Phase 3
Completed N=58
A Study of Tocilizumab in Combination With Disease-Modifying Anti-Rheumatic Drugs (DMARDs) in Participants With Moderate to Severe Active Rheumatoid Arthritis With an Inadequate Response to DMARDs
Source: ClinicalTrials.gov NCT00996606 ↗Enrolled (actual)
58
Serious AEs
8.6%
Results posted
Nov 2016
Primary outcomePrimary: Change From Baseline to Week 4 in Synovitis of the Wrist According to Rheumatoid Arthritis Magnetic Resonance Imaging (RAMRIS) Score — 5.78; -0.88 units on a scale
◆ Published Evidence
No publication linked
No peer-reviewed publication reporting this trial's results has been linked yet. This can indicate results are unpublished — a known publication-bias signal. We re-check periodically.
Summary
This open-label, single-arm study will evaluate the efficacy and safety of tocilizumab in combination with DMARDs in participants with moderate to severe active rheumatoid arthritis who have an inadequate response to DMARDs. Participants will receive tocilizumab as 8 milligrams per kilogram (mg/kg) via intravenous (IV) infusion every 4 weeks in addition to their current DMARD therapy.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change From Baseline to Week 4 in Synovitis of the Wrist According to Rheumatoid Arthritis Magnetic Resonance Imaging (RAMRIS) Score |
5.78; -0.88 | — |
| PRIMARY Change From Baseline to Week 4 in Synovitis of the Wrist According to Relative Enhancement (RE) Before and After Contrast Injection |
99.25; -0.48 | — |
| PRIMARY Change From Baseline to Week 4 in Synovitis of the Wrist According to Rate of Early Enhancement (REE) Per Second Before and After Contrast Injection |
1.19; -0.10 | — |
| SECONDARY Change From Baseline to Weeks 2, 12, 24, and 48 in Synovitis of the Wrist According to RAMRIS Score |
-0.44; -1.28; -1.94; -1.60 | — |
| SECONDARY Change From Baseline to Weeks 2, 12, 24, and 48 in Synovitis of the Wrist According to RE Before and After Contrast Injection |
5.80; -9.27; -26.48; -19.74 | — |
| SECONDARY Change From Baseline to Weeks 2, 12, 24, and 48 in Synovitis of the Wrist According to REE Per Second Before and After Contrast Injection |
-0.04; -0.48; -0.57; -0.66 | — |
| SECONDARY Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Synovitis of the Wrist and Metacarpo-Phalangeal (MCP) Joints According to Modified RAMRIS Score |
5.04; -0.02; -0.20; -0.47; -1.06; -1.23 | — |
| SECONDARY Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Number of Bones With Erosion in the Wrist and MCP Joints |
8.07; -0.26; -0.16; -0.14; -0.06; -0.04 | — |
| SECONDARY Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Erosion of the Wrist and MCP Joints According to RAMRIS Score |
7.32; -0.24; -0.16; 0.08; 0.28; 0.34 | — |
| SECONDARY Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Number of Bones With Bone Marrow Edema in the Wrist and MCP Joints |
7.91; -0.57; -0.78; -1.80; -2.56; -3.56 | — |
| SECONDARY Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Bone Marrow Edema of the Wrist and MCP Joints According to RAMRIS Score |
13.11; -0.61; -0.68; -3.02; -4.94; -6.45 | — |
| SECONDARY Change From Baseline to Weeks 24 and 48 in Total Modified Sharp Score (TMSS), Erosion Score (ES), and Joint Space Narrowing Score (JSNS) |
18.25; 0.41; 1.46; 4.78; 0.05; 0.31 | — |
| SECONDARY Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Ritchie Articular Index Score |
16.69; -4.85; -7.06; -9.37; -11.60; -12.09 | — |
| SECONDARY Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Perceived Pain According to Visual Analog Scale (VAS) Score |
57.69; -18.56; -20.57; -32.75; -35.36; -39.44 | — |
