Phase 3
Completed N=378
A Study of Retreatment With MabThera (Rituximab) in Combination With Methotrexate in Patients With Rheumatoid Arthritis (RA)
Source: ClinicalTrials.gov NCT00422383 ↗Enrolled (actual)
378
Serious AEs
14.9%
Results posted
May 2015
Primary outcomePrimary: Percentage of Participants With a Response as Determined by American College of Rheumatology (ACR) 20% Improvement (ACR20) — 64.2; 63.9; 72.0 percentage of participants — p=0.8156
Summary
This study will evaluate the efficacy and safety of various treatment and retreatment regimens of MabThera. All patients will receive concomitant methotrexate, 10-25mg once weekly either orally or parenterally. The anticipated time on study treatment is 2+ years, and the target sample size is 100-500 individuals.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Participants With a Response as Determined by American College of Rheumatology (ACR) 20% Improvement (ACR20) |
64.2; 63.9; 72.0 | 0.8156 |
| SECONDARY Percentage of Participants With ACR 50% Improvement Criteria (ACR50) Response at Week 48 |
39; 39; 48 | — |
| SECONDARY Percentage of Participants With a ACR 70% Improvement Criteria (ACR70) Response at Week 48 |
20; 19; 23 | — |
| SECONDARY Disease Activity Score Based on 28-Joint Count and Erythrocyte Sedimentation Rate (DAS28-ESR): Adjusted Mean Change From BL at Week 48 |
-2.13; -2.19; -2.42 | 0.7127 |
| SECONDARY Percentage of Participants With a Response at Week 48 by European League Against Rheumatism (EULAR) Category |
26.9; 27.7; 10.8; 50.7; 55.5; 62.4 | 0.5029 |
| SECONDARY Change in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Score From BL at Week 48 |
6.605; 8.109; 8.364; 2.000; 6.192 | — |
| SECONDARY Short-Form 36 Health Survey (SF-36) Score |
31.657; 30.815; 30.319; 39.709; 38.875; 42.736 | — |
| SECONDARY Change in SF-36 Score From BL |
8.180; 7.914; 11.948; 9.815; 9.323; 12.712 | — |
| SECONDARY Maximum Observed Serum Concentrations Following the 1st Infusion of Rituximab (Cfirst) in the 1st and 2nd Courses of Treatment in Micrograms Per mL (µg/mL) |
165; 163; 317; 177; 345; 350 | — |
| SECONDARY Maximum Observed Serum Concentrations Following the 2nd Infusion of Rituximab (Csecond) in the 1st and 2nd Courses of Treatment in µg/mL |
194; 190; 373; 209; 380; 392 | — |
| SECONDARY Terminal Elimination Half-Life (t1/2) in the 1st and 2nd Courses of Treatment in Days |
16.04; 16.75; 17.67; 19.62; 22.13; 21.42 | — |
| SECONDARY Peripheral Cluster of Differentiation (CD) 19 Positive (+) B Cell Count at BL in Cells Per Microliter (Cells/µL) |
183.6; 168.9; 205.3; 318.2; 235.4 | — |
| SECONDARY Percentage of Participants With Peripheral CD19+ B Cell Counts Above BL or the Lower Limit of Normal (LLN) |
0.8; 0.0; 2.4; 0.0; 8.7; 0.0 | — |
| SECONDARY Peripheral CD20+ B Cell Count in Cells/µL |
184.8; 173.4; 218.1; 0.2; 0.2; 0.2 | — |
| SECONDARY Peripheral CD22+ B Cell Count in Cells/µL |
188.0; 177.1; 221.6; 24.5; 23.2; 29.0 | — |
| SECONDARY Peripheral CD19+CD27+ B Cell Count in Cells/µL |
41.4; 42.2; 42.3; 4.6; 5.1; 4.7 | — |
| SECONDARY Peripheral CD19+CD27 Negative (-) B Cell Count in Cells/µL |
141.1; 126.4; 179.3; 16.7; 15.2; 19.3 | — |
| SECONDARY Peripheral CD3+ T Cell Count in Cells/µL |
1262.1; 1229.6; 1319.7; 237.8; 263.4; 226.9 | — |
