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Rheumatoid ArthritisPhase 3ROSENCT00531817

A Study of Tocilizumab in Combination With DMARDs in Patients With Moderate to Severe Rheumatoid Arthritis

A Phase 3 study testing Tocilizumab and Permitted DMARDs in people with Rheumatoid Arthritis, run by Hoffmann-La Roche at 157 sites in 2 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

This 2-arm study assessed the safety and efficacy of tocilizumab versus placebo, both in combination with disease modifying antirheumatic drugs (DMARDs), in regard to reduction in signs and symptoms, in patients with moderate to severe active rheumatoid arthritis with an inadequate response to DMARDs. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Rheumatoid Arthritis
What is being tested?
Tocilizumab and Permitted DMARDs
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
619 participants
Where
157 sitesin 2 countries
Study dates
Oct 2007to Mar 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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Adult patients, ≥18 years of age
  • Active rheumatoid arthritis of >6 months duration
  • Received permitted DMARDs each at a stable dose for at least 7 weeks prior to baseline

Who cannot join

  • Rheumatic autoimmune disease or inflammatory joint disease other than rheumatoid arthritis
  • Major surgery within 8 weeks prior to screening or planned within 6 months following randomization
  • Unsuccessful treatment with a biologic agent, including an anti-TNF agent
  • Previous treatment with tocilizumab

Trial locations and contacts

157 sites in 2 countries.