| SECONDARY Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Perceived General Health According to VAS Score |
59.51; -19.58; -19.73; -32.64; -36.55; -40.41 | — |
| SECONDARY Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Health Assessment Questionnaire Disability Index (HAQ-DI) Score |
1.33; -0.34; -0.35; -0.52; -0.61; -0.67 | — |
| SECONDARY Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Disease Activity Score of 28 Joints (DAS28) Score |
5.44; -1.22; -1.62; -2.29; -2.88; -3.07 | — |
| SECONDARY Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Vascular Endothelial Growth Factor (VEGF) Concentration |
154.37; -53.06; -63.61; -36.33; -66.10; -29.35 | — |
| SECONDARY Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Erythrocyte Sedimentation Rate (ESR) |
37.39; -27.30; -27.63; -28.75; -30.58; -27.22 | — |
| SECONDARY Change From Baseline to Weeks 2, 4, 12, 24, and 48 in High-Sensitivity C-Reactive Protein (hsCRP) Concentration |
14.43; -13.44; -11.96; -11.56; -13.43; -10.49 | — |
| SECONDARY Change From Baseline to Weeks 2 and 4 in Soluble Interleukin-6 Receptor (sIL6R) Level |
45270.8; 332597.2; 303037.2 | — |
| SECONDARY Change From Baseline to Weeks 2 and 4 in Messenger Ribonucleic Acid (mRNA) for Interleukin (IL)-17 (2^Delta Cycle Threshold [ΔCt]) Level |
0.0; 0.0; 0.0 | — |
| SECONDARY Change From Baseline to Weeks 2 and 4 in mRNA for IL-23 Receptor (2^ΔCt) Level |
0.224; -0.007; 0.015 | — |
| SECONDARY Change From Baseline to Weeks 2 and 4 in mRNA for RAR-Related Orphan Receptor (ROR)-γT (2^ΔCt) Level |
0.083; -0.027; -0.004 | — |
| SECONDARY Change From Baseline to Weeks 2 and 4 in mRNA for Forkhead Box Protein (FOXP) 3 (2^ΔCt) Level |
1.035; -0.315; -0.059 | — |
| SECONDARY Change From Baseline to Weeks 2 and 4 in Cluster of Differentiation (CD) 4-Positive Cells as a Percentage of Peripheral Blood Mononuclear Cells (PBMCs) |
56.15; -1.47; 0.77 | — |
| SECONDARY Change From Baseline to Weeks 2 and 4 in CD4 Mean Intensity of Fluorescence |
6970.94; 464.04; -1139.29 | — |
| SECONDARY Change From Baseline to Weeks 2 and 4 in CD25-Positive Cells as a Percentage of PBMCs |
7.27; -0.95; 0.04 | — |
| SECONDARY Change From Baseline to Weeks 2 and 4 in CD25 Mean Intensity of Fluorescence |
2326.25; 74.76; 162.27 | — |
| SECONDARY Change From Baseline to Weeks 2 and 4 in CD45 "RO" Isoform (RO)-Positive Cells as a Percentage of PBMCs |
37.16; 1.77; 3.06 | — |
| SECONDARY Change From Baseline to Weeks 2 and 4 in CD45RO Mean Intensity of Fluorescence |
5138.47; -1779.59; -131.75 | — |
| SECONDARY Change From Baseline to Weeks 2 and 4 in Cysteine-Cysteine Chemokine Receptor (CCR) 6-Positive Cells as a Percentage of PBMCs |
12.75; 2.34; 3.09 | — |
| SECONDARY Change From Baseline to Weeks 2 and 4 in CCR6 Mean Intensity of Fluorescence |
4651.85; 291.63; 376.56 | — |
| SECONDARY Change From Baseline to Weeks 2 and 4 in CCR4-Positive Cells as a Percentage of PBMCs |
11.79; -1.64; 0.35 | — |
| SECONDARY Change From Baseline to Weeks 2 and 4 in CCR4 Mean Intensity of Fluorescence |
2534.67; 262.95; 273.19 | — |
| SECONDARY Change From Baseline to Weeks 2 and 4 in IL-23 Receptor p19 Subunit (IL-23Rp19)-Positive Cells as a Percentage of PBMCs |
1.10; -0.32; -0.34 | — |
| SECONDARY Change From Baseline to Weeks 2 and 4 in IL-23Rp19 Mean Intensity of Fluorescence |
1416.30; 284.42; 82.88 | — |
| SECONDARY Change From Baseline to Weeks 2 and 4 in Regulatory T (Treg) Cells as a Percentage of PBMCs |
2.03; -0.07; 0.35 | — |
| SECONDARY Change From Baseline to Weeks 2 and 4 in Treg Cells as a Percentage of T Cells |
