Phase 3
Completed N=103
TORPEDO Study: A Study on Rapid Effect of Tocilizumab in Patients With Rheumatoid Arthritis With an Inadequate Response to Disease-Modifying Antirheumatic Drugs (DMARDs) or Anti-TNF
Source: ClinicalTrials.gov NCT00977106 ↗Enrolled (actual)
103
Serious AEs
23.3%
Results posted
Sep 2014
Primary outcomePrimary: Percentage of Participants With Clinically Significant Improvement in Health Assessment Questionnaire - Disability Index (HAQ-DI) at Week 4 — 42.0; 49.1 percentage of participants — p=0.472
Summary
This study will assess the onset and maintenance of effect of tocilizumab on relief in patients with active moderate or severe rheumatoid arthritis who have had an inadequate response to DMARDs or anti-TNF. For the first, double-blind, part of the study patients will be randomized to receive an iv infusion of either 8mg/kg tocilizumab or placebo. After 4 weeks this will be followed by 11 months treatment with tocilizumab 8mg/kg iv infusion every 4 weeks. Methotrexate or DMARD therapy will be continued throughout study treatment. Target sample size is >100.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Participants With Clinically Significant Improvement in Health Assessment Questionnaire - Disability Index (HAQ-DI) at Week 4 |
42.0; 49.1 | 0.472 |
| SECONDARY Patient Global Assessment of Disease Activity During the Double-Blind Treatment Period |
58.8; 64.3; 49.0; 54.2; -11.0; -7.4 | 0.377 |
| SECONDARY Patient Global Assessment of Disease Activity During the Open Treatment Period |
51.2; 59.4; 36.0; 32.7; -16.2; -26.7 | — |
| SECONDARY Physician Global Assessment of Disease Activity During the Double-Blind Treatment Period |
60.8; 58.4; 49.2; 44.6; -11.6; -14.3 | 0.502 |
| SECONDARY Physician Global Assessment of Disease Activity During the Open Treatment Period |
49.3; 59.6; 32.9; 28.3; -16.5; -30.8 | — |
| SECONDARY Patient Global Assessment of Pain During the Double-Blind Treatment Period |
60.2; 54.6; 49.1; 46.4; -11.1; -7.3 | 0.434 |
| SECONDARY Patient Global Assessment of Pain During the Open Treatment Period |
48.9; 55.1; 29.6; 32.8; -20.3; -22.2 | — |
| SECONDARY Synovitis Score During the Double-Blind Treatment Period Assessed Using B-Mode Ultrasound |
26.4; 25.8; 26.4; 25.3; -0.1; -0.6 | 0.692 |
| SECONDARY Synovitis Score During the Double-Blind Treatment Period Assessed Using Power Doppler Ultrasound |
10.1; 10.2; 9.6; 8.9; -0.3; -1.4 | 0.137 |
| SECONDARY Percent Change From Baseline in Synovitis Score During the Open Treatment Period Assessed Using B-Mode Ultrasound |
-15.0; -30.5; -43.7 | — |
| SECONDARY Percent Change From Baseline in Synovitis Score During the Open Treatment Period Assessed Using Power Doppler Ultrasound |
121.0; -23.5; 3.6 | — |
| SECONDARY Erythrocyte Sedimentation Rate During the Double-Blind Treatment Period |
27.5; 28.1; 27.6; 11.9; 26.6; 8.2 | — |
| SECONDARY Percent Change From Baseline in Erythrocyte Sedimentation Rate During the Double-Blind Treatment |
8.7; -51.2; 11.5; -65.9 | — |
| SECONDARY Erythrocyte Sedimentation Rate During the Open Treatment Period |
27.8; 6.8; 5.9; 8.0; 4.6 | — |
| SECONDARY C-Reactive Protein During the Double-Blind Treatment Period |
18.6; 14.2; 20.4; 2.3; 17.5; 3.8 | — |
| SECONDARY Percent Change From Baseline in C-Reactive Protein During the Double-Blind Treatment Period |
19.2; -66.2; 18.3; -47.0 | — |
| SECONDARY C- Reactive Protein During the Open Treatment Period |
15.8; 3.9; 3.2; 3.9; 2.6 | — |
| SECONDARY Serum Amyloid A Component During the Double-Blind Treatment Period |
72.0; 57.9; 89.5; 6.7; 61.2; 8.9 | — |
| SECONDARY Percent Change From Baseline in Serum Amyloid A Component During the Double-Blind Treatment Period |
59.5; -41.2; -5.8; -35.5 | — |
| SECONDARY Serum Amyloid A Component During the Open Treatment Period |
58.6; 40.3; 13.3; 7.3; 5.7 | — |
| SECONDARY Beta 2 Microglobulin Levels During the Open Treatment Period |
2.0; 2.0; 1.9; 2.0; 1.9 | — |
| SECONDARY Beta 2 Microglobulin Levels During the Double-Blind Treatment Period |
2.0; 2.0; 2.0; 2.1; 2.0; 2.0 | — |
| SECONDARY Percent Change From Baseline in Beta 2 Microglobulin Levels During the Double-Blind Treatment Period |
2.2; 4.2; -2.3; -0.8 | — |
| SECONDARY Bone Mineral Density |
1018.0; 1033.4; 887.3; 891.3; 825.0; 821.8 | — |
| SECONDARY Percentage of Participants Treated With Corticosteroids Over the 1-Year Tocilizumab Period |
74; 74; 71; 71; 70; 71 | — |