157 sites in 2 countries

United States156 sites

  • Study site

    Akron, Ohio, 44333

  • Study site

    Amarillo, Texas, 79106

  • Study site

    Amarillo, Texas, 79124

  • Study site

    Atlanta, Georgia, 30342

  • Study site

    Baton Rouge, Louisiana, 70808

  • Study site

    Baton Rouge, Louisiana, 70810

  • Study site

    Beckley, West Virginia, 25801

  • Study site

    Beechwood, Ohio, 44122

  • Study site

    Bellaire, Texas, 77401

  • Study site

    Belmont, North Carolina, 28012

  • Study site

    Bethlehem, Pennsylvania, 10817

  • Study site

    Beverly Hills, California, 90211

  • Study site

    Billings, Montana, 59101

  • Study site

    Birmingham, Alabama, 35205

  • Study site

    Birmingham, Alabama, 35215

  • Study site

    Birmingham, Alabama, 35294-7201

  • Study site

    Blue Ridge, Georgia, 30513

  • Study site

    Boise, Idaho, 83702

  • Study site

    Bowling Green, Kentucky, 42102

  • Study site

    Burke, Virginia, 22015

  • Study site

    Burlington, Vermont, 05401

  • Study site

    Carrollton, Texas, 75007

  • Study site

    Charleston, South Carolina, 29407

  • Study site

    Charlotte, North Carolina, 28209

  • Study site

    Charlotte, North Carolina, 28210

  • Study site

    Clarksburg, West Virginia, 26301

  • Study site

    Colorado Springs, Colorado, 80910

  • Study site

    Columbia, South Carolina, 29204

  • Study site

    Crossville, Tennessee, 38555

  • Study site

    Dallas, Texas, 75231

  • Study site

    Dover, New Hampshire, 03820

  • Study site

    Downers Grove, Illinois, 60515

  • Study site

    Dunedin, Florida, 34698

  • Study site

    Durham, North Carolina, 27704

  • Study site

    Eagan, Minnesota, 55121

  • Study site

    Escondido, California, 92025

  • Study site

    Evansville, Indiana, 47714

  • Study site

    Florence, South Carolina, 29506

  • Study site

    Florissant, Missouri, 63031

  • Study site

    Flowood, Mississippi, 39232

  • Study site

    Fort Lauderdale, Florida, 33334

  • Study site

    Fort Valley, Georgia, 31030

  • Study site

    Fort Worth, Texas, 76107

  • Study site

    Freehold, New Jersey, 07728

  • Study site

    Grand Island, Nebraska, 68803

  • Study site

    Greensboro, North Carolina, 27408

  • Study site

    Greenville, North Carolina, 27834

  • Study site

    Greenville, South Carolina, 29601

  • Study site

    Hendersonville, Tennessee, 37073

  • Study site

    Hickory, North Carolina, 28601

  • Study site

    Houston, Texas, 77004

  • Study site

    Houston, Texas, 77034

  • Study site

    Houston, Texas, 77074

  • Study site

    Houston, Texas, 77090

  • Study site

    Idaho Falls, Idaho, 83404

  • Study site

    Jackson, Tennessee, 38305

  • Study site

    Jonesboro, Arkansas, 72401

  • Study site

    Kalamazoo, Michigan, 49009

  • Study site

    Kalispell, Montana, 59907

  • Study site

    Knoxville, Tennessee, 37909

  • Study site

    La Jolla, California, 92037

  • Study site

    Lake Havasu City, Arizona, 86403

  • Study site

    Lake Mary, Florida, 32746

  • Study site

    Lake Oswego, Oregon, 97035

  • Study site

    Las Vegas, Nevada, 89106

  • Study site

    Las Vegas, Nevada, 89128

  • Study site

    Leawood, Kansas, 66209

  • Study site

    Lexington, Kentucky, 40515

  • Study site

    Long Beach, California, 90815

  • Study site

    Los Angeles, California, 90095

  • Study site

    Mansfield, Massachusetts, 02048

  • Study site

    Mayfield, Ohio, 44143

  • Study site

    Melbourne, Florida, 32901

  • Study site

    Memphis, Tennessee, 38119

  • Study site

    Mesquite, Texas, 75150

  • Study site

    Miami, Florida, 33133

  • Study site

    Middleburg Heights, Ohio, 44130

  • Study site

    Milwaukee, Wisconsin, 53209

  • Study site

    Mineola, New York, 11501

  • Study site

    Missoula, Montana, 59802

  • Study site

    Monroe, Louisiana, 71203

  • Study site

    Montgomery, Alabama, 36111

  • Study site

    Munster, Indiana, 46321

  • Study site

    Myrtle Beach, South Carolina, 29572

  • Study site

    Nampa, Idaho, 83687

  • Study site

    Nashville, Tennessee, 37203

  • Study site

    New Brunswick, New Jersey, 08903

  • Study site

    New Orleans, Louisiana, 70112

  • Study site

    New York, New York, 10003

  • Study site

    New York, New York, 10029

  • Study site

    Norman, Oklahoma, 73069

  • Study site

    Ocala, Florida, 34474

  • Study site

    Oklahoma City, Oklahoma, 73103

  • Study site

    Oklahoma City, Oklahoma, 73104

  • Study site

    Onalaska, Wisconsin, 54605

  • Study site

    Orange Park, Florida, 32073

  • Study site

    Orchard Park, New York, 14127

  • Study site

    Orlando, Florida, 32804

  • Study site

    Palm Harbor, Florida, 34684

  • Study site

    Paradise Valley, Arizona, 85253

  • Study site

    Pasadena, California, 91107

  • Study site

    Passaic, New Jersey, 07055

  • Study site

    Peoria, Arizona, 85381

  • Study site

    Perrysburg, Ohio, 43551

  • Study site

    Philadelphia, Pennsylvania, 19102

  • Study site

    Philadelphia, Pennsylvania, 19152