2.42; -0.19; 0.44 | — |
| SECONDARY Change From Baseline to Weeks 2 and 4 in Treg Cell Level |
34.51; 1.25; 6.30 | — |
| SECONDARY Change From Baseline to Weeks 2 and 4 in Helper T (Th) 17 Cells as a Percentage of PBMCs |
0.024; 0.006; -0.002 | — |
| SECONDARY Change From Baseline to Weeks 2 and 4 in Th17 Cells as a Percentage of T Cells |
0.031; -0.003; -0.007 | — |
| SECONDARY Change From Baseline to Weeks 2 and 4 in Th17 Cell Level |
0.295; 0.050; -0.068 | — |
| SECONDARY Change From Baseline to Weeks 2 and 4 in CD19-Positive Cells as a Percentage of PBMCs |
8.40; -4.80; -0.12 | — |
| SECONDARY Change From Baseline to Weeks 2 and 4 in CD19 Mean Intensity of Fluorescence |
19268.58; -3656.00; 251.34 | — |
| SECONDARY Change From Baseline to Weeks 2 and 4 in CD24-Positive Cells as a Percentage of PBMCs |
8.02; -4.90; -0.73 | — |
| SECONDARY Change From Baseline to Weeks 2 and 4 in CD24 Mean Intensity of Fluorescence |
3133.63; 1015.00; 436.05 | — |
| SECONDARY Change From Baseline to Weeks 2 and 4 in CD27-Positive Cells as a Percentage of PBMCs |
57.51; -12.40; 1.44 | — |
| SECONDARY Change From Baseline to Weeks 2 and 4 in CD27 Mean Intensity of Fluorescence |
1288.10; -349.00; -53.98 | — |
| SECONDARY Change From Baseline to Weeks 2 and 4 in CD38-Positive Cells as a Percentage of PBMCs |
49.51; -4.30; -0.78 | — |
| SECONDARY Change From Baseline to Weeks 2 and 4 in CD38 Mean Intensity of Fluorescence |
5746.98; -193.00; 162.66 | — |
| SECONDARY Change From Baseline to Weeks 2 and 4 in Immunoglobulin (Ig) M-Positive Cells as a Percentage of PBMCs |
17.06; -3.60; 1.19 | — |
| SECONDARY Change From Baseline to Weeks 2 and 4 in IgM Mean Intensity of Fluorescence |
15545.94; -10381.0; -56.45 | — |
| SECONDARY Change From Baseline to Weeks 2 and 4 in Mature B Cells as a Percentage of PBMCs |
4.72; -3.40; -0.35 | — |
| SECONDARY Change From Baseline to Weeks 2 and 4 in Mature B Cells as a Percentage of B Cells |
48.58; -9.40; -0.11 | — |
| SECONDARY Change From Baseline to Week 4 in Mature B Cell Level |
78.27; 2.29 | — |
| SECONDARY Change From Baseline to Weeks 2 and 4 in Memory B Cells as a Percentage of PBMCs |
1.49; -0.90; 0.13 | — |
| SECONDARY Change From Baseline to Weeks 2 and 4 in Memory B Cells as a Percentage of B Cells |
18.95; 4.30; 0.62 | — |
| SECONDARY Change From Baseline to Week 4 in Memory B Cell Level |
29.29; 2.85 | — |
| SECONDARY Change From Baseline to Weeks 2 and 4 in Transitional B Cells as a Percentage of PBMCs |
0.58; 0.00; -0.22 | — |
| SECONDARY Change From Baseline to Weeks 2 and 4 in Transitional B Cells as a Percentage of B Cells |
5.26; 5.80; -1.09 | — |
| SECONDARY Change From Baseline to Week 4 in Transitional B Cell Level |
6.70; -0.62 | — |
| SECONDARY Change From Baseline to Weeks 2 and 4 in Plasma B Cells as a Percentage of PBMCs |
0.22; 0.00; -0.08 | — |
| SECONDARY Change From Baseline to Weeks 2 and 4 in Plasma B Cells as a Percentage of B Cells |
1.52; -0.20; -0.06 | — |
| SECONDARY Change From Baseline to Week 4 in Plasma B Cell Level |
3.13; -1.11 | — |
| SECONDARY Change From Baseline to Weeks 2 and 4 in Th17 Cysteine-Cysteine Chemokine Ligand (CCL) 20 Level |
35.03; 2.57; -2.65 | — |
| SECONDARY Change From Baseline to Weeks 2 and 4 in Th17CCL17 Level |
456.02; 119.58; 75.84 | — |
| SECONDARY Change From Baseline to Weeks 2 and 4 in B Cell-Attracting Chemokine (BCA) Level |
122.28; -21.37; -18.26 | — |
| SECONDARY Change From Baseline to Weeks 2 and 4 in Stromal Cell-Derived Factor (SDF) 1 Level |
2151.47; -1.85; -26.46 | — |
| SECONDARY Change From Baseline to Weeks 2 and 4 in B Cell-Activating Factor (BAFF) Level |
