Clinical trial NCT01606761: 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)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Arthritis, Rheumatoid
Keywords: Arthritis, Rheumatoid
Active rheumatoid arthritis despite anti-TNF-alpha therapy
Sirukumab
Human Anti-IL-6 monoclonal antibody
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
Collaborators: name: GlaxoSmithKline
First posted: 2012-05-28
Enrollment: 878
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Percentage of Participants Achieving American College of Rheumatology (ACR) 20 Response at Week 16
timeFrame: Week 16
Secondary outcomes:
measure: Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) Score at Week 24
timeFrame: Baseline and Week 24
measure: Percentage of Participants Achieving American College of Rheumatology (ACR) 50 Response at Week 24
timeFrame: Week 24
measure: Percentage of Participants With Disease Activity Index Score 28 (CRP) Remission at Week 24
timeFrame: Week 24
Other outcomes:
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country: Japan
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country: Korea, Republic of
city: Daegu
country: Korea, Republic of
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country: Korea, Republic of
city: Gwangju
country: Korea, Republic of
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country: Korea, Republic of
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country: Korea, Republic of
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country: Korea, Republic of
city: Seoul
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country: Lithuania
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country: Mexico
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country: Mexico
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country: Mexico
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country: Netherlands
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country: New Zealand
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city: Wellington
country: New Zealand
city: Bydgoszcz
country: Poland
city: Elblag
country: Poland
city: Lublin
country: Poland
city: Poznan
country: Poland
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country: Poland
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country: Poland
city: Coimbra
country: Portugal
city: Lisboa
country: Portugal
city: Lisbon
country: Portugal
city: San Juan
country: Puerto Rico
city: Barnaul
country: Russian Federation
city: Moscow N/A
country: Russian Federation
city: Moscow
country: Russian Federation
city: Novosibirsk
country: Russian Federation
city: Omsk
country: Russian Federation
city: Orenburg
country: Russian Federation
city: Ryazan
country: Russian Federation
city: Saint Petersburg
country: Russian Federation
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country: Russian Federation
city: Ulyanovsk
country: Russian Federation
city: Bilbao
country: Spain
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country: Spain
city: La Laguna
country: Spain
city: Madrid
country: Spain
city: Mérida
country: Spain
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country: Spain
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country: Spain
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country: Taiwan
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country: Taiwan
city: Taichung
country: Taiwan
city: Taipei
country: Taiwan
city: Barnsley
country: United Kingdom
city: London
country: United Kingdom
city: Middlesbrough
country: United Kingdom
city: Sheffield
country: United Kingdom
city: Wigan
country: United Kingdom
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References:
citation: 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.