Phase 3
Completed N=210
A Study of the Efficacy and Safety of Tocilizumab in Participants With Systemic Sclerosis (SSc)
Source: ClinicalTrials.gov NCT02453256 ↗Enrolled (actual)
210
Serious AEs
12.3%
Results posted
Apr 2019
Primary outcomePrimary: Change in Modified Rodnan Skin Score (mRSS) During Double-blind Period — -4.41; -6.14 Units on a scale — p=0.0983
◆ Published Evidence
Highly cited
652citations · ~109 / year
Tocilizumab in systemic sclerosis: a randomised, double-blind, placebo-controlled, phase 3 trial.
Summary
This study will assess the efficacy and safety of tocilizumab compared with placebo in participants with SSc across approximately 120 planned global study sites. The study will consist of a 48-week, double-blind, placebo-controlled period followed by a 48-week open-label treatment period. Participants will be assigned, in a 1:1 ratio, to double-blind treatment with active tocilizumab or matching placebo. In the open-label period, eligible participants from either arm may receive active tocilizumab.
Linked Publications (5)
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Tocilizumab in systemic sclerosis: a randomised, double-blind, placebo-controlled, phase 3 trial.
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Tocilizumab Prevents Progression of Early Systemic Sclerosis-Associated Interstitial Lung Disease.
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Long-Term Safety and Efficacy of Tocilizumab in Early Systemic Sclerosis-Interstitial Lung Disease: Open-Label Extension of a Phase 3 Randomized Controlled Trial.
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Osteopontin Links Myeloid Activation and Disease Progression in Systemic Sclerosis.
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Prognostic and predictive markers of systemic sclerosis-associated interstitial lung disease in a clinical trial and long-term observational cohort.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change in Modified Rodnan Skin Score (mRSS) During Double-blind Period |
-4.41; -6.14 | 0.0983 |
| SECONDARY Percentage of Participants With Greater Than or Equal to (>/=) 20%, 40%, or 60% Improvement in mRSS During Double-blind Period |
50.0; 72.1; 37.7; 42.3; 22.6; 17.3 | 0.0007 sig |
| SECONDARY Change From Baseline in Percent Predicted FVC (ppFVC) During Double-blind Period |
-3.910; -0.600 | 0.0015 sig |
| SECONDARY Change in Forced Vital Capacity (FVC) During Double-blind Period |
-0.19; -0.02 | 0.0001 sig |
| SECONDARY Change in Health Assessment Questionnaire Disability Index (HAQ-DI) Score During Double-blind Period |
-0.06; -0.11 | 0.4489 |
| SECONDARY Change in Patient Global Assessment Score During Double-blind Period |
-7.66; -10.10 | 0.4339 |
| SECONDARY Change in Physician Global Assessment Score During Double-blind Period |
-19.99; -22.45 | 0.4378 |
| SECONDARY Time to Treatment Failure According to mRSS, FVC, or Protocol-Specified Event During Double-blind Period |
NA; NA | 0.0821 |
| SECONDARY Summary of Adverse Events During Double-blind Period |
77.4; 85.6; 3.8; 2.9; 2.8; 1.0 | — |
| SECONDARY Incidence and Severity of Adverse Events During Double-blind Period |
6; 10; 2; 3; 5; 1 | — |
| SECONDARY Number of Participants With Adverse Events Leading to Death During Double-blind Period |
1; 0; 1; 0; 1; 0 | — |
| SECONDARY Frequency of Serious Systemic Sclerosis (SSC) Related Complications During Double-blind Period |
0; 1; 1; 0; 1; 0 | — |
| SECONDARY Incidence of Haematology and Hepatic Laboratory Parameters During Double-blind Period |