802.98; 28.04; 36.17 | — |
| SECONDARY Change From Baseline to Weeks 2 and 4 in A Proliferation-Inducing Ligand (APRIL) Level |
6807.49; -816.13; 7.82 | — |
| SECONDARY Change From Baseline to Weeks 2 and 4 in Tumor Necrosis Factor (TNF)-α Level |
2.285; 0.077; 0.254 | — |
| SECONDARY Change From Baseline to Weeks 2 and 4 in IL-1β Level |
0.699; -0.160; -0.243 | — |
| SECONDARY Change From Baseline to Weeks 2 and 4 in IL-17 Level |
15.00; 0.00; 0.00 | — |
| SECONDARY Change From Baseline to Weeks 2 and 4 in Monocyte Chemoattractant Protein (MCaP)-1 Level |
343.86; 22.70; -33.20 | — |
| SECONDARY Change From Baseline to Weeks 2 and 4 in Osteocalcin Level |
14069.60; -616.34; -99.00 | — |
| SECONDARY Change From Baseline to Weeks 2 and 4 in Type I Collagen N-Propeptide Level |
7731.89; 842.65; -576.49 | — |
| SECONDARY Change From Baseline to Weeks 2 and 4 in C-Terminal Telopeptide (CTX)-1 Level |
487.28; 43.33; 48.80 | — |
| SECONDARY Change From Baseline to Weeks 2 and 4 in Type I Collagen C-Terminal Telopeptide (ICTP) Level |
6381.12; 306.60; 193.25 | — |
| SECONDARY Change From Baseline to Weeks 2 and 4 in Type II Collagen N-Propeptide (PIIANP) Level |
1329158; -37518.8; -69799.1 | — |
| SECONDARY Change From Baseline to Weeks 2 and 4 in Type II Collagen Helical Peptide (HELIX-II) Level |
2521.12; 126.02; -78.29 | — |
| SECONDARY Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Hemoglobin (Hb) Concentration |
128.28; 3.86; 2.09; 4.31; 6.23; 7.17 | — |
| SECONDARY Change From Baseline to Day 2 and Weeks 2 and 4 in Soluble Transferrin Receptor (STR) Concentration |
4536413; -83532.0; 15712.17; -89722.7 | — |
| SECONDARY Change From Baseline to Week 48 in Initial Rate of Enhancement (IRE) by DYNAMIKA Software Analysis |
0.00503; -0.00246 | — |
| SECONDARY Change From Baseline to Week 48 in Maximum Enhancement (ME) by DYNAMIKA Software Analysis |
1.606; -0.177 | — |
| SECONDARY Change From Baseline to Week 48 in Number of Enhancing Voxels (Ntotal) by DYNAMIKA Software Analysis |
3155.69; -974.16 | — |
| SECONDARY Change From Baseline to Week 48 in Number of Persistent Enhancing Voxels (Npersistent) by DYNAMIKA Software Analysis |
182.04; -0.53 | — |
| SECONDARY Change From Baseline to Week 48 in Number of Plateau Enhancing Voxels (Nplateau) by DYNAMIKA Software Analysis |
1839.63; -635.72 | — |
| SECONDARY Change From Baseline to Week 48 in Number of Washout Enhancing Voxels (Nwashout) by DYNAMIKA Software Analysis |
1167.16; -358.25 | — |
| SECONDARY Change From Baseline to Week 48 in Ntotal×IRE by DYNAMIKA Software Analysis |
6.01; -4.84 | — |
| SECONDARY Change From Baseline to Week 48 in Ntotal×ME by DYNAMIKA Software Analysis |
1882.40; -793.59 | — |
Eligibility Criteria
Inclusion Criteria
- Moderate to severe active RA of ≥6 months duration
- DAS28 >3.2
- Inadequate response to a stable dose of non-biologic DMARD for ≥2 months
- Those receiving oral corticosteroids must have been at stable dose for ≥25 days in the 28 days prior to first study treatment
Exclusion Criteria
- Rheumatic autoimmune disease other than RA
- History of or current inflammatory joint disease other than RA
- Previous treatment with alkylating agents or total lymphoid irradiation
- Intra-articular or parenteral corticosteroids within 6 weeks prior to Baseline
- Previous treatment with any cell-depleting therapies
- American College of Rheumatology (ACR) Functional Class IV
Data sourced from ClinicalTrials.gov (NCT00996606). 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. Informational only — not medical advice.