A Study of the Effect of Tocilizumab on Markers of Atherogenic Risk in Patients With Moderate to Severe Rheumatoid Arthritis

Rheumatoid Arthritis Clinical Trial

Official title:

A Mechanism of Action Study to Evaluate the Effects of IL-6 Receptor Blockade With Tocilizumab (TCZ) on Lipids, Arterial Stiffness, and Markers of Atherogenic Risk in Patients With Moderate to Severe Active Rheumatoid Arthritis (RA).

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00535782
• Other study ID #: WA19923
• Secondary ID: 2007-001114-17
• Status: Completed
• Phase: Phase 3
• First received: September 24, 2007
• Last updated: November 8, 2012
• Start date: October 2007
• Est. completion date: January 2011

Study information

• Verified date: November 2012
• 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 2 arm study will investigate the effects of tocilizumab on lipids, arterial stiffness, and markers of atherogenic risk in patients with moderate to severe active rheumatoid arthritis. In Part 1 of the study, patients will be randomized to receive either tocilizumab 8mg/kg intravenously or placebo every 4 weeks, in combination with methotrexate 7.5-25 mg weekly. In Part 2, all patients will receive open-label treatment with tocilizumab plus methotrexate.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 132
• Est. completion date: January 2011
• Est. primary completion date: September 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• adult patients, 18-75 years of age

• rheumatoid arthritis (RA) of >6 months duration

• able to receive outpatient treatment

• on methotrexate for at least 12 weeks before entering study, at a stable dose of 7.5-25 mg/week for the last 8 weeks

• oral corticosteroids and non-steroidal anti-inflammatory drugs (NSAIDS) permitted, if at a stable dose for 4 weeks before study start

Exclusion Criteria

• major surgery (including joint surgery) within 8 weeks prior to screening, or planned surgery within 6 months after entering study

• history of, or current inflammatory joint disease or rheumatic autoimmune disease other than RA

• inadequate response to anti-tumor necrosis factor (TNF) agent during the 6 months prior to baseline, or inadequate response to >2 anti-TNF agents

• initiation of treatment with lipid lowering agents within 12 weeks prior to baseline

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Drug:
• Tocilizumab
Administered by intravenous infusion, 8 mg/kg every 4 weeks.
• Placebo
Placebo to tocilizumab administered by intravenous infusion every 4 weeks.
• Methotrexate
Administered orally or parenterally, 7.5-25 mg weekly.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Canada,  Puerto Rico,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in Small Low Density Lipoprotein (sLDL) Particle Numbers	Small LDL particles are associated with an increased risk of cardiovascular disease: more of these small particles lead to a greater risk. The concentration of fasting small LDL particles was determined using the Nuclear Magnetic Resonance (NMR) methodology.	Baseline and Week 12	No
Primary	Change From Baseline to Week 12 in Aortic Pulse Wave Velocity (PWV)	Aortic (central) arterial stiffness was assessed with Pulse Wave Analysis (PWA) of the radial artery and carotid-femoral PWV using applanation tonometry after the patient had rested in a supine position for at least 10 minutes.	Baseline and Week 12	No
Secondary	Change From Baseline to Week 24 in Small Low Density Lipoprotein (sLDL) Particle Numbers	Small LDL particles are associated with an increased risk of cardiovascular disease: more of these small particles lead to a greater risk. The concentration of fasting small LDL particles was determined using the Nuclear Magnetic Resonance (NMR) methodology.	Baseline and Week 24	No
Secondary	Change From Baseline to Week 24 in Aortic Pulse Wave Velocity (PWV)	Aortic (central) arterial stiffness was assessed with Pulse Wave Analysis (PWA) of the radial artery and carotid-femoral PWV using applanation tonometry after the patient had rested in a supine position for at least 10 minutes.	Baseline and Week 24	No
Secondary	Number of Participants Experiencing Adverse Events (AEs)	A severe AE is an event in which the intensity of the event results in an inability to work or perform normal daily activity.; A Serious AE is fatal, life-threatening, requires in-patient hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant or requires intervention to prevent one of the above outcomes.; AEs of special interest include infection, gastrointestinal, infusion reaction (occurring during or within 24 hours of infusion), hepatic disorder, myocardial infarction and stroke.	Up to Week 24	No