  • Study site

    Pittsburgh, Pennsylvania, 15261

  • Study site

    Plantation, Florida, 33317

  • Study site

    Portland, Oregon, 97239

  • Study site

    Rapid City, South Dakota, 57701

  • Study site

    Rapid City, South Dakota, 57702

  • Study site

    Reno, Nevada, 89502

  • Study site

    Reston, Virginia, 22102

  • Study site

    Rock Hill, North Carolina, 29732

  • Study site

    Saint Clair Shores, Michigan, 48080

  • Study site

    Salem, Oregon, 97302

  • Study site

    Salem, Virginia, 24153

  • Study site

    Salt Lake City, Utah, 84132

  • Study site

    San Antonio, Texas, 78217

  • Study site

    San Antonio, Texas, 78229

  • Study site

    San Antonio, Texas, 78258

  • Study site

    Santa Maria, California, 93454

  • Study site

    Santa Monica, California, 90404

  • Study site

    Sarasota, Florida, 34239

  • Study site

    Scottsdale, Arizona, 85251

  • Study site

    Scottsdale, Arizona, 85258

  • Study site

    Seattle, Washington, 98133

  • Study site

    Seattle, Washington, 98195

  • Study site

    Sioux Falls, South Dakota, 57105

  • Study site

    Smithtown, New York, 11787

  • Study site

    South Bend, Indiana, 46601

  • Study site

    Spokane, Washington, 99204-2336

  • Study site

    Springfield, Illinois, 62704

  • Study site

    St Louis, Missouri, 63141

  • Study site

    Tamarac, Florida, 33321

  • Study site

    Tampa, Florida, 33609

  • Study site

    Teaneck, New Jersey, 07666

  • Study site

    Temple, Texas, 76508

  • Study site

    The Bronx, New York, 10451

  • Study site

    Tifton, Georgia, 311794

  • Study site

    Trumbull, Connecticut, 06611

  • Study site

    Tupelo, Mississippi, 38802

  • Study site

    Upland, California, 91786

  • Study site

    Van Nuys, California, 91405

  • Study site

    Waco, Texas, 76708

  • Study site

    Walnut Creek, California, 94598

  • Study site

    Washington D.C., District of Columbia, 20006

  • Study site

    Watertown, South Dakota, 57201

  • Study site

    Wausau, Wisconsin, 54401

  • Study site

    Wexford, Pennsylvania, 15090

  • Study site

    Wheaton, Maryland, 20902

  • Study site

    Whittier, California, 90606

  • Study site

    Willow Grove, Pennsylvania, 80045

  • Study site

    Worcester, Massachusetts, 01605

  • Study site

    Worcester, Massachusetts, 01610

  • Study site

    Zanesville, Ohio, 43701

Other trials in United States

Puerto Rico1 site

  • Study site

    San Juan, 00918

Other trials in Puerto Rico

About this study

Official title: A Randomized, Double-blind, Parallel-group Study to Evaluate the Safety and Efficacy of Tocilizumab (TCZ) Versus Placebo in Combination With Disease Modifying Antirheumatic Drugs (DMARDs) in Patients With Moderate to Severe Active Rheumatoid Arthritis (RA)

This 2-arm study assessed the safety and efficacy of tocilizumab versus placebo, both in combination with disease modifying antirheumatic drugs (DMARDs), in regard to reduction in signs and symptoms, in patients with moderate to severe active rheumatoid arthritis with an inadequate response to DMARDs. Patients were randomized in a ratio of 2:1 to receive either tocilizumab 8 mg/kg intravenously (IV) or placebo IV every 4 weeks. All patients also received stable antirheumatic therapy, including permitted DMARDs. The anticipated time on study treatment was 3-12 months and the target sample size was 500+ individuals.

Being tested
Tocilizumab, Placebo, Permitted DMARDs
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 Actemra, RoActemra

    Tocilizumab intravenously at a dose of 8 mg/kg over a 1-hour infusion, every 4 weeks, for a total of 6 infusions.

  • PlaceboDrug

    Placebo IV over a 1-hour infusion, every 4 weeks, for a total of 6 infusions.

  • Permitted DMARDsDrug

    As prescribed. The following DMARDs were permitted in this study: methotrexate (MTX), chloroquine, hydroxychloroquine, parenteral gold, sulfasalazine, azathioprine, and leflunomide. These DMARDs could be used alone or in combination, except for the combination of MTX and leflunomide, which was not allowed.

Study groups in NCT00531817
Study groupRoleWhat they receive
Tocilizumab 8 mg/kg + DMARDsExperimentalNot described
Receives: Drug: Tocilizumab; Drug: Permitted DMARDs
Placebo + DMARDsPlacebo comparatorNot described
Receives: Drug: Placebo; Drug: Permitted DMARDs

What is being measured

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

  1. Percentage of Patients With an Improvement of at Least 50% in American College of Rheumatology (ACR) Score (ACR50) From Baseline at Week 24

    Improvement must be seen in tender and swollen joint counts and in at least 3 of the following 5 parameters. Patient and physician assessment of patient disease activity (DA) in previous 24 hours on a visual analog scale (VAS, no DA to maximum DA); patient assessment of pain in previous 24 hours on a VAS (none to unbearable); Health Assessment Questionnaire-Disability Index (20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, 0=without difficulty to 3=unable to do); and C-reactive protein or, if missing, erythrocyte sedimentation rate.

