A Clinical Outcomes Study to Evaluate the Effects of IL-6 Receptor Blockade With Tocilizumab (TCZ) in Comparison With Etanercept (ETA) on the Rate of Cardiovascular Events in Patients With Moderate to Severe Rheumatoid Arthritis (RA)
Overview
- Phase
- Phase 4
- Intervention
- Etanercept
- Conditions
- Rheumatoid Arthritis
- Sponsor
- Hoffmann-La Roche
- Enrollment
- 3080
- Locations
- 426
- Primary Endpoint
- Time to First CV-EAC Adjudicated Event Excluding Undetermined Cause of Death - Sensitivity Analysis
- Status
- Completed
- Last Updated
- 8 years ago
Overview
Brief Summary
This randomized, open-label, parallel-group, multicenter study will evaluate the rate of cardiovascular events with tocilizumab in comparison to etanercept in participants with rheumatoid arthritis (RA). Participants will be randomized to receive intravenous (IV) 8 milligrams per kilogram (mg/kg) tocilizumab every 4 weeks or subcutaneous 50 milligrams (mg) etanercept weekly, with or without non-biologic disease-modifying anti-rheumatic drug (DMARD).
Investigators
Eligibility Criteria
Inclusion Criteria
- •Participants with moderate to severe RA of greater than or equal to (\>=6) months duration
- •Inadequate response to at least one non-biologic DMARD
- •Positive for Rheumatoid Factor (RF) and/or anti-cyclic citrullinated peptide (CCP) antibodies at screening
- •Have C-reactive protein (CRP) greater than (\>) 0.3 milligrams per deciliter (mg/dL) at screening or at the baseline visit
- •Swollen joint count (SJC) \>=8 (66 joint count) and tender joint count (TJC) \>= 8 (68 joint count) during screening or at the baseline visit
- •History of Coronary Heart Disease (CHD) or presence of one or more additional CHD risk factors, including current cigarette smoking, hypertension, low High Density Lipoprotein (HDL) cholesterol, family history of premature CHD, diabetes, presence of extra-articular disease associated with rheumatoid arthritis
- •At the time of randomization, will have discontinued infliximab, adalimumab, golimumab, or certolizumab for \>= 4 weeks
Exclusion Criteria
- •Major surgery (including joint surgery or coronary revascularization) within 8 weeks prior to screening or planned major surgery within 1 year of study start
- •Rheumatic autoimmune disease other than RA
- •History of or current inflammatory joint disease other than RA
- •Current or recent (within past 3 months) evidence of serious uncontrolled concomitant cardiovascular or cerebrovascular disease (myocardial infarction, revascularization, stroke, transient ischemic attack, or acute coronary syndrome)
- •Current or previous (within the past 2 years) evidence of serious uncontrolled concomitant pulmonary (including obstructive pulmonary disease), renal, hepatic, endocrine (including uncontrolled diabetes mellitus) or gastrointestinal disease
- •Uncontrolled disease states, such as asthma or inflammatory bowel disease where flares are commonly treated with oral or parenteral corticosteroids
- •Pre-existing central nervous system demyelinating or seizure disorders
- •History of diverticulitis, diverticulosis requiring treatment or other lower gastrointestinal tract conditions that might predispose to perforations
- •Current liver disease as determined by the investigator; a history of asymptomatic elevations in liver function tests (LFTs) is not considered an exclusion
- •Active current infection or history of recurrent bacterial, viral, fungal, mycobacterial or other infections, including but not limited to tuberculosis and atypical mycobacterial disease, hepatitis B and C, and herpes zoster, but excluding fungal infections of nail beds
Arms & Interventions
Etanercept
Intervention: Etanercept
Tocilizumab
Intervention: Tocilizumab
Outcomes
Primary Outcomes
Time to First CV-EAC Adjudicated Event Excluding Undetermined Cause of Death - Sensitivity Analysis
Time Frame: From baseline up to 4.9 years
