A Study of CNTO 136 (Sirukumab), a Human Anti-IL-6 Monoclonal Antibody, Administered Subcutaneously, in Patients With Active Rheumatoid Arthritis Despite Anti-TNF-Alpha Therapy (SIRROUND-T)

NCT ID: NCT01606761

Last Updated: 2018-03-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 878 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-08-06
• Study Completion Date: 2016-01-12

Brief Summary

The purpose of this study is to assess the efficacy of sirukumab as measured by the reduction of the signs and symptoms of rheumatoid arthritis (RA) in patients with active RA who are unresponsive or intolerant to treatment with anti-TNF-alpha agents.

Detailed Description

Patients will be randomly assigned to treatment groups, and they and study personnel will not know the identity of the treatments given. Some patients will receive a placebo, which resembles a medication, but does not contain an active substance. This helps to determine if the study agent is effective. Patients will receive placebo or sirukumab by injection under the skin. The expected duration of the study is 68 weeks, which includes 52 weeks of treatment. Participants who complete participation in the study will be eligible for inclusion into the long term extension study if enrollment at a participating site is available to them. If they do not participate in the long-term study, they will continue into the safety follow-up for approximately 16 weeks. The placebo-controlled portion of the study is through Week 24, when placebo patients will cross over to one of two sirukumab dose regimens. Patient safety will be monitored throughout the study.

Conditions

Arthritis, Rheumatoid

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Group 1

Patients will receive placebo every 2 weeks from Week 0 through Week 22, followed by a subcutaneous (SC) sirukumab dose regimen every 2 weeks through Week 52.

Group Type: EXPERIMENTAL

Placebo

Intervention Type: DRUG

Form=solution for injection, route=subcutaneous use; every 2 weeks from Week 0 through Week 22.

Sirukumab

Intervention Type: DRUG

Type=exact, unit=mg, number=50 or 100, form=solution for injection, route=subcutaneous use; every 2 weeks for 100 mg and every 4 weeks for 50 mg, Week 23 through Week 52.

Group 2

Patients will receive sirukumab 100 mg SC at Weeks 0, 2, and every 2 weeks through Week 52.

Group Type: EXPERIMENTAL

Sirukumab

Intervention Type: DRUG

Type=exact, unit=mg, number=100, form=solution for injection, route=subcutaneous use; Weeks 0, 2, and every 2 weeks through Week 52.

Group 3

Patients will receive sirukumab 50 mg SC at Weeks 0, 4, and every 4 weeks through Week 52. Between sirukumab injections, placebo SC administrations will be made at Weeks 2, 6, and every 4 weeks through Week 52.

Group Type: EXPERIMENTAL

Placebo

Intervention Type: DRUG

Form=solution for injection, route=subcutaneous use; Weeks 2, 6, and every 4 weeks through Week 52.

Sirukumab

Intervention Type: DRUG

Type=exact, unit=mg, number=50, form=solution for injection, route=subcutaneous use; Weeks 0, 4, and every 4 weeks through Week 52.

Interventions

Placebo

Form=solution for injection, route=subcutaneous use; every 2 weeks from Week 0 through Week 22.

Intervention Type: DRUG

Placebo

Form=solution for injection, route=subcutaneous use; Weeks 2, 6, and every 4 weeks through Week 52.

Intervention Type: DRUG

Sirukumab

Type=exact, unit=mg, number=50 or 100, form=solution for injection, route=subcutaneous use; every 2 weeks for 100 mg and every 4 weeks for 50 mg, Week 23 through Week 52.

Intervention Type: DRUG

Sirukumab

Type=exact, unit=mg, number=100, form=solution for injection, route=subcutaneous use; Weeks 0, 2, and every 2 weeks through Week 52.

Intervention Type: DRUG

Sirukumab

Type=exact, unit=mg, number=50, form=solution for injection, route=subcutaneous use; Weeks 0, 4, and every 4 weeks through Week 52.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Have a diagnosis of rheumatoid arthritis (RA) for at least 3 months before screening
• Have moderately to severely active RA with at least 4 of 68 tender joints and 4 of 66 swollen joints, at screening and at baseline
• Have had anti-tumor necrosis factor (TNF)-alpha therapy and were unresponsive by 1 of the following 2 reasons: Lack of benefit to at least 1 anti-TNF-alpha biologic therapy, as assessed by the treating physician, after at least 12 weeks of etanercept, yisaipu, adalimumab, golimumab, or certolizumab pegol therapy and/or at least a 14-week dosage regimen (ie, at least 4 doses) of infliximab; Intolerance to at least 2 anti-TNF-alpha biologic therapies, as assessed by the treating physician, to etanercept, yisaipu, adalimumab, golimumab, certolizumab pegol, or infliximab or have documented intolerance to an anti-TNF-alpha agent as described above that precludes further administration of anti-TNF-alpha agents
• If using oral corticosteroids, must be on a stable dose equivalent to less than or equal to 10 mg/day of prednisone for at least 2 weeks prior to the first administration of study agent. If currently not using corticosteroids, must not have received oral corticosteroids for at least 2 weeks prior to the first administration of study agent
• If using non nonsteroidal anti-inflammatory drug (NSAIDs) or other analgesics for RA, must be on a stable dose for at least 2 weeks prior to the first administration of study agent
• If using non-biologic disease modifying antirheumatic drugs (DMARDs) such as methotrexate (MTX), sulfasalazine (SSZ), hydroxychloroquine, chloroquine, or bucillamine, must be on a stable dose for at least 4 weeks prior to the first administration of study agent and should have no serious toxic side effects attributable to the DMARD
• C-reactive protein (CRP) 8.00 mg/L or more or erythrocyte sedimentation rate (ESR) 28 mm/hr or more at screening

