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

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ClinicalTrials.gov Identifier: NCT00535782
Recruitment Status : Completed
First Posted : September 26, 2007
Results First Posted : November 14, 2012
Last Update Posted : July 26, 2017
Sponsor:
Information provided by (Responsible Party):

Study Description
Brief 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.

Condition or disease Intervention/treatment Phase
Rheumatoid Arthritis Drug: Tocilizumab Drug: Placebo Drug: Methotrexate Phase 3

Study Design

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 132 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, 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).
Actual Study Start Date : October 31, 2007
Primary Completion Date : September 30, 2008
Study Completion Date : January 31, 2011

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
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.


Outcome Measures

Primary Outcome Measures :
  1. Change From Baseline in Small Low Density Lipoprotein (sLDL) Particle Numbers [ Time Frame: Baseline and Week 12 ]
    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.

  2. Change From Baseline to Week 12 in Aortic Pulse Wave Velocity (PWV) [ Time Frame: Baseline and Week 12 ]
    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 :
  1. Change From Baseline to Week 24 in Small Low Density Lipoprotein (sLDL) Particle Numbers [ Time Frame: Baseline and Week 24 ]
    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.

  2. Change From Baseline to Week 24 in Aortic Pulse Wave Velocity (PWV) [ Time Frame: Baseline and Week 24 ]
    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.

  3. Number of Participants Experiencing Adverse Events (AEs) [ Time Frame: Up to Week 24 ]

    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.



Eligibility Criteria

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Senior)
Sexes Eligible for Study:   All
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00535782


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Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT00535782     History of Changes
Other Study ID Numbers: WA19923
2007-001114-17
First Posted: September 26, 2007    Key Record Dates
Results First Posted: November 14, 2012
Last Update Posted: July 26, 2017
Last Verified: June 2017

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
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