| SECONDARY S-Sclerostin and P-Dkk1 (Wnt Signaling Inhibitor Dickkopf) Over the 1-Year Tocilizumab Period |
0.51; 0.55; 0.51; 0.54; 847.50; 572.45 | — |
| SECONDARY Serum Procollagen Type II N-Propeptide (s-PIINP), Serum Procollagen Type I N Propeptide (s-PINP), and Serum Carboxy-Terminal Collagen Crosslinks-1 (s-CTX-I) Over the 1-Year Tocilizumab Period |
5.59; 6.07; 5.74; 5.86; 0.35; 0.35 | — |
| SECONDARY Serum Osteogenic Growth Peptide (s-OGP) Over the 1-Year Tocilizumab Period |
3.97; 3.94; 3.90 | — |
| SECONDARY Weekly Methotrexate (MTX) Dose |
17.7; 17.1; 16.9 | — |
| SECONDARY HAQ-DI During the Double-Blind Treatment Period |
1.62; 1.60; 1.44; 1.39; -0.18; -0.22 | — |
| SECONDARY HAQ-DI During the Open Treatment Period |
1.45; 1.62; 1.19; 1.06; -0.29; -0.62 | — |
| SECONDARY Functional Assessment of Chronic Illness in Therapy - Fatigue (FACIT-F) During the Double-Blind Treatment Period |
23.9; 26.0; 27.3; 27.7; 29.2; 28.9 | — |
| SECONDARY Percent Change From Baseline in FACIT-F During the Double-Blind Treatment Period |
24.6; 22.7; 37.7; 41.7 | — |
| SECONDARY FACIT-F During the Open Treatment Period |
27.1; 33.7; 35.4; 34.0; 34.9 | — |
| SECONDARY Hemoglobin Concentration During the Double-Blind Treatment Period |
12.97; 12.74; 12.96; 13.04; -0.01; 0.34 | — |
| SECONDARY Hemoglobin Concentration During the Open Treatment Period |
12.80; 13.14; 13.37; 13.24; 13.27; 13.38 | — |
| SECONDARY Tender Joint Count (TJC) Based on 28-Joint Count During the Double-Blind Treatment Period |
12.0; 13.4; 11.0; 10.6; 10.6; 9.9 | — |
| SECONDARY Percent Change From Baseline in TJC Based on 28-Joint Count During the Double-Blind Treatment Period |
3.4; 16.7; 25.7; 9.3 | — |
| SECONDARY TJC Based on 28-Joint Count During the Open Treatment Period |
12.3; 5.5; 4.0; 3.6; 3.3 | — |
| SECONDARY TJC Based on 40-Joint Count During the Double-Blind Treatment Period |
17.7; 18.3; 16.3; 14.6; 15.0; 14.0 | — |
| SECONDARY Percent Change From Baseline in TJC Based on 40-Joint Count During the Double-Blind Treatment Period |
-2.6; -22.1; -1.5; -23.1 | — |
| SECONDARY TJC Based on 40-Joint Count During the Open Treatment Period |
17.0; 7.9; 5.9; 5.2; 5.0 | — |
| SECONDARY Swollen Joint Count (SJC) Based on 28-Joint Count During the Double-Blind Treatment Period |
8.3; 8.5; 6.9; 7.0; 7.7; 5.8 | — |
| SECONDARY Percent Change From Baseline in SJC Based on 28-Joint Count During the Double-Blind Treatment Period |
-12.0; -10.9; -1.1; -27.3 | — |
| SECONDARY Swollen Joint Count (SJC) Based on 28-Joint Count During the Open Treatment Period |
8.2; 3.8; 3.1; 2.2; 1.7 | — |
| SECONDARY SJC Based on 40-Joint Count During the Double-Blind Treatment Period |
10.1; 10.4; 8.7; 8.0; 9.8; 6.7 | — |
| SECONDARY Percent Change From Baseline in SJC Based on 40-Joint Count During the Double-Blind Treatment Period |
-9.2; -19.2; 7.7; -30.0 | — |
| SECONDARY SJC Based on 40-Joint Count During the Open Treatment Period |
10.2; 4.4; 3.5; 2.5; 2.1 | — |
| SECONDARY Disease Activity Score Based on 28-Joints Count (DAS28) During the Double-Blind Treatment Period |
5.66; 5.64; 5.40; 4.41; -0.43; -1.12 | — |
| SECONDARY DAS28 During the Open Treatment Period |
5.51; 2.98; 2.64; 2.51; 2.22 | — |
| SECONDARY Disease Activity Score Based on 40-Joints Count (DAS40) During the Double-Blind Treatment Period |
6.15; 6.08; 5.88; 4.71; -0.43; -1.25 | — |
| SECONDARY DAS40 During the Open Treatment Period |
5.96; 3.27; 2.89; 2.76; 2.48 | — |
Eligibility Criteria
Inclusion Criteria
- adult patients >/= 18 years of age
- active moderate or severe rheumatoid arthritis of <10 years duration with inadequate response to methotrexate or anti-TNF
- on methotrexate treatment for at least 10 weeks, at least 8 weeks on stable dose
- patients receiving oral corticosteroids and/or NSAIDs should be at stable dose for 4 weeks
Exclusion Criteria
- rheumatic autoimmune disease other than RA, or significant systemic involvement secondary to RA
- functional class IV by ACR classification
- history of inflammatory joint disease other than RA
- previous treatment with cell-depleting therapies, abatacept or rituximab
- active current or history of recurrent infection, or any major episode of infection requiring hospitalization or treatment with iv antibiotics <4 weeks or oral antibiotics <2 weeks prior to screening
Data sourced from ClinicalTrials.gov (NCT00977106). 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.