Phase 3
N=1,196
A Study to Assess the Effect of Tocilizumab + Methotrexate on Prevention of Structural Joint Damage in Patients With Moderate to Severe Active Rheumatoid Arthritis (RA)
Rheumatoid Arthritis
Bottom Line
View on ClinicalTrials.gov: NCT00106535 ↗Enrolled (actual)
1,196
Serious AEs
17.2%
Results posted
Jun 2011
Primary outcome: Primary: Percentage of Participants With American College of Rheumatology-ACR20 Response — 27.0; 50.6; 56.3 Percentage of participants — p=<0.0001
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- tocilizumab [RoActemra/Actemra] (Drug); Placebo (Drug); Methotrexate (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Hoffmann-La Roche
- Primary completion
- May 2007
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Participants With American College of Rheumatology-ACR20 Response |
27.0; 50.6; 56.3 | <0.0001 sig |
| PRIMARY Change From Baseline in Modified Total Sharp-Genant Score at Week 52 |
1.13; 0.34; 0.29 | <0.0001 sig |
| PRIMARY Change in Physical Function as Measured by the Area Under the Curve (AUC) for the Change From Baseline in the Health Assessment Questionnaire (HAQ) Disability Index at Week 52 |
-58.11; -128.37; -144.06 | <0.0001 sig |
| PRIMARY Change From Baseline in the Modified Total Sharp-Genant Score at Week 104 |
1.96; 0.58; 0.37 | — |
| PRIMARY Change in Physical Function as Measured by the Area Under the Curve for the Change From Baseline in the Health Assessment Questionnaire- Disability Index (HAQ-DI) at Week 104 |
-139.40; -287.50; -320.80 | <0.0001 sig |
| SECONDARY Percentage of Participants With ACR50 Response |
9.7; 25.1; 32.2 | <0.0001 sig |
| SECONDARY Percentage of Participants With ACR70 Response |
2.0; 11.0; 12.6 | <0.0001 sig |
| SECONDARY Swollen Joint Count (66 Joint Count): Mean Change From Baseline at Week 24 |
16.6; 17.0; 17.3; -2.9; -7.9; -9.0 | — |
| SECONDARY Tender Joint Count (68 Joint Count): Mean Change From Baseline at Week 24 |
27.9; 27.9; 29.3; -4.8; -12.2; -14.2 | — |
| SECONDARY Patient's Global Visual Analog Scale (VAS): Mean Change From Baseline at Week 24 |
63.1; 61.0; 62.7; -17.5; -25.2; -25.2 | — |
| SECONDARY Physician's Global VAS: Mean Change From Baseline at Week 24 |
63.1; 62.3; 62.7; -29.0; -36.1; -39.8 | — |
| SECONDARY Patient's Pain VAS: Mean Change From Baseline at Week 24 |
55.3; 53.3; 55.7; -12.5; -19.5; -21.8 | — |
| SECONDARY C-Reactive Protein (CRP): Mean Change From Baseline at Week 24 |
2.235; 2.076; 2.337; -0.3560; -0.9558; -2.0699 | — |
| SECONDARY Erythrocyte Sedimentation Rate: Mean Change From Baseline at Week 24 |
46.5; 45.9; 46.4; -9.5; -21.8; -36.8 | — |
| SECONDARY Health Assessment Questionnaire Disability Index (HAQ-DI): Mean Change From Baseline at Week 24 |
1.5; 1.5; 1.5; -0.32; -0.45; -0.51 | — |
| SECONDARY Percentage of Participants With American College of Rheumatology (ACR20) Response at Week 52 |
24.7; 47.9; 55.8 | — |
| SECONDARY Percentage of Participants With ACR20 Response at Week 104 |
29.3; 49.1; 54.5 | — |
| SECONDARY Percentage of Participants With ACR50 Response at Week 52 |
10.2; 30.3; 36.4 | — |
| SECONDARY Percentage of Participants With ACR50 Response at Week 104 |
19.8; 37.6; 38.9 | — |
| SECONDARY Percentage of Participants With ACR70 Response at Week 52 |
3.8; 16.5; 20.1 | — |
| SECONDARY Percentage of Participants With ACR70 Response at Week 104 |
12.2; 24.3; 22.4 | — |
| SECONDARY Percentage of Participants With ACR70 Response Maintained for 6 Consecutive Months |
5.6; 11.5; 14.3 | — |
