Rheumatoid ArthritisPhase 3NCT00535782

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

A Phase 3 study testing Tocilizumab and Methotrexate in people with Rheumatoid Arthritis, run by Hoffmann-La Roche at 40 sites in 4 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 to 75 years
Conditions the study is for: Rheumatoid Arthritis
What is being tested?: Tocilizumab and Methotrexate
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 132 participants
Where: 40 sitesin 4 countries
Study dates: 31 Oct 2007to 31 Jan 2011
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 75 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Who cannot join

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

Trial locations and contacts

40 sites in 4 countries.

Country

City, postcode or hospital

40 sites in 4 countries

United States26 sites

Lehigh Valley Hospital; Dept of Medicine
Allentown, Pennsylvania, 18103
Pinnacle Research Group; Llc, Central
Anniston, Alabama, 36207
Asheville Arthritis & Osteoporosis Center, PA
Asheville, North Carolina, 28803
Arthritis & Rheumatology of Georgia
Atlanta, Georgia, 30342
Arthritis & Rheumatism; Disease Specialities
Aventura, Florida, 33180
Johns Hopkins Uni
Baltimore, Maryland, 21224
NJP Clinical Research
Clifton, New Jersey, 07012
Altoona Center For Clinical Research
Duncansville, Pennsylvania, 16635
Jackson Arthritis Clinic
Flowood, Mississippi, 39232
Houston Inst. For Clinical Research
Houston, Texas, 77074
Rheumatology Associates of North Alabama
Huntsville, Alabama, 35801
Science and Research Institute, Inc.
Jupiter, Florida, 33458
Borgess Research Institute
Kalamazoo, Michigan, 49048
Pacific Arthritis Care Center
Los Angeles, California, 90045
Health Research of Oklahoma, Llc
Oklahoma City, Oklahoma, 73103
South Puget Sound Clinical Research
Olympia, Washington, 98502
Arthritis Center Palm Harbor
Palm Harbor, Florida, 34684
Arthritis Rsrch of Florida, Inc.
Palm Harbor, Florida, 34684
Sarasota Arthritis Center; Research Dept
Sarasota, Florida, 34239
Advanced Arthritis Care & Research
Scottsdale, Arizona, 85258
Physicians Group, LC DBA Rheumatology & Internal Medicine Associates
St Louis, Missouri, 63131
Texas Research Center
Sugar Land, Texas, 77479
Burnette & Silverfield, MDS
Tampa, Florida, 33614
Catalina Pointe Clinical Research, Inc.
Tucson, Arizona, 85704
Deerbrook Medical Associates
Vernon Hills, Illinois, 60061
Clinical Research Center of Reading
Wyomissing, Pennsylvania, 19610

Other trials in United States

Canada10 sites

The Governors of the Uni of Alberta; Heritage Medical Research Centre
Edmonton, Alberta, T6G 2S2
Dr. William G. Bensen Medicine Professional Corporation
Hamilton, Ontario, L8N 1Y2
Credit Valley, Rheumatology
Mississauga, Ontario, L5M 2V8
Rheumatology Research Associates
Ottawa, Ontario, K1H 1A2
Centre Re Recherche Saint-Louis
Québec, G1W 4R4
Chus Hopital Fleurimont
Sherbrooke, Quebec, J1H 5N4
Nexus Clinical Research Centre
St. John's, Newfoundland and Labrador, A1A 5E8
Private Practice
Toronto, Ontario, M4K 1N2
Laurel Medical Clinic
Vancouver, British Columbia, V5Z 3Y1
Manitoba Clinic
Winnipeg, Manitoba, R3A 1M3

Other trials in Canada

United Kingdom3 sites

Glasgow Royal Infirmary; Centre For Rheumatic Diseases
Glasgow, G4 0SF
Trafford General Hospital; Rheumatology
Manchester, M41 5SL
Royal Victoria Infirmary; Clinical Research Facility
Newcastle upon Tyne, NE1 4LP

Other trials in United Kingdom

Puerto Rico1 site

Ponce School of Medicine; Caimed Center
Ponce, 00716

Other trials in Puerto Rico

About this study

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).

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.

Conditions: Rheumatoid Arthritis
Being tested: Tocilizumab, Placebo, Methotrexate
Medical subject headings: Arthritis, Rheumatoid

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

TocilizumabDrug
Also called RoActemra, Actemra
Administered by intravenous infusion, 8 mg/kg every 4 weeks.
PlaceboDrug
Placebo to tocilizumab administered by intravenous infusion every 4 weeks.
MethotrexateDrug
Administered orally or parenterally, 7.5-25 mg weekly.

Study groups in NCT00535782
Study group	Role	What they receive
TCZ + MTX	Experimental	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. Receives: Drug: Tocilizumab; Drug: Methotrexate
Placebo + MTX	Placebo comparator	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. Receives: Drug: Tocilizumab; Drug: Placebo; Drug: Methotrexate

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: Baseline and Week 12
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.
Measured: Baseline and Week 12

Secondary outcomes (3)

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.
Measured: Baseline and Week 24
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.
Measured: Baseline and Week 24
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.
Measured: Up to Week 24

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

31 Oct 200731 Jan 2011

First posted26 Sep 2007 (estimated)
Study start31 Oct 2007
Primary completion30 Sep 2008
Study completion31 Jan 2011

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Rheumatoid ArthritisStudies of the same condition, open and under way.
More trials run by Hoffmann-La RocheThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 132 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00535782
Sponsor's protocol ID: WA19923
Other IDs: 2007-001114-17
Status last verified: Jun 2017
First submitted: 24 Sep 2007
Last updated: 26 Jul 2017
Results posted: Yes, on ClinicalTrials.gov

