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)

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Janssen Research & Development, LLC
Sponsor:
Collaborator:
GlaxoSmithKline
Information provided by (Responsible Party):
Janssen Research & Development, LLC
ClinicalTrials.gov Identifier:
NCT01606761
First received: May 24, 2012
Last updated: July 14, 2014
Last verified: July 2014
  Purpose

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.


Condition Intervention Phase
Arthritis, Rheumatoid
Drug: Placebo
Drug: Sirukumab
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Janssen Research & Development, LLC:

Primary Outcome Measures:
  • Proportion of patients with an ACR 20 response [ Time Frame: Week 16 ] [ Designated as safety issue: No ]
    ACR 20 response is a 20% improvement in rheumatoid arthritis (RA) symptoms.


Secondary Outcome Measures:
  • Change from baseline in HAQ-DI [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    The Health Assessment Questionnaire-Disability Index (HAQ-DI) assesses the degree of difficulty a person has in accomplishing tasks in 8 functional areas, each scored from 0 (no difficulty) to 3 (inability to perform a task).

  • Proportion of patients with an ACR 50 response [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    ACR 50 response is a 50% improvement in RA symptoms.

  • Proportion of patients with DAS28 (CRP) remission [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    DAS28 (using CRP [C-reactive protein]) remission is defined as a value of <2.6 on the Disease Activity Index, a measure of tender and swollen joints and the patient's and physician's assessments of disease activity.

  • Pharmacogenetics (deoxyribonucleic acid [DNA]) Evaluations [ Time Frame: Week 0 ] [ Designated as safety issue: No ]
    Genomic testing will be done on blood samples of patients who have consented, to search for links of specific genes to disease or response to drug.

  • Health economics evaluations [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
    Data will be collected about patient employability, daily work productivity, and time lost from work.

  • Plasma concentrations of sirukumab [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
    Plasma concentrations of sirukumab will be used to determine pharmacokinetic parameters for sirukumab (measurements describing how the body affects the drug).


Estimated Enrollment: 840
Study Start Date: August 2012
Estimated Study Completion Date: April 2016
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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: 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.
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=100, form=solution for injection, route=subcutaneous use; Weeks 0, 2, and every 2 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; Weeks 2, 6, and every 4 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.

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01606761

Contacts
Contact: Use link at the bottom of the page to see if you qualify for an enrolling site (see list). If you still have questions: JNJ.CT@sylogent.com

  Show 263 Study Locations
Sponsors and Collaborators
Janssen Research & Development, LLC
GlaxoSmithKline
Investigators
Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC
  More Information

Additional Information:
No publications provided

Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT01606761     History of Changes
Other Study ID Numbers: CR100864, CNTO136ARA3003, 2010-022243-38, U1111-1135-6365
Study First Received: May 24, 2012
Last Updated: July 14, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Janssen Research & Development, LLC:
Arthritis, Rheumatoid
Active rheumatoid arthritis despite anti-TNF-alpha therapy
Sirukumab
Human Anti-IL-6 monoclonal antibody

Additional relevant MeSH terms:
Arthritis, Rheumatoid
Arthritis
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Antibodies
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 20, 2014