| SECONDARY Change From Baseline in Swollen Joint Count at Week 52 |
-2.5; -8.0; -10.2 | — |
| SECONDARY Change From Baseline in Tender Joint Count at Week 52 |
-4.1; -12.3; -15.6 | — |
| SECONDARY Change From Baseline in Patient's Global Assessment of Disease Activity at Week 52 |
-21.1; -27.2; -29.8 | — |
| SECONDARY Change From Baseline in Physicians Global Assessment of Disease Activity at Week 52 |
-35.2; -42.2; -45.4 | — |
| SECONDARY Change From Baseline in the Patient's Pain VAS at Week 52 |
-15.0; -22.9; -26.1 | — |
| SECONDARY Change From Baseline in C-Reactive Protein (CRP) at Week 52 |
-0.3800; -1.0615; -2.2584 | — |
| SECONDARY Change From Baseline in Erythrocyte Sedimentation Rate (ESR) at Week 52 |
-10.9; -25.6; -38.5 | — |
| SECONDARY Change From Baseline in Swollen Joint Count at Week 104 |
-3.5; -9.0; -11.3 | — |
| SECONDARY Change From Baseline in Tender Joint Count at Week 104 |
-5.9; -13.6; -17.7 | — |
| SECONDARY Change From Baseline in Patient's Global Assessment of Disease Activity at Week 104 |
-33.2; -31.6; -33.9 | — |
| SECONDARY Change From Baseline in Physicians Global Assessment of Disease Activity at Week 104 |
-43.9; -49.1; -48.7 | — |
| SECONDARY Change From Baseline in the Patient's Pain VAS at Week 104 |
-25.6; -26.6; -28.9 | — |
| SECONDARY Change From Baseline in C-Reactive Protein (CRP) at Week 104 |
-1.6346; -1.6863; -2.3068 | — |
| SECONDARY Change From Baseline in Erythrocyte Sedimentation Rate (ESR) at Week 104 |
-30.7; -35.4; -36.9 | — |
| SECONDARY Percentage of Participants Who Achieve an Improvement of at Least 0.3 Units From Baseline in the HAQ Disability Index at Week 52 |
52.7; 59.6; 62.7 | — |
| SECONDARY Percentage of Participants Who Achieve an Improvement of at Least 0.3 Units From Baseline in the HAQ Disability Index at Week 104 |
58.3; 63.3; 62.3 | — |
| SECONDARY Area Under Curve (AUC) of the ACRn to Week 24 |
609.11; 2791.49; 3528.89 | — |
| SECONDARY Area Under Curve (AUC) of the ACRn to Week 52 |
5551.25; 10763.54; 12644.01 | <0.0001 sig |
| SECONDARY Area Under Curve (AUC) of the ACRn Score at Week 104 |
21094.97; 27141.08; 30876.59 | — |
| SECONDARY Change From Baseline in Disease Activity Score (DAS28) at Week 24 |
-1.49; -2.45; -3.28 | — |
| SECONDARY Change From Baseline in Disease Activity Score (DAS28) at Week 52 |
-1.88; -2.97; -3.80 | — |
| SECONDARY Change From Baseline in Disease Activity Score (DAS28) at Week 104 |
-3.70; -3.82; -4.14 | — |
| SECONDARY Percentage of Participants With DAS28 Good or Moderate EULAR Response at Week 24 |
5.9; 24.6; 40.7; 28.8; 39.6; 33.7 | — |
| SECONDARY Percentage of Participants With DAS28 Good or Moderate EULAR Response at Week 52 |
7.1; 27.6; 44.0; 22.1; 30.3; 24.1 | — |
| SECONDARY Percentage of Participants With DAS28 Good or Moderate EULAR Response at Week 104 |
23.4; 39.6; 45.7; 9.7; 15.8; 13.1 | — |
| SECONDARY Percentage of Participants With DAS28 Remission at Week 24 |
3.8; 17.8; 33.3 | — |
| SECONDARY Percentage of Participants With DAS28 Remission at Week 52 |
7.7; 30.5; 48.0 | — |
| SECONDARY Percentage of Participants With DAS28 Remission at Week 104 |
52.9; 55.4; 64.7 | — |
| SECONDARY Area Under Curve (AUC) of Disease Activity Score (DAS28) at Week 24 |
895.85; 767.02; 670.45 | — |
| SECONDARY Area Under Curve (AUC) of Disease Activity Score (DAS28) at Week 52 |
1755.25; 1423.12; 1235.80 | — |
| SECONDARY Area Under Curve (AUC) of Disease Activity Score (DAS28) at Week 104 |
2793.01; 2426.11; 2094.71 | — |
| SECONDARY Change From Baseline in Modified Total Sharp-Genant Score at Week 24 |
