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

Purpose

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.

Condition	Intervention	Phase
Rheumatoid Arthritis	Drug: Tocilizumab Drug: Placebo Drug: Methotrexate	Phase 3

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

Resource links provided by NLM:

MedlinePlus related topics: Rheumatoid Arthritis

Drug Information available for: Methotrexate Methotrexate sodium Tocilizumab

U.S. FDA Resources

Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:

Change From Baseline in Small Low Density Lipoprotein (sLDL) Particle Numbers [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
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.
Change From Baseline to Week 12 in Aortic Pulse Wave Velocity (PWV) [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
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.

Secondary Outcome Measures:

Change From Baseline to Week 24 in Small Low Density Lipoprotein (sLDL) Particle Numbers [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]
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.
Change From Baseline to Week 24 in Aortic Pulse Wave Velocity (PWV) [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]
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.
Number of Participants Experiencing Adverse Events (AEs) [ Time Frame: Up to Week 24 ] [ Designated as safety issue: No ]
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.

Enrollment:	132
Study Start Date:	October 2007
Study Completion Date:	January 2011
Primary Completion Date:	September 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: TCZ + MTX Participants received 8 mg/kg tocilizumab (TCZ) by intravenous infusion (IV) every 4 weeks plus methotrexate (MTX) 7.5-25 mg (oral or parenteral) weekly for the first 24 weeks. From Week 24 to Week 104, participants received open-label TCZ 8 mg/kg every 4 weeks plus 7.5-25 mg MTX weekly.	Drug: Tocilizumab Administered by intravenous infusion, 8 mg/kg every 4 weeks. Other Names: RoActemra Actemra Drug: Methotrexate Administered orally or parenterally, 7.5-25 mg weekly.
Placebo Comparator: Placebo + MTX Participants received placebo intravenous infusion (IV) every 4 weeks plus methotrexate (MTX) 7.5-25 mg (oral or parenteral) weekly for the first 24 weeks. From Week 24 to 104, participants received open-label tocilizumab (TCZ) 8 mg/kg every 4 weeks plus 7.5-25 mg MTX.	Drug: Tocilizumab Administered by intravenous infusion, 8 mg/kg every 4 weeks. Other Names: RoActemra Actemra Drug: Placebo Placebo to tocilizumab administered by intravenous infusion every 4 weeks. Drug: Methotrexate Administered orally or parenterally, 7.5-25 mg weekly.

Eligibility

Ages Eligible for Study:	18 Years to 75 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00535782

Show 39 Study Locations

Sponsors and Collaborators

Hoffmann-La Roche

Investigators

Study Director:

Clinical Trials

Hoffmann-La Roche

More Information

No publications provided

Responsible Party:	Hoffmann-La Roche
ClinicalTrials.gov Identifier:	NCT00535782 History of Changes
Other Study ID Numbers:	WA19923, 2007-001114-17
Study First Received:	September 24, 2007
Results First Received:	August 8, 2012
Last Updated:	November 8, 2012
Health Authority:	United States: Food and Drug Administration

Additional relevant MeSH terms:

Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Methotrexate
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs

Pharmacologic Actions
Therapeutic Uses
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on May 22, 2013