A Study of CNTO 136 (Sirukumab), Administered Subcutaneously, in Patients With Active Rheumatoid Arthritis Despite Disease-Modifying Antirheumatic Drug (DMARD) Therapy (SIRROUND) - Full Text View

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) and inhibition of radiographic progression in patients with active RA who are unresponsive to treatment with disease-modifying antirheumatic drugs (DMARD).

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 DMARD Therapy

Resource links provided by NLM:

MedlinePlus related topics: Rheumatoid Arthritis

U.S. FDA Resources

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.
Change from baseline in vdH-S score [ Time Frame: Week 52 ] [ Designated as safety issue: No ]
vdH-S is a measure of joint damage in the hands and feet and is scored from 0 (normal) to 448 (worst).

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.
Proportion of patients with major clinical response [ Time Frame: Week 52 ] [ Designated as safety issue: No ]
Major clinical response is defined as 70% improvement in RA symptoms for 6 continuous months during the study.
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.
Summary of C-trough values for sirukumab [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
C-trough is the observed serum concentration immediately prior to the next administration of sirukumab.
CL/F for sirukumab [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
Apparent total systemic clearance after extravascular administration
V/F for sirukumab [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
Apparent volume of distribution after extravascular administration

Estimated Enrollment:	1500
Study Start Date:	August 2012
Estimated Study Completion Date:	November 2016
Estimated Primary Completion Date:	July 2016 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Group 1	Drug: Placebo Form=solution for injection, route=subcutaneous use; every 2 weeks from Week 0 through Week 50. 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 52 through Week 104.
Experimental: Group 2	Drug: Sirukumab Type=exact, unit=mg, number=100, form=solution for injection, route=subcutaneous use; Weeks 0, 2, and every 2 weeks through Week 104.
Experimental: Group 3	Drug: Placebo Form=solution for injection, route=subcutaneous use; Weeks 2, 6, and every 4 weeks through Week 104. Drug: Sirukumab Type=exact, unit=mg, number=50, form=solution for injection, route=subcutaneous use; Weeks 0, 4, and every 4 weeks through Week 104.

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 120 weeks, which includes 104 weeks of treatment. Upon completion of participation through Week 104, patients will be eligible to enroll in a long-term safety and efficacy study. If they choose not to 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 52, 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 6 of 68 tender joints and 6 of 66 swollen joints, at screening and at baseline
Have been unresponsive to single-agent or combination disease-modifying antirheumatic drugs (DMARD) therapy that includes methotrexate (MTX) or sulfasalazine (SSZ) due to lack of benefit after at least 12 weeks of DMARD, as assessed by the treating physician
If using oral corticosteroids, must be on a stable dose equivalent 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 DMARD such as MTX, 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

Exclusion Criteria:

Has a history of intolerance to at least 2 or inadequate response to at least 1 anti-tumor necrosis factor alpha agent after 3 months of therapy
Has received infliximab, golimumab, adalimumab, or certolizumab pegol within 3 months of the first study agent administration
Has received etanercept or yisaipu within 6 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 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 4 weeks of first study agent administration
Has used any other biologic therapy for the treatment of RA within 3 months 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

Please refer to this study by its ClinicalTrials.gov identifier: NCT01604343

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 178 Study Locations

Sponsors and Collaborators

Janssen Research & Development, LLC

Investigators

Study Director:

Janssen Research & Development, LLC Clinical Trial

Janssen Research & Development, LLC

More Information

Additional Information:

To learn how to participate in this trial please click here. This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Janssen Research & Development, LLC
ClinicalTrials.gov Identifier:	NCT01604343 History of Changes
Other Study ID Numbers:	CR100866, CNTO136ARA3002, 2010-022242-24, U1111-1135-6325
Study First Received:	May 21, 2012
Last Updated:	May 9, 2013
Health Authority:	United States: Food and Drug Administration

Keywords provided by Janssen Research & Development, LLC:

Active rheumatoid arthritis despite disease-modifying antirheumatic drug therapy
Sirukumab
Human Anti-IL-6 monoclonal antibody

Additional relevant MeSH terms:

Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases

Immune System Diseases
Antirheumatic Agents
Antibodies, Monoclonal
Therapeutic Uses
Pharmacologic Actions
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on May 19, 2013