7; 1; 17; 32; 17; 24 | — |
| SECONDARY Percentage of Participants With Change in Digital Ulcer Count During Double-blind Period |
85.4; 87.2; 3.4; 5.3; 1.1; 1.1 | — |
| SECONDARY Percentage of Participants With Positive Anti-Tocilizumab Assay Result at Baseline |
5.9; 2.9 | — |
| SECONDARY Percentage of Participants With Positive Anti-Tocilizumab Assay Post-Baseline up to Week 48 |
0.0; 2.9; 0.0; 1.0; 0.0; 1.0 | — |
| SECONDARY Correlation Between Anti-Tocilizumab Antibody Status and Outcome Measures Pertaining to the Efficacy, Safety, and Pharmacokinetics of Tocilizumab |
NA; NA | — |
| SECONDARY Erythrocyte Sedimentation Rate (ESR), Mean, From Baseline to Week 48 |
34.72; 34.83; 31.38; 14.29; 28.49; 8.46 | — |
| SECONDARY Erythrocyte Sedimentation Rate (ESR), Median, From Baseline to Week 48 |
33.0; 33.50; 30.00; 9.50; 25.00; 5.00 | — |
| SECONDARY Serum Interleukin (IL)-6 Level, Mean, From Baseline to Week 48 |
11.83; 13.88; 13.41; 143.97; 14.21; 111.44 | — |
| SECONDARY Serum Interleukin (IL)-6 Level, Median, From Baseline to Week 48 |
5.21; 4.65; 5.31; 56.50; 5.15; 58.65 | — |
| SECONDARY Serum Interleukin (IL)-6 Level, Mean Change From Baseline to Week 48 |
1.11; 130.60; 2.43; 97.22; 3.07; 57.10 | — |
| SECONDARY Serum Interleukin (IL)-6 Level, Median Change From Baseline to Week 48 |
-0.12; 52.41; 0.83; 52.35; 0.34; 42.35 | — |
| SECONDARY Serum Soluble Interleukin (IL)-6 Receptor Level, Mean, From Baseline to Week 48 |
42.16; 42.22; 46.07; 486.58; 45.71; 546.59 | — |
| SECONDARY Serum Soluble Interleukin (IL)-6 Receptor Level, Median, From Baseline to Week 48 |
37.10; 39.00; 38.10; 482.50; 37.20; 536.00 | — |
| SECONDARY Serum Soluble Interleukin (IL)-6 Receptor Level, Mean Change From Baseline to Week 48 |
3.96; 444.23; 3.31; 501.09; 6.04; 539.21 | — |
| SECONDARY Serum Soluble Interleukin (IL)-6 Receptor Level, Median Change From Baseline to Week 48 |
0.20; 437.80; 0.20; 489.90; 0.25; 542.30 | — |
| SECONDARY Serum C-Reactive Protein (CRP) Level, Mean, From Baseline to Week 48 |
7.43; 9.00; 9.81; 0.85; 9.89; 0.56 | — |
| SECONDARY Serum C-Reactive Protein (CRP) Level, Median, From Baseline to Week 48 |
3.82; 4.05; 3.71; 0.20; 4.15; 0.20 | — |
| SECONDARY Serum Tocilizumab Concentration, Mean, From Baseline to Week 48 |
0.00; 30.92; 41.82; 50.98; 54.34; 53.55 | — |
| SECONDARY Serum Tocilizumab Concentration, Median, From Baseline to Week 48 |
0.00; 28.70; 39.25; 47.40; 52.60; 52.50 | — |
| SECONDARY Correlation Between Low Serum Tocilizumab Exposure and Mean Modified Rodnan Skin Score (mRSS) From Baseline to Week 48 |
20.4; 20.3; 18.6; 17.9; 17.9; 16.2 | — |
| SECONDARY Correlation Between Low Serum Tocilizumab Exposure and Median Modified Rodnan Skin Score (mRSS) From Baseline to Week 48 |
19.0; 20.0; 18.0; 16.0; 17.0; 15.0 | — |
| SECONDARY Correlation Between Medium Serum Tocilizumab Exposure and Mean Modified Rodnan Skin Score (mRSS) From Baseline to Week 48 |
20.4; 19.1; 18.6; 17.2; 17.9; 16.2 | — |
| SECONDARY Correlation Between Medium Serum Tocilizumab Exposure and Median Modified Rodnan Skin Score (mRSS) From Baseline to Week 48 |
19.0; 18.0; 18.0; 17.0; 17.0; 16.0 | — |
| SECONDARY Correlation Between High Serum Tocilizumab Exposure and Mean Modified Rodnan Skin Score (mRSS) From Baseline to Week 48 |
20.4; 19.8; 18.6; 17.9; 17.9; 16.7 | — |
| SECONDARY Correlation Between High Serum Tocilizumab Exposure and Median Modified Rodnan Skin Score (mRSS) From Baseline to Week 48 |
19.0; 19.0; 18.0; 17.5; 17.0; 15.0 | — |
