Clinical trial NCT00095498: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Rheumatoid Arthritis
Keywords: arthritis
joint pain
Methotrexate
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2004-11-08
Enrollment: 227
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


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.

Primary outcomes:
measure: Change From Baseline in Rheumatoid Arthritis Erosion Score Measured From MRI Assessments (RA-MRI ES) at Month 6
timeFrame: Baseline, Month 6
Secondary outcomes:
measure: Change From Baseline in Radiographic Total Modified Sharp Score (TSS) at Month 12
timeFrame: Baseline, Month 12
measure: Change From Baseline in Radiographic Total Modified Sharp Score (TSS) at Month 6
timeFrame: Baseline, Month 6
measure: Change From Baseline in Radiographic Erosion Score at Month 12
timeFrame: Baseline, Month 12
measure: Change From Baseline in Radiographic Erosion Score at Month 6
timeFrame: Baseline, Month 6
measure: Change From Baseline in Radiographic Joint Space Narrowing Score at Month 12
timeFrame: Baseline, Month 12
measure: Change From Baseline in Radiographic Joint Space Narrowing Score at Month 6
timeFrame: Baseline, Month 6
measure: Percent Change From Baseline in Lumbar Spine Bone Mineral Density at Month 1
timeFrame: Baseline, Month 1
measure: Percent Change From Baseline in Lumbar Spine Bone Mineral Density at Month 6
timeFrame: Baseline, month 6
measure: Percent Change From Baseline in Lumbar Spine Bone Mineral Density at Month 12
timeFrame: Baseline, Month 12
measure: Percent Change From Baseline in Femoral Neck Bone Mineral Density at Month 1
timeFrame: Baseline, Month 1
measure: Percent Change From Baseline in Femoral Neck Bone Mineral Density at Month 6
timeFrame: Baseline, Month 6
measure: Percent Change From Baseline in Femoral Neck Bone Mineral Density at Month 12
timeFrame: Baseline, Month 12
measure: Percent Change From Baseline in Total Hip Bone Mineral Density at Month 1
timeFrame: Baseline, Month 1
measure: Percent Change From Baseline in Total Hip Bone Mineral Density at Month 6
timeFrame: Baseline, Month 6
measure: Percent Change From Baseline in Total Hip Bone Mineral Density at Month 12
timeFrame: Baseline, Month 12
measure: Percent Change From Baseline in Serum Collagen C-Telopeptide (CTX) at Month 3
timeFrame: Baseline, Month 3
measure: Percent Change From Baseline in Serum CTX at Month 6
timeFrame: Baseline, Month 6
measure: Percent Change From Baseline in Serum CTX at Month 12
timeFrame: Baseline, Month 12
measure: Percent Change From Baseline in Procollagen 1 N-terminal Peptide (P1NP) at Month 3
timeFrame: Baseline, Month 3
measure: Percent Change From Baseline in P1NP at Month 6
timeFrame: Baseline, Month 6
measure: Percent Change From Baseline in P1NP at Month 12
timeFrame: Baseline, Month 12
measure: Percent Change From Baseline in Urine Type II Collagen C-telopeptide (C-Tx) /Creatinine at Month 3
timeFrame: Baseline, Month 3
measure: Percent Change From Baseline in Urine Type II C-Tx /Creatinine at Month 6
timeFrame: Baseline, Month 6
measure: Percent Change From Baseline in Urine Type II C-Tx /Creatinine at Month 12
timeFrame: Baseline, Month 12
measure: Number of Participants With Anti-Denosumab Binding Antibodies
timeFrame: Assessed at Baseline and at Months 1, 3, 6 and 12.