Exclusion Criteria

• Has received infliximab, infliximab biosimilar, or golimumab intravenous (IV) within 8 weeks of the first study agent administration
• Has received subcutaneously (SC) golimumab, adalimumab, or certolizumab pegol within 6 weeks of the first study agent administration
• Has received etanercept or yisaipu within 4 weeks of the first study agent administration
• Has a history of intolerance to tocilizumab that precluded further treatment with it, or inadequate response to 3 months of tocilizumab (anti-IL-6 receptor) therapy. Has used tocilizumab within 8 weeks of the first study agent administration
• Has used B-cell-depleting therapy (eg, rituximab) within 7 months of first study agent administration or have evidence during screening of abnormally low B-cell level caused by previous B-cell depletion therapy
• Has used anakinra within 1 week of first study agent administration
• Has used abatacept or any other biologic therapy for the treatment of RA within 8 weeks of the first study agent administration
• Has received intra-articular (IA), intramuscular (IM), or IV corticosteroids for RA, including adrenocorticotrophic hormone during the 4 weeks prior to first study agent administration
• Has received leflunomide within 24 months before the first study agent administration and has not undergone a drug elimination procedure, unless the M1 metabolite is measured and is undetectable
• Has a history of cyclophosphamide or cytotoxic agent use
• Has received cyclosporine A, azathioprine, tacrolimus, mycophenolate mofetil, oral or parenteral gold, or D-penicillamine within 4 weeks of the first study agent administration
• Has received an investigational drug (including investigational vaccines) or used an investigational medical device within 3 months or 5 half-lives, whichever is longer, before the first study agent administration

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: collaborator

Janssen Research & Development, LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Janssen Research & Development, LLC Clinical Trial