Prospective comparison of time to first occurrence of any component of the composite of CV death (excluding events adjudicated as 'Undetermined Cause of Death'), non-fatal myocardial infarction, or non-fatal stroke - Sensitivity Analyses
Percentage of Patients Reporting a Cardiovascular (CV) Events Adjudication Committee (EAC) (CV-EAC) Adjudicated Event
Time Frame: From baseline up to 4.9 years
Percentage of patients reporting any component of the composite of CV death (including events adjudicated as 'Undetermined Cause of Death'), non-fatal myocardial infarction, or non-fatal stroke
Time to First CV-EAC Adjudicated Event - Sensitivity Analysis
Time Frame: From Baseline up to 4.9 years
Prospective comparison of time to first occurrence of any component of the composite of CV death (including events adjudicated as 'Undetermined Cause of Death'), non-fatal myocardial infarction, or non-fatal stroke - Sensitivity Analysis
Time to First CV-EAC Adjudicated Event Before Last Direct Contact Date
Time Frame: From Baseline up to 4.9 years
Prospective comparison of time to first occurrence of any component of the composite of CV death (including events adjudicated as 'Undetermined Cause of Death'), non-fatal myocardial infarction, or non-fatal stroke before last direct contact date (i.e., latest date of visit, IVRS call, or site call).
Percentage of Participants With a CV-EAC Adjudicated Event Before Last Direct Contact Date
Time Frame: From Baseline up to 4.9 years
Percentage of participants with any component of the composite of CV death (including events adjudicated as 'Undetermined Cause of Death'), non-fatal myocardial infarction, or non-fatal stroke before last direct contact date (i.e., latest date of visit, IVRS call, or site call).
Time to First Cardiovascular (CV) Events Adjudication Committee (EAC) (CV-EAC) Adjudicated Event
Time Frame: From baseline up to 4.9 years
Prospective comparison of time to first occurrence of any component of the composite of CV death (including events adjudicated as 'Undetermined Cause of Death'), non-fatal myocardial infarction, or non-fatal stroke.
Percentage of Patients With a CV-EAC Adjudicated Event - Sensitivity Analysis
Time Frame: From Baseline up to 4.9 years
Percentage of patients with any component of the composite of CV death (including events adjudicated as 'Undetermined Cause of Death'), non-fatal myocardial infarction, or non-fatal stroke - Sensitivity Analysis
Percentage of Patients With a CV-EAC Adjudicated Event Excluding Undetermined Cause of Death - Sensitivity Analysis
Time Frame: From baseline up to 4.9 years
Percentage of patients with any component of the composite of CV death (excluding events adjudicated as 'Undetermined Cause of Death'), non-fatal myocardial infarction, or non-fatal stroke - Sensitivity Analyses
Secondary Outcomes
- The Time to First Occurrence of an Expanded CV Composite Endpoint(From baseline up to 4.9 years)
- Percentages of Participants With an Expanded CV Composite Endpoint(From baseline up to 4.9 years)
- Time to First Occurrence of Individual Component of Primary Endpoint: Non-fatal Myocardial Infarction(From baseline up to 4.9 years)
- Percentage of Patients With Individual Component of Primary Endpoint: Non-fatal Myocardial Infarction(From baseline up to 4.9 years)
- Time to First Occurrence of Individual Component of Primary Endpoint: Cardiovascular Death(From baseline up to 4.9 years)
- Percentage of Patients With Individual Component of Primary Endpoint: Cardiovascular Death(From baseline up to 4.9 years)
- Percentage of Patients With Individual Component of Primary Endpoint: Non-fatal Stroke(From baseline up to 4.9 years)
- Time to First Occurrence of Individual Component of Primary Endpoint: Non-fatal Stroke(From baseline up to 4.9 years)
- Time to First Occurrence of Individual Component of Primary Endpoint: All-cause Mortality(From baseline up to 4.9 years)
- Percentage of Patients With Individual Component of Primary Endpoint: All-cause Mortality(From baseline up to 4.9 years)