| SECONDARY Change From BL in Peripheral CD3+ T Cell Count |
-1000.6; -968.8; -1065.4; 25.2; 40.8; 34.0 | — |
| SECONDARY Peripheral CD4+ T Cell Count in Cells/µL |
900.4; 876.7; 953.6; 130.2; 145.9; 129.8 | — |
| SECONDARY Change From BL in Peripheral CD4+ T Cell Count |
-744.6; -738.1; -801.2; 24.3; 38.9; 36.0 | — |
| SECONDARY Peripheral CD8+ T Cell Count in Cells/µL |
361.8; 352.6; 364.9; 106.8; 118.6; 98.1 | — |
| SECONDARY Change From BL in Peripheral CD8+ Cell Count |
-256.2; -229.0; -262.3; -1.5; 2.6; -5.0 | — |
| SECONDARY Peripheral CD16+56+ Natural Killer (NK) Cell Count in Cells/µL |
172.3; 173.5; 174.3; 99.2; 111.7; 92.4 | — |
| SECONDARY Change From BL in Peripheral CD16+56+ Cell Count |
-72.2; -60.5; -83.2; 4.0; 4.5; -1.4 | — |
| SECONDARY Percentage of Participants With Total Immunoglobin (Ig), IgA, IgG, and IgM Results Below the LLN |
0.8; 0.9; 1.1; 0.0; 0.0; 0.8 | — |
| SECONDARY Percentage of Participants Who Were Rheumatoid Factor (RF) - Seronegative |
9.7; 9.5; 5.0; 22.9; 21.5; 16.1 | — |
| SECONDARY Anti-Cyclic Citrullinated Peptide (CCP) Antibody Titers at BL in Units Per mL (U/mL) |
205.39; 179.01; 263.61; 184.77; 310.94 | — |
| SECONDARY Change From BL in Anti-CCP Antibody Titers in U/mL |
-42.97; -46.84; -70.39; -33.80; -18.67; -68.23 | — |
| SECONDARY Percentage of Participants With Complement Component 3 (C3) Protein Level ≤ LLN |
3.1; 0.9; 1.2; 3.3; 2.8; 5.7 | — |
| SECONDARY Change From BL in Complement C3 Protein Level in g/L |
-0.0469; -0.0563; -0.0802; -0.0423; -0.0143; -0.0773 | — |
| SECONDARY Change From BL in Activated Complement Component 3a (C3a) Protein Level in g/L |
-326.9; -92.8; 1319.9; -1176.8; -17.1; 1054.1 | — |
| SECONDARY Percentage of Participants With Complement Component 4 (C4) Protein Level ≤ LLN |
2.4; 0.0; 1.2; 4.9; 0.9; 2.3 | — |
| SECONDARY Change From BL in Complement C4 Protein Level in g/L |
-0.0187; -0.0170; -0.0220; -0.0139; -0.0089; -0.0230 | — |
| SECONDARY Change From BL in Activated Complement Component 4a (C4a) Protein Level in g/L |
-1424.3; -480.1; -3749.1; -971.3; 3004.9; 3.5 | — |
| SECONDARY Percentage of Participants With Positive Human Anti-Chimeric Antibody (HACA) Titers |
0.0; 0.9; 0.0; 0.0; 0.0; 5.1 | — |
| SECONDARY Percentage of Participants With a Change From BL by Category in Anti-Nuclear Antibodies (ANA) Titers |
7.1; 1.9; 7.5; 0.0; 4.2; 14.2 | — |
| SECONDARY Percentage of Participants With Positive Recall Antigen Antibody Titers |
94.4; 98.2; 89.8; 100.0; 92.0; 93.9 | — |
Eligibility Criteria
Inclusion Criteria
- adult patients >=18 years of age;
- RA for >=6 months;
- receiving outpatient treatment;
- inadequate response to methotrexate, having received and tolerated it for >=12 weeks, with a stable dose for >=4 weeks.
Exclusion Criteria
- rheumatic autoimmune disease other than RA, or significant systemic involvement secondary to RA;
- inflammatory joint disease other than RA, or other systemic autoimmune disorder;
- diagnosis of juvenile arthritis, or RA before the age of 16;
- previous treatment with >1 biologic agent, any cell-depleting therapies, or concurrent treatment with any biologic agent or DMARD other than methotrexate.
Data sourced from ClinicalTrials.gov (NCT00422383). 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.