0.51; 0.22; 0.19 | — |
| SECONDARY Change From Baseline in Modified Total Sharp-Genant Score at Week 80 |
1.60; 0.46; 0.31 | — |
| SECONDARY Change From Baseline in Erosion Score at Week 24 |
0.36; 0.15; 0.11 | 0.0023 sig |
| SECONDARY Change From Baseline in Erosion Score at Week 52 |
0.71; 0.21; 0.17 | 0.0001 sig |
| SECONDARY Change From Baseline in Erosion Score at Week 80 |
1.01; 0.27; 0.18 | — |
| SECONDARY Change From Baseline in Erosion Score at Week 104 |
1.24; 0.34; 0.22 | — |
| SECONDARY Change From Baseline in Joint Space Narrowing Score at Week 24 |
0.15; 0.07; 0.08 | — |
| SECONDARY Change From Baseline in Joint Space Narrowing Score at Week 52 |
0.42; 0.13; 0.12 | — |
| SECONDARY Change From Baseline in Joint Space Narrowing Score at Week 80 |
0.59; 0.19; 0.13 | — |
| SECONDARY Change From Baseline in Joint Space Narrowing Score at Week 104 |
0.72; 0.24; 0.15 | — |
| SECONDARY Percentage of Participants With no Progression of Erosion at Week 24 |
73.9; 83.8; 88.3 | — |
| SECONDARY Percentage of Participants With no Progression of Erosion at Week 52 |
70.0; 82.6; 86.8 | — |
| SECONDARY Percentage of Participants With no Progression of Erosion at Week 104 |
71.1; 78.4; 85.6 | — |
| SECONDARY Percentage of Participants With no Progression of Joint Space Narrowing at Week 24 |
88.3; 91.4; 91.9 | — |
| SECONDARY Percentage of Participants With no Progression of Joint Space Narrowing at Week 52 |
84.5; 90.6; 90.5 | — |
| SECONDARY Percentage of Participants With no Progression of Joint Space Narrowing at Week 104 |
80.3; 86.0; 91.2 | — |
| SECONDARY Change From Baseline in HAQ Disability Index (HAQ-DI) at Week 52 |
-0.39; -0.52; -0.58 | — |
| SECONDARY Change From Baseline in HAQ Disability Index at Week 104 |
-0.50; -0.58; -0.61 | — |
| SECONDARY Change From Baseline in Quality Life Short Form-36 (SF-36) Score at Week 24 |
5.54; 8.15; 8.46; 3.27; 4.63; 5.17 | — |
| SECONDARY Change From Baseline in SF-36 Score at Week 52 |
5.6; 9.2; 10.0; 3.7; 5.6; 5.5 | — |
| SECONDARY Change From Baseline in SF-36 Score at Week 104 |
8.7; 10.1; 9.8; 5.2; 5.7; 6.2 | — |
| SECONDARY Change From Baseline in Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-F) Score at Week 24 |
5.32; 7.14; 6.91 | — |
| SECONDARY Change From Baseline in FACIT-F Score at Week 52 |
5.57; 8.14; 8.27 | — |
| SECONDARY Change From Baseline in FACIT-F Score at Week 104 |
6.62; 7.85; 8.63 | — |
| SECONDARY Change From Baseline in Rheumatoid Factor (RF) at Week 24 in Those Patients With Positive RF |
-44.7; -79.3; -75.6 | — |
| SECONDARY Change From Baseline in Rheumatoid Factor (RF) at Week 52 in Those Patients With Positive RF |
-21.5; 8.6; -71.6 | — |
| SECONDARY Change From Baseline in Rheumatoid Factor (RF) at Week 104 in Those Patients With Positive RF |
-29.0; -25.1; -39.2 | — |
| SECONDARY Time to Onset of ACR20 by Treatment Group |
116.0; 57.0; 57.0 | — |
| SECONDARY Time to Onset of ACR50 by Treatment Group |
NA; 170.0; 141.0 | — |
| SECONDARY Time to Onset of ACR70 by Treatment Group |
NA; NA; NA | — |
| SECONDARY Percentage of Participants Who Withdraw Due to Lack of Sufficient Therapeutic Response |
3.1; 0.3; 0.5 | — |
| SECONDARY Percentage of Participants in Each Treatment Group Who Receive Escape Therapy |
50; 24; 15; 8; 2; 3 | — |
| SECONDARY Percentage of Participants Who Achieved Remission According to the ACR Remission Criteria by Week 24 |
0.0; 0.3; 0.0 | — |
| SECONDARY Percentage of Participants Who Achieved Remission According to the ACR Remission Criteria by Week 52 |