    Measured: Baseline to Week 24

Secondary outcomes (10)

  1. Percentage of Patients With an Improvement of at Least 20%, 50%, or 70% in American College of Rheumatology (ACR) Score (ACR20, ACR50, ACR70) From Baseline at Weeks 4, 8, 12, 16, 20, and 24

    Improvement must be seen in tender and swollen joint counts and in at least 3 of the following 5 parameters. Patient and physician assessment of patient disease activity (DA) in previous 24 hours on a visual analog scale (VAS, no DA to maximum DA); patient assessment of pain in previous 24 hours on a VAS (none to unbearable); Health Assessment Questionnaire-Disability Index (20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, 0=without difficulty to 3=unable to do); and C reactive protein or, if missing, erythrocyte sedimentation rate.

    Measured: Baseline to Weeks 4, 8, 12, 16, 20, 24

  2. Mean Change From Baseline in Disease Activity Score 28 (DAS28) at Weeks 4, 8, 12, 16, 20, and 24

    DAS28 was calculated using the following formula: 0.56 × sqrt(TJC) + 0.28 × sqrt(SJC) + 0.70 × ln(ESR) + 0.014 × GH, where TJC = tender joint count on 28 joints, SJC = swollen joint count on 28 joints, ESR = erythrocyte sedimentation rate at the current visit (mm/hr), and GH = general health, ie, the patient's global assessment of disease activity (DA) in the previous 24 hours on a 100 mm visual analog scale (no DA to maximum DA). The DAS28 score ranges from 0 to 10, with higher scores indicating more rheumatoid arthritis. A negative change score indicates improvement.

    Measured: Baseline to Weeks 4, 8, 12, 16, 20, 24

  3. Percentage of Patients With European League Against Rheumatism (EULAR) Good, Moderate, or no Response at Weeks 4, 8, 12, 16, 20, and 24

    Change of the DAS28 score from baseline was used to determine the EULAR responses of good, moderate, or no response. For a post-baseline score ≤ 3.2, a change from baseline of < -1.2 was a good response, < -0.6 to ≥ -1.2 was a moderate response, and ≥ -0.6 was no response. For a post-baseline score > 3.2 to ≤ 5.1, a change from baseline of < -0.6 was a moderate response and ≥ -0.6 was no response. For a post-baseline score > 5.1, a change from baseline < -1.2 was a moderate response and ≥ -1.2 was no response. A good response could not be achieved for post-baseline scores > 3.2.

    Measured: Baseline to Weeks 4, 8, 12, 16, 20, and 24

  4. Mean Change From Baseline in the Routine Assessment Patient Index Data (RAPID) Score at Weeks 4, 8, 12, 16, 20, and 24

    Derived from the Multidimensional Health Assessment Questionnaire (MDHAQ), the RAPID includes 3 domains that assess disease activity in rheumatoid arthritis: A physical function score (MDHAQ items 1a-j), a pain visual analog scale score (VAS, item 2 in the MDHAQ), and a global assessment of disease activity VAS score (item 6 in the MDHAQ). Each domain is scored on a scale of 0-10. The RAPID score is the sum of the 3 domain scores divided by 3 resulting in a total score on a scale of 0-10. Higher scores indicate more disease activity and a negative change from baseline indicates improvement.

    Measured: Baseline to Weeks 4, 8, 12, 16, 20, and 24

  5. Mean Change From Baseline in 12-Item Short Form Health Survey v2 (SF-12) Scores at Weeks 4, 8, 12, 16, 20, and 24

    The SF-12 is a self-report measure of general health status with 1 or 2 items for each of 8 domains: Physical functioning, role limitations due to physical health problems, bodily pain, general health, vitality, social functioning, role limitations due to emotional problems, and mental health. Two component summaries, physical (PCS-12) and mental (MCS-12) were calculated using norm-based scoring, resulting in means of 50 and standard deviations of 10 in the 1998 general United States population. Higher scores represent better health and a positive change from baseline represents improvement.

    Measured: Baseline to Weeks 4, 8, 12, 16, 20, and 24

  6. Mean Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score at Weeks 4, 8, 12, 16, 20, and 24

    The FACIT-F is a 13-item patient self-report questionnaire that assesses fatigue over the previous 7 days by scoring each item on a 5-point scale (0=Not at all, 1=A little bit, 2=Somewhat, 3=Quite a bit, 4=Very much). An overall FACIT-F score was obtained by summing the scores of all 13 items. The overall score ranged from 0 to 52. A lower score indicates less fatigue. A negative change score indicates improvement.

