratory chemistry glucose	Baseline, month 3
Change From Baseline in Glucose at Month 6	Laboratory chemistry glucose	Baseline, month 6
Change From Baseline in Glucose at Month 12	Laboratory chemistry glucose	baseline, month 12
Change From Baseline in Potassium at Month 1	Laboratory chemistry potassium	Baseline, month 1
Change From Baseline in Potassium at Month 3	Laboratory chemistry potassium	Baseline, month 3
Change From Baseline in Potassium at Month 6	Laboratory chemistry potassium	Baseline, month 6
Change From Baseline in Potassium at Month 12	Laboratory chemistry potassium	Baseline, month 12
Change From Baseline in Magnesium at Month 1	Laboratory chemistry magnesium	Baseline, month 1
Change From Baseline in Magnesium at Month 3	Laboratory chemistry magnesium	Baseline, month 3
Change From Baseline in Magnesium at Month 6	Laboratory chemistry magnesium	Baseline, month 6
Change From Baseline in Magnesium at Month 12	Laboratory chemistry magnesium	Baseline, month 12
Change From Baseline in Sodium at Month 1	Laboratory chemistry sodium	Baseline, month 1
Change From Baseline in Sodium at Month 3	Change From Baseline in Sodium at Month 3	Baseline, Month 3
Change From Baseline in Sodium at Month 6	Laboratory chemistry sodium	Baseline, month 6
Change From Baseline in Sodium at Month 12	Laboratory chemistry sodium	Baseline, month 12
Change From Baseline in Phosphorus at Month 1	Laboratory chemistry phosphorus	Baseline, month 1
Change From Baseline in Phosphorus at Month 3	Laboratory chemistry phosphorus	Baseline, month 3
Change From Baseline in Phosphorus at Month 6	Laboratory chemistry phosphorus	Baseline, month 6
Change From Baseline in Phosphorus at Month 12	Change From Baseline in Phosphorus at Month 12	Baseline, month 12
Change From Baseline in Total Protein at Month 1	Laboratory chemistry total protein	Baseline, month 1
Change From Baseline in Total Protein at Month 3	Laboratory chemistry total protein	Baseline, month 3
Change From Baseline in Total Protein at Month 6	Laboratory chemistry total protein	Baseline, month 6
Change From Baseline in Total Protein at Month 12	Laboratory chemistry total protein	Baseline, month 12
Change From Baseline in Aspartate Amino Transferase at Month 1	Laboratory chemistry aspartate amino transferase	Baseline, month 1
Change From Baseline in Aspartate Amino Transferase at Month 3	Laboratory chemistry aspartate amino transferase	Baseline, month 3
Change From Baseline in Aspartate Amino Transferase	Laboratory chemistry aspartate amino transferase	Baseline, month 6
Change From Baseline in Aspartate Amino Transferase at Month 12	Laboratory chemistry aspartate amino transferase	Baseline, month 12
Change From Baseline in Alanine Amino Transferase at Month 1	Laboratory chemistry alanine amino transferase	Baseline, month 1
Change From Baseline in Alanine Amino Transferase at Month 3	Laboratory Chemistry alanine amino transferase	Baseline, month 3
Change From Baseline in Alanine Amino Transferase at Month 6	Laboratory chemistry alanine amino transferase	Baseline, month 6
Change From Baseline in Alanine Amino Transferase at Month 12	Laboratory chemistry alanine amino transferase	Baseline, month 12
Change From Baseline in Basophils at Month 1	Laboratory hematology basophils	baseline, month 1
Change From Baseline in Basophils at Month 3	Laboratory hematology basophils	Baseline, month 3
Change From Baseline in Basophils at Month 6	Laboratory hematology basophils	Baseline, month 6
Change From Baseline in Basophils at Month 12	Laboratory hematology basophils	Baseline, month 12
Change From Baseline in Eosinophils at Month 1	Laboratory hematology eosinophils	Baseline, month 1
Change From Baseline in Eosinophils at Month 3	Laboratory hematology eosinophils	Baseline, month 3
Change From Baseline in Eosinophils at Month 6	Laboratory hematology eosinophils	Baseline, month 6
Change From Baseline in Eosinophils at Month 12	Laboratory hematology eosinophils	Baseline, month 12
Change From Baseline in Hematocrit at Month 1	Laboratory hematology hematocrit	Baseline, month 1
Change From Baseline in Hematocrit at Month 3	Laboratory hematology hematocrit	Baseline, month 3
