Phase 2
N=227
Efficacy, Safety and Tolerability of Denosumab in the Treatment of Rheumatoid Arthritis
Rheumatoid Arthritis
Bottom Line
View on ClinicalTrials.gov: NCT00095498 ↗Enrolled (actual)
227
Serious AEs
6.4%
Results posted
Jan 2014
Primary outcome: Primary: Change From Baseline in Rheumatoid Arthritis Erosion Score Measured From MRI Assessments (RA-MRI ES) at Month 6 — 0.00; 0.00; 0.49 units on a scale — p=0.264
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- placebo (Drug); denosumab (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Amgen
- Primary completion
- Apr 2007
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change From Baseline in Rheumatoid Arthritis Erosion Score Measured From MRI Assessments (RA-MRI ES) at Month 6 |
0.00; 0.00; 0.49 | 0.264 |
| SECONDARY Change From Baseline in Radiographic Total Modified Sharp Score (TSS) at Month 12 |
0; 0; 0.5 | 0.032 sig |
| SECONDARY Change From Baseline in Radiographic Total Modified Sharp Score (TSS) at Month 6 |
0; 0; 0 | 0.602 |
| SECONDARY Change From Baseline in Radiographic Erosion Score at Month 12 |
0; 0; 0 | 0.012 sig |
| SECONDARY Change From Baseline in Radiographic Erosion Score at Month 6 |
0; 0; 0 | 0.277 |
| SECONDARY Change From Baseline in Radiographic Joint Space Narrowing Score at Month 12 |
0; 0; 0 | 0.382 |
| SECONDARY Change From Baseline in Radiographic Joint Space Narrowing Score at Month 6 |
0; 0; 0 | 0.236 |
| SECONDARY Percent Change From Baseline in Lumbar Spine Bone Mineral Density at Month 1 |
0.25; 0.59; -0.34 | 0.026 sig |
| SECONDARY Percent Change From Baseline in Lumbar Spine Bone Mineral Density at Month 6 |
2.61; 2.40; 0.73 | 0.002 sig |
| SECONDARY Percent Change From Baseline in Lumbar Spine Bone Mineral Density at Month 12 |
4.09; 3.00; 0.80 | <0.001 sig |
| SECONDARY Percent Change From Baseline in Femoral Neck Bone Mineral Density at Month 1 |
0.64; -0.15; -0.16 | 0.986 |
| SECONDARY Percent Change From Baseline in Femoral Neck Bone Mineral Density at Month 6 |
0.84; 0.89; -0.06 | 0.073 |
| SECONDARY Percent Change From Baseline in Femoral Neck Bone Mineral Density at Month 12 |
1.51; 1.34; -0.47 | 0.007 sig |
| SECONDARY Percent Change From Baseline in Total Hip Bone Mineral Density at Month 1 |
0.06; 0.00; -0.02 | 0.938 |
| SECONDARY Percent Change From Baseline in Total Hip Bone Mineral Density at Month 6 |
1.12; 0.95; -0.06 | 0.004 sig |
| SECONDARY Percent Change From Baseline in Total Hip Bone Mineral Density at Month 12 |
1.67; 1.56; -0.38 | <0.001 sig |
| SECONDARY Percent Change From Baseline in Serum Collagen C-Telopeptide (CTX) at Month 3 |
-78.67; -80.46; -11.48 | <0.001 sig |
| SECONDARY Percent Change From Baseline in Serum CTX at Month 6 |
-62.69; -50.64; -12.94 | <0.001 sig |
| SECONDARY Percent Change From Baseline in Serum CTX at Month 12 |
-65.65; -47.24; -23.36 | <0.001 sig |
| SECONDARY Percent Change From Baseline in Procollagen 1 N-terminal Peptide (P1NP) at Month 3 |
-55.08; -57.57; -12.23 | <0.001 sig |
| SECONDARY Percent Change From Baseline in P1NP at Month 6 |
-57.06; -51.57; -22.17 | <0.001 sig |
| SECONDARY Percent Change From Baseline in P1NP at Month 12 |
-45.84; -41.8; -17.53 | 0.016 sig |
| SECONDARY Percent Change From Baseline in Urine Type II Collagen C-telopeptide (C-Tx) /Creatinine at Month 3 |
-46.59; -35.8; 2.71 | <0.001 sig |
| SECONDARY Percent Change From Baseline in Urine Type II C-Tx /Creatinine at Month 6 |
7.17; 9.65; 4.54 | 0.673 |
