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

June 28, 2017 updated by: Hoffmann-La Roche

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).

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
132

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
      • Quebec, Canada, G1W 4R4
        • Centre Re Recherche Saint-Louis
    • Alberta
      • Edmonton, Alberta, Canada, T6G 2S2
        • The Governors of the Uni of Alberta; Heritage Medical Research Centre
    • British Columbia
      • Vancouver, British Columbia, Canada, V5Z 3Y1
        • Laurel Medical Clinic
    • Manitoba
      • Winnipeg, Manitoba, Canada, R3A 1M3
        • Manitoba Clinic
    • Newfoundland and Labrador
      • St John's, Newfoundland and Labrador, Canada, A1A 5E8
        • Nexus Clinical Research Centre
    • Ontario
      • Hamilton, Ontario, Canada, L8N 1Y2
        • Dr. William G. Bensen Medicine Professional Corporation
      • Mississauga, Ontario, Canada, L5M 2V8
        • Credit Valley, Rheumatology
      • Ottawa, Ontario, Canada, K1H 1A2
        • Rheumatology Research Associates
      • Toronto, Ontario, Canada, M4K 1N2
        • Private Practice
    • Quebec
      • Sherbrooke, Quebec, Canada, J1H 5N4
        • CHUS Hopital Fleurimont
  • Puerto Rico
      • Ponce, Puerto Rico, 00716
        • Ponce School of Medicine; Caimed Center
  • United Kingdom
      • Glasgow, United Kingdom, G4 0SF
        • Glasgow Royal Infirmary; Centre For Rheumatic Diseases
      • Manchester, United Kingdom, M41 5SL
        • Trafford General Hospital; Rheumatology
      • Newcastle Upon Tyne, United Kingdom, NE1 4LP
        • Royal Victoria Infirmary; Clinical Research Facility
  • United States
    • Alabama
      • Anniston, Alabama, United States, 36207
        • Pinnacle Research Group; Llc, Central
      • Huntsville, Alabama, United States, 35801
        • Rheumatology Associates of North Alabama
    • Arizona
      • Scottsdale, Arizona, United States, 85258
        • Advanced Arthritis Care & Research
      • Tucson, Arizona, United States, 85704
        • Catalina Pointe Clinical Research, Inc.
    • California
      • Los Angeles, California, United States, 90045
        • Pacific Arthritis Care Center
    • Florida
      • Aventura, Florida, United States, 33180
        • Arthritis & Rheumatism; Disease Specialities
      • Jupiter, Florida, United States, 33458
        • Science and Research Institute, Inc.
      • Palm Harbor, Florida, United States, 34684
        • Arthritis Center Palm Harbor
      • Palm Harbor, Florida, United States, 34684
        • Arthritis Rsrch of Florida, Inc.
      • Sarasota, Florida, United States, 34239
        • Sarasota Arthritis Center; Research Dept
      • Tampa, Florida, United States, 33614
        • Burnette & Silverfield, MDS
    • Georgia
      • Atlanta, Georgia, United States, 30342
        • Arthritis & Rheumatology of Georgia
    • Illinois
      • Vernon Hills, Illinois, United States, 60061
        • Deerbrook Medical Associates
    • Maryland
      • Baltimore, Maryland, United States, 21224
        • Johns Hopkins Uni
    • Michigan
      • Kalamazoo, Michigan, United States, 49048
        • Borgess Research Institute
    • Mississippi
      • Flowood, Mississippi, United States, 39232
        • Jackson Arthritis Clinic
    • Missouri
      • Saint Louis, Missouri, United States, 63131
        • Physicians Group, LC DBA Rheumatology & Internal Medicine Associates
    • New Jersey
      • Clifton, New Jersey, United States, 07012
        • NJP Clinical Research
    • North Carolina
      • Asheville, North Carolina, United States, 28803
        • Asheville Arthritis & Osteoporosis Center, PA
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73103
        • Health Research of Oklahoma, Llc
    • Pennsylvania
      • Allentown, Pennsylvania, United States, 18103
        • Lehigh Valley Hospital; Dept of Medicine
      • Duncansville, Pennsylvania, United States, 16635
        • Altoona Center For Clinical Research
      • Wyomissing, Pennsylvania, United States, 19610
        • Clinical Research Center of Reading
    • Texas
      • Houston, Texas, United States, 77074
        • Houston Inst. For Clinical Research
      • Sugar Land, Texas, United States, 77479
        • Texas Research Center
    • Washington
      • Olympia, Washington, United States, 98502
        • South Puget Sound Clinical Research

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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: Methotrexate
Administered orally or parenterally, 7.5-25 mg weekly.
Drug: Placebo
Placebo to tocilizumab administered by intravenous infusion every 4 weeks.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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.
Baseline and Week 12
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.
Baseline and Week 12

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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.
Baseline and Week 24
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.
Baseline and Week 24
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.
Up to Week 24

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Hoffmann-La Roche

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 31, 2007

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 30, 2008

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 31, 2011

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 24, 2007

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 24, 2007

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 26, 2007

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
July 26, 2017

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 28, 2017

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2017

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • WA19923
  • 2007-001114-17

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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