Publications

Wang J, Bansal AT, Martin M, Germer S, Benayed R, Essioux L, Lee JS, Begovich A, Hemmings A, Kenwright A, Taylor KE, Upmanyu R, Cutler P, Harari O, Marchini J, Criswell LA, Platt A. Genome-wide association analysis implicates the involvement of eight loci with response to tocilizumab for the treatment of rheumatoid arthritis. Pharmacogenomics J. 2013 Jun;13(3):235-41. doi: 10.1038/tpj.2012.8. Epub 2012 Apr 10.
PubMed 22491018

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Active, not recruitingPhase 2
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All Rheumatoid Arthritis trials

Study at a glance

From the registry record, last updated by the sponsor on 26 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

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).
ClinicalTrials.gov ID: NCT00535782
Acronym / sponsor ID: WA19923
Conditions: Rheumatoid Arthritis
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 132 participants (actual)
Lead sponsor: Hoffmann-La RocheIndustry (pharma, biotech, devices)
Study start: 31 Oct 2007 (actual)
Primary completion: 30 Sep 2008 (actual)
Study completion: 31 Jan 2011 (actual)
First posted: 26 Sep 2007 (estimated)
Results: Posted 14 Nov 2012

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, investigator)
Number of arms: 2

Arm	Type	Receives
TCZ + MTX	Experimental	Drug: Tocilizumab, Drug: MethotrexateParticipants 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.
Placebo + MTX	Placebo comparator	Drug: Tocilizumab, Drug: Placebo, Drug: MethotrexateParticipants 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.

Who may qualify

Ages: 18 to 75 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (5 listed)

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

Key exclusion criteria (4 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
TocilizumabAlso: RoActemra, ActemraAdministered by intravenous infusion, 8 mg/kg every 4 weeks.	Drug	Placebo + MTX, TCZ + MTX
PlaceboPlacebo to tocilizumab administered by intravenous infusion every 4 weeks.	Drug	Placebo + MTX
MethotrexateAdministered orally or parenterally, 7.5-25 mg weekly.	Drug	Placebo + MTX, TCZ + MTX

Primary outcome

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.
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.

3 secondary outcomes

Change From Baseline to Week 24 in Small Low Density Lipoprotein (sLDL) Particle Numbers
Time frame: Baseline and Week 24
Change From Baseline to Week 24 in Aortic Pulse Wave Velocity (PWV)
Time frame: Baseline and Week 24
Number of Participants Experiencing Adverse Events (AEs)
Time frame: Up to Week 24

Results and safety

Results posted to the registry on 14 Nov 2012, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Part 1: TCZ + MTX	69	65
Part 1: Placebo + MTX	63	59
Part 2: TCZ + MTX	0	0

Primary outcome: Change From Baseline in Small Low Density Lipoprotein (sLDL) Particle Numbers

Time frame: Baseline and Week 12. Mean (Standard Deviation). Unit: nmol/L

Measure	TCZ + MTX n = 69	Placebo + MTX n = 63
Baseline (n=63, 59)	737.79 (467.097)	792.78 (392.051)
Week 12 (n=69, 63)	768.04 (628.281)	777.71 (394.527)
Change from Baseline at Week 12 (n=63, 59)	23.73 (368.273)	22.41 (237.476)

Population analysed: Intent to treat (ITT) population. All randomized patients who received any part of an infusion of study medication are included. Patients who received an incorrect therapy from that intended are summarized in the group according to the intended randomized treatment group. Last observation carried forward (LOCF) imputation was used.

Primary outcome: Change From Baseline to Week 12 in Aortic Pulse Wave Velocity (PWV)

Time frame: Baseline and Week 12. Mean (Standard Deviation). Unit: meters/second

Measure	TCZ + MTX n = 69	Placebo + MTX n = 63
Baseline (n=69, 59)	8.97 (1.970)	9.01 (2.519)
Week 12 (n=69, 62)	8.94 (2.510)	8.39 (1.836)
Change from Baseline at Week 12 (n=69, 59)	-0.03 (1.970)	-0.68 (1.741)

3 secondary outcomes are reported in the full results.

Adverse events

Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Part 1: TCZ + MTX	3 of 70 (4.3%)	59 of 70 (84.3%)	Not reported
Part 1: Placebo + MTX	2 of 62 (3.2%)	44 of 62 (71%)	Not reported
All TCZ + MTX	30 of 130 (23.1%)	124 of 130 (95.4%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 26 Jul 2017.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 22491018Wang J, Bansal AT, Martin M, Germer S, Benayed R, Essioux L, Lee JS, Begovich A, Hemmings A, Kenwright A, Taylor KE, Upmanyu R, Cutler P, Harari O, Marchini J, Criswell LA, Platt A. Genome-wide association analysis implicates the involvement of eight loci with response to tocilizumab for the treatment of rheumatoid arthritis. Pharmacogenomics J. 2013 Jun;13(3):235-41. doi: 10.1038/tpj.2012.8. Epub 2012 Apr 10.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Clinical Trials study director

Hoffmann-La Roche

40 sites in 4 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Tocilizumab and Methotrexate in people with Rheumatoid Arthritis, run by Hoffmann-La Roche at 40 sites in 4 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 26 Jul 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 40 sites in United States, Canada, United Kingdom, Puerto Rico. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 14 Nov 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change From Baseline in Small Low Density Lipoprotein (sLDL) Particle Numbers (time frame: Baseline and Week 12). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00535782, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Jul 2017.