| SECONDARY Percent Change From Baseline in Urine Type II C-Tx /Creatinine at Month 12 |
36.92; 61.92; -3.93 | 0.175 |
| SECONDARY Number of Participants With Anti-Denosumab Binding Antibodies |
4; 0; 2 | — |
| SECONDARY Number of Participants With Anti-Denosumab Binding Antibody and Neutralizing Antibody |
0; 0 | — |
| SECONDARY Change From Baseline in Albumin at Month 1 |
-0.36; -0.24; -0.30 | — |
| SECONDARY Change From Baseline in Albumin at Month 3 |
-0.30; -0.12; -0.18 | — |
| SECONDARY Change From Baseline in Albumin at Month 6 |
-0.30; -0.90; -0.77 | — |
| SECONDARY Change From Baseline in Albumin at Month 12 |
-0.13; -0.06; -0.59 | — |
| SECONDARY Change From Baseline in Alkaline Phosphatase at Month 1 |
-5.87; -3.66; 1.18 | — |
| SECONDARY Change From Baseline in Alkaline Phosphatase at Month 3 |
-13.27; -12.38; -2.03 | — |
| SECONDARY Change From Baseline in Alkaline Phosphatase at Month 6 |
-7.84; -12.49; -0.54 | — |
| SECONDARY Change From Baseline in Alkaline Phosphatase at Month 12 |
-11.92; -11.34; -4.63 | — |
| SECONDARY Change From Baseline in Bicarbonate at Month 1 |
0.78; 0.06; 0.54 | — |
| SECONDARY Change From Baseline in Bicarbonate at Month 3 |
0.12; 0.39; -0.67 | — |
| SECONDARY Change From Baseline in Bicarbonate at Month 6 |
0.45; -0.12; -0.18 | — |
| SECONDARY Change From Baseline in Bicarbonate at Month 12 |
0.81; 0.58; 0.23 | — |
| SECONDARY Change From Baseline in Total Bilirubin at Month 1 |
0.26; -0.23; 0.42 | — |
| SECONDARY Change From Baseline in Total Bilirubin at Month 3 |
0.92; -0.23; 0.44 | — |
| SECONDARY Change From Baseline in Total Bilirubin at Month 6 |
1.08; -0.61; 0.34 | — |
| SECONDARY Change From Baseline in Total Bilirubin at Month 12 |
0.41; -0.35; 0.03 | — |
| SECONDARY Change From Baseline in Blood Urea Nitrogen at Month 1 |
0; 0.15; -0.01 | — |
| SECONDARY Change From Baseline in Blood Urea Nitrogen at Month 3 |
0.04; 0.41; 0.06 | — |
| SECONDARY Change From Baseline in Blood Urea Nitrogen at Month 6 |
-0.21; -0.08; -0.04 | — |
| SECONDARY Change From Baseline in Blood Urea Nitrogen at Month 12 |
0.32; 0.24; -0.09 | — |
| SECONDARY Change From Baseline in Calcium at Month 1 |
-0.05; -0.05; 0.01 | — |
| SECONDARY Change From Baseline in Calcium at Month 3 |
-0.01; -0.02; 0 | — |
| SECONDARY Change From Baseline in Calcium at Month 6 |
-0.01; -0.03; -0.01 | — |
| SECONDARY Change From Baseline in Calcium at Month 12 |
-0.01; 0.01; 0.01 | — |
| SECONDARY Change From Baseline in Calcium (Corrected) at Month 1 |
-0.05; -0.05; 0.01 | — |
| SECONDARY Change From Baseline in Calcium (Corrected) at Month 3 |
-0.01; -0.02; 0 | — |
| SECONDARY Change From Baseline in Calcium (Corrected) at Month 6 |
-0.01; -0.02; -0.01 | — |
| SECONDARY Change From Baseline in Calcium (Corrected) at Month 12 |
-0.01; 0.01; 0 | — |
| SECONDARY Change From Baseline in Chloride at Month 1 |
0.24; 0.58; 0.01 | — |
| SECONDARY Change From Baseline in Chloride at Month 3 |
-0.01; 0.38; 0.78 | — |
| SECONDARY Change From Baseline in Chloride at Month 6 |
-0.57; 0.48; 0 | — |
| SECONDARY Change From Baseline in Chloride at Month 12 |
-0.62; -0.21; -0.08 | — |
| SECONDARY Change From Baseline in Creatinine at Month 1 |
-0.88; 0.38; 1.47 | — |
| SECONDARY Change From Baseline in Creatinine at Month 3 |
0.62; 3.20; 3.81 | — |
| SECONDARY Change From Baseline in Creatinine at Month 6 |
3.30; 3.84; 3.54 | — |
| SECONDARY Change From Baseline in Creatinine at Month 12 |