| SECONDARY Change in Mean Modified Rodnan Skin Score (mRSS) at Low, Medium and High Serum Tocilizumab Exposure From Baseline to Week 48 |
-5.3; -8.0; -5.3; -7.5; -5.3; -7.0 | — |
| SECONDARY Change in Median Modified Rodnan Skin Score (mRSS), at Low, Medium and High Serum Tocilizumab Exposure From Baseline to Week 48 |
-5.5; -8.0; -5.5; -7.0; -5.5; -6.0 | — |
| SECONDARY Change in Mean Percent Predicted Forced Vital Capacity (ppFVC), at Low, Medium and High Serum Tocilizumab Exposure From Baseline to Week 48 |
-4.264; 0.144; -4.264; -0.161; -4.264; -0.297 | — |
| SECONDARY Change in Median Percent Predicted Forced Vital Capacity (ppFVC), at Low, Medium and High Serum Tocilizumab Exposure From Baseline to Week 48 |
-3.910; 0.525; -3.910; -1.600; -3.910; 0.000 | — |
| SECONDARY Summary of Adverse Events Up to Week 96 |
77.4; 85.6; 77.5; 71.7; 12.3; 6.7 | — |
| SECONDARY Incidence and Severity of Adverse Events Up to Week 96 |
61; 78; 60; 53; 63; 53 | — |
| SECONDARY Number of Participants With Adverse Events Leading to Death Up to Week 96 |
1; 0; 0; 0; 1; 0 | — |
| SECONDARY Percentage of Participants With Change in Digital Ulcer Count at Week 96 |
0; 0; 91.1; 83.3; 0; 0 | — |
| SECONDARY Percentage of Participants With Positive Anti-Tocilizumab Assay Post-Baseline From Week 48 to 96 |
0.0; 0.0; 0.0 | — |
| SECONDARY Erythrocyte Sedimentation Rate (ESR) Up to Week 96 |
34.72; 34.83; 31.38; 14.29; 28.49; 8.46 | — |
| SECONDARY Serum Interleukin (IL)-6 Level, Mean, From Baseline to Week 96 |
11.85; 13.86; 13.41; 144.75; 14.21; 111.44 | — |
| SECONDARY Serum Soluble Interleukin (IL)-6 Receptor Level, Mean, Up to Week 96 |
42.23; 42.15; 46.07; 487.70; 45.71; 546.59 | — |
| SECONDARY Serum C-Reactive Protein (CRP) Level, Mean, Up to Week 96 |
7.42; 8.99; 10.05; 0.85; 9.89; 0.56 | — |
| SECONDARY Serum Tocilizumab Concentration, Mean, Up to Week 96 |
0.00; 30.76; 41.82; 50.98; 54.34; 53.55 | — |
Eligibility Criteria
Inclusion Criteria
- Diagnosis of SSc according to American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) criteria, meeting criteria for active disease and with total disease duration of less than or equal to (</=) 60 months
- mRSS of 10-35 units, inclusive
- Agreement to remain abstinent or use an effective contraceptive method among males and females with childbearing potential
Exclusion Criteria
- Pregnant or lactating females
- Major surgery within 8 weeks prior to screening
- Scleroderma limited to the face or areas distal to the elbows or knees
- Rheumatic autoimmune disease other than SSc
- Immunization with a live or attenuated vaccine within 4 weeks prior to Baseline
- Known hypersensitivity to human, humanized, or murine monoclonal antibodies
- Moderately severe nervous system, renal, endocrine, pulmonary, cardiovascular, or gastrointestinal (GI) disease not related to SSc, including diverticulitis or ulcerative lower GI disorders, or myocardial infarction (MI) within 6 months prior to screening
- Active or significant history of infection, including treatment with intravenous (IV) antibiotics within 4 weeks or oral antibiotics within 2 weeks prior to screening
- Significant history of tuberculosis (TB)
- Primary or secondary immunodeficiency
- Malignant disease, with the exception of excised/cured local basal or squamous cell carcinoma of the skin or carcinoma in situ of the uterine cervix
- History of drug or alcohol abuse
Data sourced from ClinicalTrials.gov (NCT02453256) and the linked publication. 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.