    Measured: Baseline to Weeks 4, 8, 12, 16, 20, and 24

  7. Mean Change From Baseline in the Medical Outcomes Study (MOS) Sleep Scale Score at Weeks 4, 8, 12, 16, 20, and 24

    The MOS Sleep Scale is a 12-item patient self-report instrument that assesses the quality and quantity of sleep over the previous 4 weeks. A sleep problems index (SLP9) was generated using 9 of the 12 items (1, 3, 4, 5, 6, 7, 8, 9, 12). Each item was normalized so that the lowest and highest possible scores were set to 0 and 100, respectively. The SLP9 score is the average of the recoded 9 items. The SLP9 score ranged from 0 to 100. Higher scores represent greater sleep problems. A negative change score indicates improvement.

    Measured: Baseline to Weeks 4, 8, 12, 16, 20, and 24

  8. Mean Change From Baseline in Individual Components of the Routine Assessment Patient Index Data (RAPID) at Each Day During the First 7 Days of Treatment

    Derived from the Multidimensional Health Assessment Questionnaire (MDHAQ), the RAPID includes 3 domains that assess disease activity in rheumatoid arthritis: A physical function score (0-10), a pain visual analog scale score (VAS, 0-100), and a global assessment of disease activity VAS score (0-100). Each domain was assessed with the Patient Take Home Form (PTHF). Higher scores indicate more disease activity. A negative change score indicates improvement.

    Measured: Baseline through Day 7

  9. Percentage of Patients With an Improvement of at Least 20%, 50%, or 70% in American College of Rheumatology (ACR) Score (ACR20, ACR50, ACR70) From Baseline at Day 7

    Improvement must be seen in tender and swollen joint counts and in at least 3 of the following 5 parameters. Patient and physician assessment of patient disease activity (DA) in previous 24 hours on a visual analog scale (VAS, no DA to maximum DA); patient assessment of pain in previous 24 hours on a VAS (none to unbearable); Health Assessment Questionnaire-Disability Index (20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, 0=without difficulty to 3=unable to do); and C reactive protein or, if missing, erythrocyte sedimentation rate.

    Measured: Baseline to Day 7

  10. Mean Change From Baseline in C-reactive Protein (CRP) at Days 3 and 7

    Serum concentration of CRP (high-sensitivity CRP [hsCRP] test) was analyzed by a central laboratory.

    Measured: Baseline to Days 3 and 7

Timeline

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

  1. First posted19 Sep 2007 (estimated)
  2. Study startOct 2007
  3. Primary completionJun 2009
  4. Study completionMar 2011

Resources

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
619 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00531817
Sponsor's protocol ID
ML21136
Acronym
ROSE
Status last verified
Aug 2012
First submitted
18 Sep 2007
Last updated
20 Aug 2012

Publications

  • Yazici Y, Curtis JR, Ince A, Baraf HS, Lepley DM, Devenport JN, Kavanaugh A. Early effects of tocilizumab in the treatment of moderate to severe active rheumatoid arthritis: a one-week sub-study of a randomised controlled trial (Rapid Onset and Systemic Efficacy [ROSE] Study). Clin Exp Rheumatol. 2013 May-Jun;31(3):358-64. Epub 2013 Jan 10.

    PubMed 23305631

  • Yazici Y, Curtis JR, Ince A, Baraf H, Malamet RL, Teng LL, Kavanaugh A. Efficacy of tocilizumab in patients with moderate to severe active rheumatoid arthritis and a previous inadequate response to disease-modifying antirheumatic drugs: the ROSE study. Ann Rheum Dis. 2012 Feb;71(2):198-205. doi: 10.1136/ard.2010.148700. Epub 2011 Sep 26.

    PubMed 21949007

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Tocilizumab and Permitted DMARDs in people with Rheumatoid Arthritis, run by Hoffmann-La Roche at 157 sites in 2 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 3 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 20 Aug 2012. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 157 sites in United States, 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 4 Aug 2010). 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?

Percentage of Patients With an Improvement of at Least 50% in American College of Rheumatology (ACR) Score (ACR50) From Baseline at Week 24 (time frame: Baseline to Week 24). 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 NCT00531817, which also lists 2 linked publications.

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 20 Aug 2012.

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