5.44; 4.42; 3.73 | — |
| SECONDARY Change From Baseline in Gamma-Glutamyl Transferase at Month 1 |
1.04; -1.25; 0.26 | — |
| SECONDARY Change From Baseline in Gamma-Glutamyl Transferase at Month 3 |
2.32; 0.04; 1.51 | — |
| SECONDARY Change From Baseline in Gamma-Glutamyl Transferase at Month 6 |
7.37; 0.28; 5.67 | — |
| SECONDARY Change From Baseline in Gamma-Glutamyl Transferase at Month 12 |
2.98; 1.08; -1.38 | — |
| SECONDARY Change From Baseline in Glucose at Month 1 |
0.06; 0.20; 0.05 | — |
| SECONDARY Change From Baseline in Glucose at Month 3 |
0.08; 0.20; 0.04 | — |
| SECONDARY Change From Baseline in Glucose at Month 6 |
0.12; 0.20; -0.05 | — |
| SECONDARY Change From Baseline in Glucose at Month 12 |
-0.04; 0.22; 0.19 | — |
| SECONDARY Change From Baseline in Potassium at Month 1 |
0.06; 0.06; 0.04 | — |
| SECONDARY Change From Baseline in Potassium at Month 3 |
-0.01; 0.06; 0.04 | — |
| SECONDARY Change From Baseline in Potassium at Month 6 |
0.01; -0.01; 0 | — |
| SECONDARY Change From Baseline in Potassium at Month 12 |
-0.07; -0.08; -0.04 | — |
| SECONDARY Change From Baseline in Magnesium at Month 1 |
0.01; 0.02; 0.01 | — |
| SECONDARY Change From Baseline in Magnesium at Month 3 |
-0.01; 0.02; 0 | — |
| SECONDARY Change From Baseline in Magnesium at Month 6 |
0; 0.01; 0.01 | — |
| SECONDARY Change From Baseline in Magnesium at Month 12 |
-0.01; -0.01; -0.01 | — |
| SECONDARY Change From Baseline in Sodium at Month 1 |
-0.03; -0.06; 0.33 | — |
| SECONDARY Change From Baseline in Sodium at Month 3 |
-0.14; -0.16; 0.39 | — |
| SECONDARY Change From Baseline in Sodium at Month 6 |
-0.12; -0.06; 0.03 | — |
| SECONDARY Change From Baseline in Sodium at Month 12 |
-0.25; -0.27; 0.33 | — |
| SECONDARY Change From Baseline in Phosphorus at Month 1 |
-0.09; -0.06; 0.02 | — |
| SECONDARY Change From Baseline in Phosphorus at Month 3 |
-0.03; -0.03; 0.01 | — |
| SECONDARY Change From Baseline in Phosphorus at Month 6 |
-0.05; -0.01; 0.03 | — |
| SECONDARY Change From Baseline in Phosphorus at Month 12 |
-0.05; 0; 0 | — |
| SECONDARY Change From Baseline in Total Protein at Month 1 |
-0.46; -0.40; 0.21 | — |
| SECONDARY Change From Baseline in Total Protein at Month 3 |
-0.29; 0.07; -0.20 | — |
| SECONDARY Change From Baseline in Total Protein at Month 6 |
-0.09; -0.62; -0.57 | — |
| SECONDARY Change From Baseline in Total Protein at Month 12 |
-0.97; -0.91; -0.98 | — |
| SECONDARY Change From Baseline in Aspartate Amino Transferase at Month 1 |
-0.79; -0.26; 0.90 | — |
| SECONDARY Change From Baseline in Aspartate Amino Transferase at Month 3 |
1.99; 0.40; 2.69 | — |
| SECONDARY Change From Baseline in Aspartate Amino Transferase |
3.85; 0.87; 3.24 | — |
| SECONDARY Change From Baseline in Aspartate Amino Transferase at Month 12 |
3.86; 3.75; 2.24 | — |
| SECONDARY Change From Baseline in Alanine Amino Transferase at Month 1 |
-1.84; -1.03; 1.20 | — |
| SECONDARY Change From Baseline in Alanine Amino Transferase at Month 3 |
0.04; -2.10; 1.54 | — |
| SECONDARY Change From Baseline in Alanine Amino Transferase at Month 6 |
1.20; -1.76; 5.44 | — |
| SECONDARY Change From Baseline in Alanine Amino Transferase at Month 12 |
4.86; 1.66; 1.82 | — |
| SECONDARY Change From Baseline in Basophils at Month 1 |
0; 0; -0.01 | — |
| SECONDARY Change From Baseline in Basophils at Month 3 |
-0.01; -0.01; -0.01 | — |
| SECONDARY Change From Baseline in Basophils at Month 6 |
0; 0; 0 | — |