Role: STUDY_DIRECTOR

Janssen Research & Development, LLC

Locations

Birmingham, Alabama, United States

Glendale, Arizona, United States

Mesa, Arizona, United States

Phoenix, Arizona, United States

Covina, California, United States

El Cajon, California, United States

Hemet, California, United States

Huntington Beach, California, United States

La Jolla, California, United States

La Palma, California, United States

Placentia, California, United States

Santa Monica, California, United States

Tustin, California, United States

Upland, California, United States

Victorville, California, United States

Whittier, California, United States

Hamden, Connecticut, United States

Aventura, Florida, United States

Boca Raton, Florida, United States

Brandon, Florida, United States

Daytona Beach, Florida, United States

Lake Mary, Florida, United States

Miami, Florida, United States

Naples, Florida, United States

Orlando, Florida, United States

Palm Harbor, Florida, United States

Plantation, Florida, United States

Sarasota, Florida, United States

Tampa, Florida, United States

Zephyrhills, Florida, United States

Boise, Idaho, United States

Idaho Falls, Idaho, United States

Indianapolis, Indiana, United States

Cedar Rapids, Iowa, United States

Bowling Green, Kentucky, United States

Monroe, Louisiana, United States

Shreveport, Louisiana, United States

Cumberland, Maryland, United States

Frederick, Maryland, United States

Hagerstown, Maryland, United States

Eagan, Minnesota, United States

Rochester, Minnesota, United States

Flowood, Mississippi, United States

Tupelo, Mississippi, United States

Springfield, Missouri, United States

St Louis, Missouri, United States

Omaha, Nebraska, United States

Las Vegas, Nevada, United States

Freehold, New Jersey, United States

Albuquerque, New Mexico, United States

Brooklyn, New York, United States

Lake Success, New York, United States

Plainview, New York, United States

Charlotte, North Carolina, United States

Hickory, North Carolina, United States

Cincinnati, Ohio, United States

Columbus, Ohio, United States

Dayton, Ohio, United States

Middleburg Heights, Ohio, United States

Edmond, Oklahoma, United States

Tulsa, Oklahoma, United States

Erie, Pennsylvania, United States

Pittsburgh, Pennsylvania, United States

Wyomissing, Pennsylvania, United States

East Greenwich, Rhode Island, United States

Charleston, South Carolina, United States

Austin, Texas, United States

Carrollton, Texas, United States

Corpus Christi, Texas, United States

Cypress, Texas, United States

Dallas, Texas, United States

Houston, Texas, United States

Katy, Texas, United States

Lubbock, Texas, United States

Mesquite, Texas, United States

Richmond, Texas, United States

Victoria, Texas, United States

Kennewick, Washington, United States

Seattle, Washington, United States

Beckley, West Virginia, United States

Clarksburg, West Virginia, United States

Buenos Aires, , Argentina

Rosario, , Argentina

San Miguel de Tucumán, , Argentina

Campbelltown, , Australia

Victoria Park, , Australia

Vienna, , Austria

Liège, , Belgium

Victoria, British Columbia, Canada

Winnipeg, Manitoba, Canada

St. John's, Newfoundland and Labrador, Canada

Kitchener, Ontario, Canada

Burlington, , Canada

St. John's, , Canada

Toronto, , Canada

Zagreb, , Croatia

Paris, , France

Toulouse, , France

Berlin, , Germany

Cologne, , Germany

Dresden, , Germany

Erfurt, , Germany

Frankfurt am Main, , Germany

Gÿttingen N/A, , Germany

Hamburg, , Germany

Herne, , Germany

Kiel Kronshagen, , Germany

Schwerin, , Germany

Vogelsang-Gommern, , Germany

Würzburg, , Germany

Zerbst, , Germany

Ayauta, , Japan

Bunkyō City, , Japan

Fukuoka, , Japan

Fukuyama, , Japan

Higashihiroshima, , Japan

Hiroshima, , Japan

Izumo, , Japan

Kagoshima, , Japan

Katō, , Japan

Kawagoe, , Japan

Kita-Gun, , Japan

Kumamoto, , Japan

Kurume, , Japan

Matsuyama, , Japan

Miyazaki, , Japan

Nagano, , Japan

Nagasaki, , Japan

Nagoya, , Japan

Nishimuro-Gun, , Japan

Nishinomiya, , Japan

Okayama, , Japan

Osaka, , Japan

Sapporo, , Japan

Sasebo, , Japan

Shibata, , Japan

Shimonoseki, , Japan

Shimotsuke, , Japan

Shinjuku-Ku, , Japan

Sumida-Ku, , Japan

Takaoka,Toyama, , Japan

Takasaki, , Japan

Tokorozawa, , Japan

Tokushima, , Japan

Tomakomai, , Japan

Tomishiro, , Japan

Tonami, , Japan

Tsu, , Japan

Ureshino, , Japan

Yokohama, , Japan

Kaunas, , Lithuania

Klaipėda, , Lithuania

Guadalajara, , Mexico

Mérida, , Mexico

San Luis Potosí City, , Mexico

Sneek, , Netherlands

Christchurch, , New Zealand

Hamilton, , New Zealand

Wellington, , New Zealand

Bydgoszcz, , Poland

Elblag, , Poland

Lublin, , Poland

Poznan, , Poland

Ustroń, , Poland

Warsaw, , Poland

Coimbra, , Portugal

Lisbon, , Portugal

San Juan, , Puerto Rico

Barnaul, , Russia

Moscow, , Russia

Novosibirsk, , Russia

Omsk, , Russia

Orenburg, , Russia

Ryazan, , Russia

Saint Petersburg, , Russia

Saratov, , Russia

Ulyanovsk, , Russia

Busan, , South Korea

Daegu, , South Korea

Daejeon, , South Korea

Gwangju, , South Korea

Incheon, , South Korea

Jeonju, , South Korea

Seongnam-si, , South Korea

Seoul, , South Korea

Suwon, , South Korea

A Coruña, , Spain

Bilbao, , Spain

Madrid, , Spain

Mérida, , Spain

San Cristóbal de La Laguna, , Spain

Santander, , Spain

Santiago de Compostela, , Spain

Kaohsiung City, , Taiwan

Taichung, , Taiwan

Taipei, , Taiwan

Barnsley, , United Kingdom

London, , United Kingdom

Middlesbrough, , United Kingdom

Sheffield, , United Kingdom

Wigan, , United Kingdom

Countries

United States; Argentina; Australia; Austria; Belgium; Canada; Croatia; France; Germany; Japan; Lithuania; Mexico; Netherlands; New Zealand; Poland; Portugal; Puerto Rico; Russia; South Korea; Spain; Taiwan; United Kingdom

References

Aletaha D, Bingham CO 3rd, Tanaka Y, Agarwal P, Kurrasch R, Tak PP, Popik S. Efficacy and safety of sirukumab in patients with active rheumatoid arthritis refractory to anti-TNF therapy (SIRROUND-T): a randomised, double-blind, placebo-controlled, parallel-group, multinational, phase 3 study. Lancet. 2017 Mar 25;389(10075):1206-1217. doi: 10.1016/S0140-6736(17)30401-4. Epub 2017 Feb 16.

Reference Type: DERIVED

PMID: 28215362 (View on PubMed)

Other Identifiers

CNTO136ARA3003

Identifier Type: OTHER

Identifier Source: secondary_id

2010-022243-38

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

U1111-1135-6365

Identifier Type: OTHER

Identifier Source: secondary_id

CR100864

Identifier Type: -

Identifier Source: org_study_id