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)

February 23, 2018 updated by: Janssen Research & Development, LLC

A Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel Group Study of CNTO 136 (Sirukumab), a Human Anti-IL-6 Monoclonal Antibody, Administered Subcutaneously, in Subjects With Active Rheumatoid Arthritis Despite Anti-TNF-Alpha Therapy

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

878

Phase

  • 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

  • Argentina
      • Ciudad Autónoma De Buenos Aires, Argentina
      • Rosario, Argentina
      • San Miguel De Tucuman, Argentina
  • Australia
      • Campbelltown, Australia
      • Victoria Park, Australia
  • Austria
      • Vienna, Austria
      • Wien, Austria
  • Belgium
      • Liège, Belgium
  • Canada
      • Burlington, Canada
      • Saint-John'S, Canada
      • Toronto N/A, Canada
    • British Columbia
      • Victoria, British Columbia, Canada
    • Manitoba
      • Winnipeg, Manitoba, Canada
    • Newfoundland and Labrador
      • St. John'S, Newfoundland and Labrador, Canada
    • Ontario
      • Kitchener, Ontario, Canada
  • Croatia
      • Zagreb, Croatia
  • France
      • Paris, France
      • Toulouse Cedex 9, France
  • Germany
      • Berlin, Germany
      • Dresden, Germany
      • Erfurt, Germany
      • Frankfurt/Main, Germany
      • Gÿttingen N/A, Germany
      • Hamburg, Germany
      • Herne, Germany
      • Kiel Kronshagen, Germany
      • Köln, Germany
      • Schwerin, Germany
      • Vogelsang-Gommern, Germany
      • Würzburg, Germany
      • Zerbst, Germany
  • Japan
      • Ayauta, Japan
      • Bunkyo-Ku, Japan
      • Fukuoka, Japan
      • Fukuyama, Japan
      • Higashihiroshima, Japan
      • Hiroshima, Japan
      • Izumo, Japan
      • Kagoshima, Japan
      • Kato, 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
  • Korea, Republic of
      • Busan, Korea, Republic of
      • Daegu, Korea, Republic of
      • Daejeon, Korea, Republic of
      • Gwangju, Korea, Republic of
      • Incheon, Korea, Republic of
      • Jeonju-Si, Korea, Republic of
      • Seongnam-Si, Korea, Republic of
      • Seoul, Korea, Republic of
      • Suwon, Korea, Republic of
  • Lithuania
      • Kaunas, Lithuania
      • Klaipeda, Lithuania
  • Mexico
      • Guadalajara, Mexico
      • Merida, Mexico
      • San Luis Potosí, Mexico
  • Netherlands
      • Sneek, Netherlands
  • New Zealand
      • Christchurch, New Zealand
      • Hamilton, New Zealand
      • Wellington, New Zealand
  • Poland
      • Bydgoszcz, Poland
      • Elblag, Poland
      • Lublin, Poland
      • Poznan, Poland
      • Ustron, Poland
      • Warszawa, Poland
  • Portugal
      • Coimbra, Portugal
      • Lisboa, Portugal
      • Lisbon, Portugal
  • Puerto Rico
      • San Juan, Puerto Rico
  • Russian Federation
      • Barnaul, Russian Federation
      • Moscow, Russian Federation
      • Moscow N/A, Russian Federation
      • Novosibirsk, Russian Federation
      • Omsk, Russian Federation
      • Orenburg, Russian Federation
      • Ryazan, Russian Federation
      • Saint Petersburg, Russian Federation
      • Saratov, Russian Federation
      • Ulyanovsk, Russian Federation
  • Spain
      • Bilbao, Spain
      • Coruña, Spain
      • La Laguna, Spain
      • Madrid, Spain
      • Mérida, Spain
      • Santander, Spain
      • Santiago De Compostela, Spain
  • Taiwan
      • Kaohsiung, Taiwan
      • Taichung, Taiwan
      • Taichung City, Taiwan
      • Taipei, Taiwan
  • United Kingdom
      • Barnsley, United Kingdom
      • London, United Kingdom
      • Middlesbrough, United Kingdom
      • Sheffield, United Kingdom
      • Wigan, United Kingdom
  • United States
    • Alabama
      • Birmingham, Alabama, United States
    • Arizona
      • Glendale, Arizona, United States
      • Mesa, Arizona, United States
      • Phoenix, Arizona, United States
    • California
      • 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
    • Connecticut
      • Hamden, Connecticut, United States
    • Florida
      • 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
    • Idaho
      • Boise, Idaho, United States
      • Idaho Falls, Idaho, United States
    • Indiana
      • Indianapolis, Indiana, United States
    • Iowa
      • Cedar Rapids, Iowa, United States
    • Kentucky
      • Bowling Green, Kentucky, United States
    • Louisiana
      • Monroe, Louisiana, United States
      • Shreveport, Louisiana, United States
    • Maryland
      • Cumberland, Maryland, United States
      • Frederick, Maryland, United States
      • Hagerstown, Maryland, United States
    • Minnesota
      • Eagan, Minnesota, United States
      • Rochester, Minnesota, United States
    • Mississippi
      • Flowood, Mississippi, United States
      • Tupelo, Mississippi, United States
    • Missouri
      • Saint Louis, Missouri, United States
      • Springfield, Missouri, United States
    • Nebraska
      • Omaha, Nebraska, United States
    • Nevada
      • Las Vegas, Nevada, United States
    • New Jersey
      • Freehold, New Jersey, United States
    • New Mexico
      • Albuquerque, New Mexico, United States
    • New York
      • Brooklyn, New York, United States
      • Lake Success, New York, United States
      • Plainview, New York, United States
    • North Carolina
      • Charlotte, North Carolina, United States
      • Hickory, North Carolina, United States
    • Ohio
      • Cincinnati, Ohio, United States
      • Columbus, Ohio, United States
      • Dayton, Ohio, United States
      • Middleburg Heights, Ohio, United States
    • Oklahoma
      • Edmond, Oklahoma, United States
      • Tulsa, Oklahoma, United States
    • Pennsylvania
      • Erie, Pennsylvania, United States
      • Pittsburgh, Pennsylvania, United States
      • Wyomissing, Pennsylvania, United States
    • Rhode Island
      • East Greenwich, Rhode Island, United States
    • South Carolina
      • Charleston, South Carolina, United States
    • Texas
      • 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
    • Washington
      • Kennewick, Washington, United States
      • Seattle, Washington, United States
    • West Virginia
      • Beckley, West Virginia, United States
      • Clarksburg, West Virginia, United States