| SECONDARY Change From Baseline in Basophils at Month 12 |
0.02; 0; 0.03 | — |
| SECONDARY Change From Baseline in Eosinophils at Month 1 |
-0.02; -0.01; 0.01 | — |
| SECONDARY Change From Baseline in Eosinophils at Month 3 |
0; 0; -0.01 | — |
| SECONDARY Change From Baseline in Eosinophils at Month 6 |
-0.03; 0; 0 | — |
| SECONDARY Change From Baseline in Eosinophils at Month 12 |
0.03; 0.02; 0.01 | — |
| SECONDARY Change From Baseline in Hematocrit at Month 1 |
0; 0; 0 | — |
| SECONDARY Change From Baseline in Hematocrit at Month 3 |
0.01; 0; 0 | — |
| SECONDARY Change From Baseline in Hematocrit at Month 6 |
0.01; 0; 0 | — |
| SECONDARY Change From Baseline in Hematocrit at Month 12 |
0; 0; -0.01 | — |
| SECONDARY Change From Baseline in Hemoglobin at Month 1 |
-0.33; -1.48; -0.69 | — |
| SECONDARY Change From Baseline in Hemoglobin at Month 3 |
0.69; -1.02; -1.10 | — |
| SECONDARY Change From Baseline in Hemoglobin at Month 6 |
-0.36; -1.69; -0.69 | — |
| SECONDARY Change From Baseline in Hemoglobin at Month 12 |
1.21; 0.02; -0.46 | — |
| SECONDARY Change From Baseline in Lymphocytes at Month 1 |
-0.02; 0.10; 0 | — |
| SECONDARY Change From Baseline in Lymphocytes at Month 3 |
0.07; 0.14; 0.08 | — |
| SECONDARY Change From Baseline in Lymphocytes at Month 6 |
0.12; 0.05; 0.03 | — |
| SECONDARY Change From Baseline in Lymphocytes at Month 12 |
-0.02; 0.04; -0.02 | — |
| SECONDARY Change From Baseline in Monocytes at Month 1 |
0.01; -0.01; 0.01 | — |
| SECONDARY Change From Baseline in Monocytes at Month 3 |
0.02; 0.01; 0.02 | — |
| SECONDARY Change From Baseline in Monocytes at Month 6 |
0.05; 0.04; 0.04 | — |
| SECONDARY Change From Baseline in Monocytes at Month 12 |
0.03; 0; 0.02 | — |
| SECONDARY Change From Baseline in Total Neutrophils at Month 1 |
0; 0.18; -0.13 | — |
| SECONDARY Change From Baseline in Total Neutrophils at Month 3 |
0.11; 0.26; -0.11 | — |
| SECONDARY Change From Baseline in Total Neutrophils at Month 6 |
0.18; -0.05; 0.27 | — |
| SECONDARY Change From Baseline in Total Neutrophils at Month 12 |
0.65; 0.04; 0.10 | — |
| SECONDARY Change From Baseline in Platelets at Month 1 |
1.78; 10.36; 2.96 | — |
| SECONDARY Change From Baseline in Platelets at Month 3 |
-2.82; 6.86; -1.97 | — |
| SECONDARY Change From Baseline in Platelets at Month 6 |
1.95; 1.00; 1.57 | — |
| SECONDARY Change From Baseline in Platelets at Month 12 |
3.32; -4.26; 1.07 | — |
| SECONDARY Change From Baseline in Red Blood Cells at Month 1 |
-0.01; -0.01; -0.01 | — |
| SECONDARY Change From Baseline in Red Blood Cells at Month 3 |
0.05; 0.02; 0 | — |
| SECONDARY Change From Baseline in Red Blood Cells at Month 6 |
0.01; -0.04; 0.01 | — |
| SECONDARY Change From Baseline in Red Blood Cells at Month 12 |
0.01; -0.06; -0.03 | — |
| SECONDARY Change From Baseline in White Blood Cells at Month 1 |
-0.03; 0.26; -0.10 | — |
| SECONDARY Change From Baseline in White Blood Cells at Month 3 |
0.18; 0.40; -0.05 | — |
| SECONDARY Change From Baseline in White Blood Cells at Month 6 |
0.30; 0.04; 0.35 | — |
| SECONDARY Change From Baseline in White Blood Cells at Month 12 |
0.70; 0.11; 0.13 | — |
| SECONDARY Number of Participants With Laboratory Common Terminology Criteria for Adverse Events (CTCAE) Grade Greater or Equal to 3 |
0; 0; 1; 0; 1; 0 | — |
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.
Data sourced from ClinicalTrials.gov (NCT00095498). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.