measure: Number of Participants With Anti-Denosumab Binding Antibody and Neutralizing Antibody
timeFrame: Baseline to Month 12
measure: Change From Baseline in Albumin at Month 1
timeFrame: Baseline, month 1
measure: Change From Baseline in Albumin at Month 3
timeFrame: Baseline, month 3
measure: Change From Baseline in Albumin at Month 6
timeFrame: Baseline, month 6
measure: Change From Baseline in Albumin at Month 12
timeFrame: Baseline, month 12
measure: Change From Baseline in Alkaline Phosphatase at Month 1
timeFrame: Baseline, month 1
measure: Change From Baseline in Alkaline Phosphatase at Month 3
timeFrame: baseline, month 3
measure: Change From Baseline in Alkaline Phosphatase at Month 6
timeFrame: baseline, month 6
measure: Change From Baseline in Alkaline Phosphatase at Month 12
timeFrame: baseine, month 12
measure: Change From Baseline in Bicarbonate at Month 1
timeFrame: baseline, month 1
measure: Change From Baseline in Bicarbonate at Month 3
timeFrame: baseline, month 3
measure: Change From Baseline in Bicarbonate at Month 6
timeFrame: Baseline, month 6
measure: Change From Baseline in Bicarbonate at Month 12
timeFrame: Baseline, Month 12
measure: Change From Baseline in Total Bilirubin at Month 1
timeFrame: baseline, month 1
measure: Change From Baseline in Total Bilirubin at Month 3
timeFrame: Baseline, month 3
measure: Change From Baseline in Total Bilirubin at Month 6
timeFrame: Baseline, month 6
measure: Change From Baseline in Total Bilirubin at Month 12
timeFrame: Baseline, month 12
measure: Change From Baseline in Blood Urea Nitrogen at Month 1
timeFrame: Baseline, month 1
measure: Change From Baseline in Blood Urea Nitrogen at Month 3
timeFrame: Baseline, month 3
measure: Change From Baseline in Blood Urea Nitrogen at Month 6
timeFrame: Baseline, month 6
measure: Change From Baseline in Blood Urea Nitrogen at Month 12
timeFrame: baseline, month 12
measure: Change From Baseline in Calcium at Month 1
timeFrame: baseline. month 1
measure: Change From Baseline in Calcium at Month 3
timeFrame: Baseline, month 3
measure: Change From Baseline in Calcium at Month 6
timeFrame: baseline, month 6
measure: Change From Baseline in Calcium at Month 12
timeFrame: Baseline, month 12
measure: Change From Baseline in Calcium (Corrected) at Month 1
timeFrame: Baseline, month 1
measure: Change From Baseline in Calcium (Corrected) at Month 3
timeFrame: baseline, month 3
measure: Change From Baseline in Calcium (Corrected) at Month 6
timeFrame: Baseline, Month 6
measure: Change From Baseline in Calcium (Corrected) at Month 12
timeFrame: Baselien, Month 12
measure: Change From Baseline in Chloride at Month 1
timeFrame: baseline, month 1
measure: Change From Baseline in Chloride at Month 3
timeFrame: Baseline, month 3
measure: Change From Baseline in Chloride at Month 6
timeFrame: Baseline, month 6
measure: Change From Baseline in Chloride at Month 12
timeFrame: Baseline, month 12
measure: Change From Baseline in Creatinine at Month 1
timeFrame: Baseline, month 1
measure: Change From Baseline in Creatinine at Month 3
timeFrame: Baseline, month 3
measure: Change From Baseline in Creatinine at Month 6
timeFrame: Baseline, month 6
measure: Change From Baseline in Creatinine at Month 12
timeFrame: Baseline, month 12
measure: Change From Baseline in Gamma-Glutamyl Transferase at Month 1
timeFrame: Baseline, month 1
measure: Change From Baseline in Gamma-Glutamyl Transferase at Month 3
timeFrame: Baseline, month 3
measure: Change From Baseline in Gamma-Glutamyl Transferase at Month 6
timeFrame: Baseline, month 6
measure: Change From Baseline in Gamma-Glutamyl Transferase at Month 12
timeFrame: Baseline, month 12
measure: Change From Baseline in Glucose at Month 1
timeFrame: Baseline, month 1
measure: Change From Baseline in Glucose at Month 3
timeFrame: Baseline, month 3
measure: Change From Baseline in Glucose at Month 6
timeFrame: Baseline, month 6
measure: Change From Baseline in Glucose at Month 12
timeFrame: baseline, month 12
measure: Change From Baseline in Potassium at Month 1
timeFrame: Baseline, month 1
measure: Change From Baseline in Potassium at Month 3
timeFrame: Baseline, month 3
measure: Change From Baseline in Potassium at Month 6
timeFrame: Baseline, month 6
measure: Change From Baseline in Potassium at Month 12
timeFrame: Baseline, month 12
measure: Change From Baseline in Magnesium at Month 1
timeFrame: Baseline, month 1
measure: Change From Baseline in Magnesium at Month 3
timeFrame: Baseline, month 3
measure: Change From Baseline in Magnesium at Month 6
timeFrame: Baseline, month 6
measure: Change From Baseline in Magnesium at Month 12
timeFrame: Baseline, month 12
measure: Change From Baseline in Sodium at Month 1
timeFrame: Baseline, month 1
measure: Change From Baseline in Sodium at Month 3
timeFrame: Baseline, Month 3
measure: Change From Baseline in Sodium at Month 6
timeFrame: Baseline, month 6
measure: Change From Baseline in Sodium at Month 12
timeFrame: Baseline, month 12
measure: Change From Baseline in Phosphorus at Month 1
timeFrame: Baseline, month 1
measure: Change From Baseline in Phosphorus at Month 3
timeFrame: Baseline, month 3
measure: Change From Baseline in Phosphorus at Month 6
