A Study of Tocilizumab in Comparison to Etanercept in Participants With Rheumatoid Arthritis and Cardiovascular Disease Risk Factors

Rheumatoid Arthritis Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01331837
• Other study ID #: WA25204
• Secondary ID: 2010-020065-24
• Status: Completed
• Phase: Phase 4
• First received: April 7, 2011
• Last updated: November 1, 2016
• Start date: August 2011
• Est. completion date: March 2016

Study information

• Verified date: November 2016
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 3080
• Est. completion date: March 2016
• Est. primary completion date: March 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 50 Years and older

Eligibility

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

• Any major episode of infection requiring hospitalization or treatment with IV antibiotics within four weeks of screening or oral antibiotics within two weeks prior to screening visit

• Active tuberculosis (TB) requiring treatment within 3 years prior to baseline

• Latent TB diagnosed during screening that has not been appropriately treated

• Primary or secondary immunodeficiency (history of or currently active)

• Moderate to severe heart failure

• Evidence of active malignant disease, malignancies diagnosed within the previous 10 years (including hematologic malignancies and solid tumors, except basal cell carcinoma of the skin that has been excised and cured), or breast cancer diagnosed within the previous 20 years

• Breast feeding mothers

• History of alcohol, drug or chemical abuse within the 6 months prior to screening

• Participants with lack of peripheral venous access

• Participants with a history of allergic reactions to latex

• Previous treatment with non-tumor necrosis factor (non-TNF)-inhibitor biologic therapy

• Treatment with any investigational agent within 4 weeks of screening visit

• Treatment with any cell depleting therapies within 1 year of baseline

• Treatment with IV gamma globulin, plasmapheresis or Prosorba column within 6 months of baseline visit

• Immunization with a live/attenuated vaccine within 4 weeks prior to baseline visit

• Any previous treatment with alkylating agents, such as cyclophosphamide or chlorambucil, or with total lymphoid irradiation

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Drug:
• Etanercept
Participants will receive 50 mg etanercept subcutaneously weekly until switch to another RA therapy or up to 4.9 years.
• Tocilizumab
Participants will receive 8 mg/kg tocilizumab IV every 4 weeks until switch to another RA therapy or up to 4.9 years.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Argentina,  Austria,  Belgium,  Bosnia and Herzegovina,  Canada,  Chile,  Croatia,  Czech Republic,  Ecuador,  France,  Germany,  Greece,  Hungary,  India,  Israel,  Italy,  Latvia,  Lithuania,  Malaysia,  Mexico,  Netherlands,  Philippines,  Poland,  Romania,  Russian Federation,  Serbia,  South Africa,  Spain,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to First Occurrence of Cardiovascular (CV) Events Adjudication Committee (EAC) (CV-EAC) Adjudicated Event, Defined as a Composite of CV Death, Non-Fatal Myocardial Infarction, and Non-Fatal Stroke		Baseline up to 4.9 years	No
Secondary	Time to First Occurrence of Expanded Composite Endpoint, Defined as a Composite of CV Death, Non-Fatal Myocardial Infarction, Non-Fatal Stroke, Non-Elective Coronary Revascularization Procedures, and Hospitalization for Unstable Angina		Baseline up to 4.9 years	No
Secondary	Percentage of Participants with Adverse Events (AEs) and Serious AEs (SAEs)		Baseline up to 4.9 years	No