0.0; 1.8; 1.5 | — |
| SECONDARY Percentage of Participants Who Achieved Remission According to the ACR Remission Criteria by Week 104 |
0.0; 2.0; 2.5 | — |
| SECONDARY Percentage of Participants Who Achieved Complete Clinical Response at Week 52 |
0.0; 0.3; 0.5 | — |
| SECONDARY Percentage of Participants Who Achieved Complete Clinical Response at Week 104 |
0; 0.3; 1.0 | — |
| SECONDARY End of Study: Percentage of Participants With ACR Response at Week 260 |
82.9; 64.9; 42.1; 16.7 | — |
| SECONDARY End of Study: Percentage of Participants With DAS28 Remission at Week 260 |
59.4 | — |
| SECONDARY End of Study: Percentage of Participants With DAS28 Low Disease Activity (LDA) at Week 260 |
73.8 | — |
| SECONDARY End of Study: Percentage of Participants With DAS28 European League Against Rheumatism (EULAR) Good or Moderate Response at Week 260 |
74.1; 24.0 | — |
| SECONDARY End of Study: Change From Baseline in Swollen Joint Count at Week 260 |
-14.2 | — |
| SECONDARY End of Study: Change From Baseline in Tender Joint Count at Week 260 |
-23.6 | — |
| SECONDARY End of Study: Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 260 |
-0.58 | — |
| SECONDARY End of Study: Change From Baseline in the Patient's Global Assessment of Disease Activity Visual Analog Scale (VAS) at Week 260 |
-33.7 | — |
| SECONDARY End of Study: Change From Baseline in the Physician's Global Assessment of Disease Activity VAS at Week 260 |
-48.7 | — |
| SECONDARY End of Study: Change From Baseline in the Patient's Pain VAS at Week 260 |
-28.2 | — |
| SECONDARY End of Study: Percentage of Participants With Clinical Improvement in the FACIT-Fatigue Score at Week 260 |
64.1 | — |
| SECONDARY End of Study: Percentage of Participants With Clinical Relevant Improvement in the SF-36 Score at Week 260 |
43.7; 69.9 | — |
| SECONDARY End of Study: Change From Baseline in Total Sharp-Genant Score at Week 260 |
3.30; 1.54 | — |
| SECONDARY End of Study: Change From Baseline in Erosion Score at Week 260 |
1.95; 0.83 | — |
| SECONDARY End of Study: Change From Baseline in Joint Space Narrowing Score at Week 260 |
1.35; 0.71 | — |
Summary
This 3 arm study will compare the safety and efficacy, with respect to a reduction in signs and symptoms and prevention of joint damage, of tocilizumab versus placebo, both in combination with methotrexate (MTX) in patients with moderate to severe active rheumatoid arthritis. Patients will be randomized to receive tocilizumab 4 mg/kg IV, tocilizumab 8 mg/kg IV or placebo IV, every 4 weeks. All patients will also receive methotrexate, 10-25 mg/week. The anticipated time on study treatment is 1-2 years and the target sample size is 500+ individuals. After completion of the 2 year study participants could participate in the optional 3 year open label extension phase (year 3 to 5).
Eligibility Criteria
Inclusion Criteria
- adult patients at least 18 years of age with moderate to severe active RA for at least 6 months;
- inadequate response to a stable dose of MTX;
- patients of reproductive potential must be using reliable methods of contraception.
Exclusion Criteria
- major surgery (including joint surgery) within 8 weeks before entering study, or planned surgery within 6 months after entering study;
- prior treatment failure with an anti-tumor necrosis factor agent;
- women who are pregnant or breast-feeding.
Data sourced from ClinicalTrials.gov (NCT00106535). 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.