timeFrame: Baseline, month 6
measure: Change From Baseline in Phosphorus at Month 12
timeFrame: Baseline, month 12
measure: Change From Baseline in Total Protein at Month 1
timeFrame: Baseline, month 1
measure: Change From Baseline in Total Protein at Month 3
timeFrame: Baseline, month 3
measure: Change From Baseline in Total Protein at Month 6
timeFrame: Baseline, month 6
measure: Change From Baseline in Total Protein at Month 12
timeFrame: Baseline, month 12
measure: Change From Baseline in Aspartate Amino Transferase at Month 1
timeFrame: Baseline, month 1
measure: Change From Baseline in Aspartate Amino Transferase at Month 3
timeFrame: Baseline, month 3
measure: Change From Baseline in Aspartate Amino Transferase
timeFrame: Baseline, month 6
measure: Change From Baseline in Aspartate Amino Transferase at Month 12
timeFrame: Baseline, month 12
measure: Change From Baseline in Alanine Amino Transferase at Month 1
timeFrame: Baseline, month 1
measure: Change From Baseline in Alanine Amino Transferase at Month 3
timeFrame: Baseline, month 3
measure: Change From Baseline in Alanine Amino Transferase at Month 6
timeFrame: Baseline, month 6
measure: Change From Baseline in Alanine Amino Transferase at Month 12
timeFrame: Baseline, month 12
measure: Change From Baseline in Basophils at Month 1
timeFrame: baseline, month 1
measure: Change From Baseline in Basophils at Month 3
timeFrame: Baseline, month 3
measure: Change From Baseline in Basophils at Month 6
timeFrame: Baseline, month 6
measure: Change From Baseline in Basophils at Month 12
timeFrame: Baseline, month 12
measure: Change From Baseline in Eosinophils at Month 1
timeFrame: Baseline, month 1
measure: Change From Baseline in Eosinophils at Month 3
timeFrame: Baseline, month 3
measure: Change From Baseline in Eosinophils at Month 6
timeFrame: Baseline, month 6
measure: Change From Baseline in Eosinophils at Month 12
timeFrame: Baseline, month 12
measure: Change From Baseline in Hematocrit at Month 1
timeFrame: Baseline, month 1
measure: Change From Baseline in Hematocrit at Month 3
timeFrame: Baseline, month 3
measure: Change From Baseline in Hematocrit at Month 6
timeFrame: Baseline, month 6
measure: Change From Baseline in Hematocrit at Month 12
timeFrame: Baseline, month 12
measure: Change From Baseline in Hemoglobin at Month 1
timeFrame: Baseline, month 1
measure: Change From Baseline in Hemoglobin at Month 3
timeFrame: Baseline, month 3
measure: Change From Baseline in Hemoglobin at Month 6
timeFrame: Baseline, month 6
measure: Change From Baseline in Hemoglobin at Month 12
timeFrame: Baseline, month 12
measure: Change From Baseline in Lymphocytes at Month 1
timeFrame: Baseline, month 1
measure: Change From Baseline in Lymphocytes at Month 3
timeFrame: Baseline, month 3
measure: Change From Baseline in Lymphocytes at Month 6
timeFrame: Baseline, month 6
measure: Change From Baseline in Lymphocytes at Month 12
timeFrame: Baseline, month 12
measure: Change From Baseline in Monocytes at Month 1
timeFrame: Baseline, month 1
measure: Change From Baseline in Monocytes at Month 3
timeFrame: Baseline, month 3
measure: Change From Baseline in Monocytes at Month 6
timeFrame: Baseline, month 6
measure: Change From Baseline in Monocytes at Month 12
timeFrame: Baseline, month 12
measure: Change From Baseline in Total Neutrophils at Month 1
timeFrame: Baseline, month 1
measure: Change From Baseline in Total Neutrophils at Month 3
timeFrame: Baseline, month 3
measure: Change From Baseline in Total Neutrophils at Month 6
timeFrame: Baseline, month 6
measure: Change From Baseline in Total Neutrophils at Month 12
timeFrame: Baseline, month 12
measure: Change From Baseline in Platelets at Month 1
timeFrame: Baseline, month 1
measure: Change From Baseline in Platelets at Month 3
timeFrame: Baseline, month 3
measure: Change From Baseline in Platelets at Month 6
timeFrame: Baseline, month 6
measure: Change From Baseline in Platelets at Month 12
timeFrame: Baseline, month 12
measure: Change From Baseline in Red Blood Cells at Month 1
timeFrame: Baseline, month 1
measure: Change From Baseline in Red Blood Cells at Month 3
timeFrame: Baseline, month 3
measure: Change From Baseline in Red Blood Cells at Month 6
timeFrame: Baseline, month 6
measure: Change From Baseline in Red Blood Cells at Month 12
timeFrame: Baseline, month 12
measure: Change From Baseline in White Blood Cells at Month 1
timeFrame: Baseline, month 1
measure: Change From Baseline in White Blood Cells at Month 3
timeFrame: Baseline, month 3
measure: Change From Baseline in White Blood Cells at Month 6
timeFrame: Baseline, month 6
measure: Change From Baseline in White Blood Cells at Month 12
timeFrame: Baseline, month 12
measure: Number of Participants With Laboratory Common Terminology Criteria for Adverse Events (CTCAE) Grade Greater or Equal to 3
timeFrame: Month 1, month 3, month 6, month 12
Other outcomes:
Locations:
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References:
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.
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.
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.
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.