Change From Baseline in Hematocrit at Month 6	Laboratory hematology hematocrit	Baseline, month 6
Change From Baseline in Hematocrit at Month 12	Laboratory hematology hematocrit	Baseline, month 12
Change From Baseline in Hemoglobin at Month 1	Laboratory hematology hemoglobin	Baseline, month 1
Change From Baseline in Hemoglobin at Month 3	Laboratory hematology hemoglobin	Baseline, month 3
Change From Baseline in Hemoglobin at Month 6	Laboratory hematology hemoglobin	Baseline, month 6
Change From Baseline in Hemoglobin at Month 12	Laboratory hematology hemoglobin	Baseline, month 12
Change From Baseline in Lymphocytes at Month 1	Laboratory hematology lymphocytes	Baseline, month 1
Change From Baseline in Lymphocytes at Month 3	Laboratory hematology lymphocytes	Baseline, month 3
Change From Baseline in Lymphocytes at Month 6	Laboratory hematology lymphocytes	Baseline, month 6
Change From Baseline in Lymphocytes at Month 12	Laboratory hematology lymphocytes	Baseline, month 12
Change From Baseline in Monocytes at Month 1	Laboratory hematology monocytes	Baseline, month 1
Change From Baseline in Monocytes at Month 3	Laboratory hematology monocytes	Baseline, month 3
Change From Baseline in Monocytes at Month 6	Laboratory hematology monocytes	Baseline, month 6
Change From Baseline in Monocytes at Month 12	Laboratory hematology monocytes	Baseline, month 12
Change From Baseline in Total Neutrophils at Month 1	Laboratory hematology total neutrophils	Baseline, month 1
Change From Baseline in Total Neutrophils at Month 3	Laboratory hematology total neutrophils	Baseline, month 3
Change From Baseline in Total Neutrophils at Month 6	Laboratory hematology total neutrophils	Baseline, month 6
Change From Baseline in Total Neutrophils at Month 12	Laboratory hematology total neutrophils	Baseline, month 12
Change From Baseline in Platelets at Month 1	Laboratory hematology platelets	Baseline, month 1
Change From Baseline in Platelets at Month 3	Laboratory hematology platelets	Baseline, month 3
Change From Baseline in Platelets at Month 6	Laboratory hematology platelets	Baseline, month 6
Change From Baseline in Platelets at Month 12	Laboratory hematology platelets	Baseline, month 12
Change From Baseline in Red Blood Cells at Month 1	Laboratory hematology red blood cells	Baseline, month 1
Change From Baseline in Red Blood Cells at Month 3	Laboratory hematology red blood cells	Baseline, month 3
Change From Baseline in Red Blood Cells at Month 6	Laboratory hematology red blood cells	Baseline, month 6
Change From Baseline in Red Blood Cells at Month 12	Laboratory hematology red blood cells	Baseline, month 12
Change From Baseline in White Blood Cells at Month 1	Laboratory hematology white blood cells	Baseline, month 1
Change From Baseline in White Blood Cells at Month 3	Laboratpry hematology white blood cells	Baseline, month 3
Change From Baseline in White Blood Cells at Month 6	Laboratory hematology white blood cells	Baseline, month 6
Change From Baseline in White Blood Cells at Month 12	Laboratory hematology white blood cells	Baseline, month 12
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.	Month 1, month 3, month 6, month 12

Collaborators and Investigators

• Sponsor: Amgen

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.

Helpful Links

• AmgenTrials clinical trials website
• Notice regarding posted summaries of trial results
• To access clinical trial results information click on this link

Study record dates

Study Major Dates

• Study Start (Actual): August 11, 2004
• Primary Completion (Actual): April 1, 2007
• Study Completion (Actual): April 1, 2007

Study Registration Dates

• First Submitted: November 5, 2004
• First Submitted That Met QC Criteria: November 5, 2004
• First Posted (Estimate): November 8, 2004

Study Record Updates

• Last Update Posted (Actual): October 25, 2021
• Last Update Submitted That Met QC Criteria: October 4, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: joint pain; Methotrexate; arthritis
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid; Physiological Effects of Drugs; Bone Density Conservation Agents; Denosumab
• Other Study ID Numbers: 20040144