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

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

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
Intervention / Treatment
Experimental: 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.
Drug: Placebo
Form=solution for injection, route=subcutaneous use; every 2 weeks from Week 0 through Week 22.
Drug: Placebo
Form=solution for injection, route=subcutaneous use; Weeks 2, 6, and every 4 weeks through Week 52.
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.
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.
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.
Experimental: Group 2
Patients will receive sirukumab 100 mg SC at Weeks 0, 2, and every 2 weeks through Week 52.
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.
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.
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.
Experimental: 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.
Drug: Placebo
Form=solution for injection, route=subcutaneous use; every 2 weeks from Week 0 through Week 22.
Drug: Placebo
Form=solution for injection, route=subcutaneous use; Weeks 2, 6, and every 4 weeks through Week 52.
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.
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.
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Participants Achieving American College of Rheumatology (ACR) 20 Response at Week 16
Time Frame: Week 16
The ACR 20 Response is defined as greater than or equal to (>=) 20 percent improvement in swollen joint count (66 joints) and tender joint count (68 joints) and >=20 percent improvement in 3 of following 5 assessments: patient's assessment of pain using Visual Analog Scale (VAS; 0-10 scale, 0 =no pain and 10 =worst possible pain), patient's global assessment of disease activity by using VAS (the scale ranges from 0 to 10, [0 =no pain to 10 =worst possible pain]), physician's global assessment of disease activity using VAS, participant's assessment of physical function measured by Health Assessment Questionnaire-Disability Index (HAQ-DI, defined as a 20-question instrument assessing 8 functional areas. The derived HAQ-DI ranges from 0, indicating no difficulty, to 3, indicating inability to perform a task in that area) and serum C-Reactive Protein (CRP).
Week 16

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) Score at Week 24
Time Frame: Baseline and Week 24
The HAQ-DI is a 20-question instrument that assesses the degree of difficulty a person has in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping and activities of daily living). Responses in each functional area are scored from 0 to 3 (0=no difficulty and 3=inability to perform a task in that area). Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0-3 where 0 = least difficulty and 3 = extreme difficulty.
Baseline and Week 24
Percentage of Participants Achieving American College of Rheumatology (ACR) 50 Response at Week 24
Time Frame: Week 24
The ACR 50 Response is defined as >= 50 percent improvement in swollen joint count (66 joints) and tender joint count (68 joints) and >=50 percent improvement in 3 of following 5 assessments: patient's assessment of pain using VAS ( 0-10 scale, 0 =no pain and 10 =worst possible pain), patient's global assessment of disease activity by using VAS (the scale ranges from 0 to 10, [0 =no pain to 10 =worst possible pain]), physician's global assessment of disease activity using VAS, participant's assessment of physical function measured by HAQ-DI (defined as a 20-question instrument assessing 8 functional areas. The derived HAQ-DI ranges from 0, indicating no difficulty, to 3, indicating inability to perform a task in that area) and serum C-Reactive Protein (CRP).
Week 24
Percentage of Participants With Disease Activity Index Score 28 (CRP) Remission at Week 24
Time Frame: Week 24
The Disease Activity Index Score 28 (DAS28) based on C-Reactive Protein (CRP) is a statistically derived index combining tender joints (28 joints), swollen joints (28 joints), CRP and patient's global assessment of disease activity. The set of 28 joint count is based on evaluation of the shoulder, elbow, wrist, metacarpophalangeal (MCP) MCP1 to MCP5, proximal interphalangeal (PIP) PIP1 to PIP5 joints of both the upper right extremity and the upper left extremity as well as the knee joints of lower right and lower left extremities. The values are 0=best to 10=worst. DAS28 (CRP) remission is defined as a DAS28 (CRP) value of less than (<) 2.6 at any study visit.
Week 24

Collaborators and Investigators

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

Sponsor

Janssen Research & Development, LLC

Collaborators

GlaxoSmithKline

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)

August 6, 2012

Primary Completion (Actual)

March 17, 2015

Study Completion (Actual)

January 12, 2016

Study Registration Dates

First Submitted

May 24, 2012

First Submitted That Met QC Criteria

May 24, 2012

First Posted (Estimate)

May 28, 2012

Study Record Updates

Last Update Posted (Actual)

March 23, 2018

Last Update Submitted That Met QC Criteria

February 23, 2018

Last Verified

February 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CR100864
  • CNTO136ARA3003 (Other Identifier: Janssen Research & Development, LLC)
  • 2010-022243-38 (EudraCT Number)
  • U1111-1135-6365 (Other Identifier: Universal Trial Number)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

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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