Clinical trial NCT01604343: A Study of CNTO 136 (Sirukumab), Administered Subcutaneously, in Patients With Active Rheumatoid Arthritis Despite Disease-Modifying Antirheumatic Drug (DMARD) Therapy (SIRROUND-D)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Arthritis, Rheumatoid
Keywords: Active rheumatoid arthritis despite disease-modifying antirheumatic drug therapy
Sirukumab
Human Anti-IL-6 monoclonal antibody
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
Collaborators: name: GlaxoSmithKline
First posted: 2012-05-23
Enrollment: 1670
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) and inhibition of radiographic progression in patients with active RA who are unresponsive to treatment with disease-modifying antirheumatic drugs (DMARD).

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. Participants who complete participation in the study will be eligible for inclusion into the long-term safety and efficacy 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 52, 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 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 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 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 intravenous (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 have not undergone a drug elimination procedure, unless the M1 metabolite is measured and is undetectable. If a drug elimination procedure is performed during screening, the M1 metabolite should be measured and found to be 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 With an American College of Rheumatology (ACR) 20 Response at Week 16
timeFrame: Week 16
measure: Change From Baseline in Van Der Heijde-modified Sharpe (vdH-S) Score at Week 52
timeFrame: Baseline, Week 52
Secondary outcomes:
measure: Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Week 24
timeFrame: Baseline, Week 24
measure: Percentage of Participants With an American College of Rheumatology (ACR) 50 Response at Week 24
timeFrame: Week 24
measure: Percentage of Participants With Disease Activity Index Score 28 (DAS28) (C-reactive Protein (CRP) Remission at Week 24
timeFrame: Week 24
measure: Percentage of Participants With Major Clinical Response (MCR) at Week 52
timeFrame: Week 52
measure: Percentage of Participants With an American College of Rheumatology (ACR) 20 Response Through Week 52
timeFrame: Week 2, 4, 6, 8, 12, 18, 20, 24, 28, 32, 36, 40, 44, 48, and 52
measure: Percentage of Participants With an American College of Rheumatology (ACR) 50 Response
timeFrame: Week 2, 4, 6, 8, 12, 16, 18, 20, 28, 32, 36, 40, 44, 48 and 52
measure: Percentage of Participants With an American College of Rheumatology (ACR) 70 Response Through Week 52
timeFrame: Week 2, 4, 6, 8, 12, 16, 18, 20, 24, 28, 32, 36, 40, 44, 48 and 52
measure: Percentage of Participants With an American College of Rheumatology (ACR) 90 Response Through Week 52
timeFrame: Week 2, 4, 6, 8, 12, 16, 18, 20, 24, 28, 32, 36, 40, 44, 48 and 52
measure: Percentage of Participants With Disease Activity Index Score 28 (DAS28) C-reactive Protein (CRP) Response Through Week 52
timeFrame: Week 2, 4, 6, 8, 12, 16, 18, 20, 24, 28, 32, 36, 40, 44, 48 and 52
measure: Change From Baseline in Disease Activity Index Score 28 (DAS28) C-reactive Protein (CRP) Through Week 52
timeFrame: Baseline, Week 2, 4, 6, 8, 12, 16, 18, 20, 24, 28, 32, 36, 40, 44, 48 and 52
measure: Percentage of Participants With Disease Activity Index Score 28 (DAS28) (C-reactive Protein (CRP) Remission Through Week 52
timeFrame: Week 2, 4, 6, 8, 12, 16, 18, 20, 28, 32, 36, 40, 44, 48 and 52
measure: Change From Baseline in Simplified Disease Activity Index (SDAI) Score Through Week 52
timeFrame: Baseline, Week 2, 4, 6, 8, 12, 16, 18, 20, 24, 28, 32, 36, 40, 44, 48 and 52
measure: Change From Baseline in Clinical Disease Activity Index (CDAI) Score Through Week 52
timeFrame: Baseline, Week 2, 4, 6, 8, 12, 16, 18, 20, 24, 28, 32, 36, 40, 44, 48 and 52
measure: Percentage of Participants With Simplified Disease Activity Index Based (SDAI-based) American College of Rheumatology (ACR)/ European League Against Rheumatism (EULAR) Remission Through Week 52
timeFrame: Week 2, 4, 6, 8, 12, 16, 18, 20, 24, 28, 32, 36, 40, 44, 48 and 52
measure: Percentage of Participants With Boolean-based American College of Rheumatology (ACR)/ European League Against Rheumatism (EULAR) Remission Through Week 52
timeFrame: Week 2, 4, 6, 8, 12, 16, 18, 20, 24, 28, 32, 36, 40, 44, 48 and 52
measure: Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score Through Week 52
timeFrame: Baseline, Week 2, 4, 6, 8, 12, 16, 18, 20, 28, 32, 36, 40, 44, 48 and 52
measure: Area Under the Curve (AUC) of Change From Baseline in HAQ-DI Score From Week 0 Through Week 24 and From Week 0 Through Week 52
timeFrame: Week 0 Through Week 24 and 52
measure: Percentage of Participants With Health Assessment Questionnaire-Disability Index (HAQ-DI) Response Through Week 52
timeFrame: Week 2, 4, 6, 8, 12, 16, 18, 20, 24, 28, 32, 36, 40, 44, 48 and 52
measure: Percentage of Participants With Health Assessment Questionnaire-Disability Index (HAQ-DI) Score of Less Than or Equal to 0.5
timeFrame: Week 2, 4, 6, 8, 12, 16, 18, 20, 24, 28, 32, 36, 40, 44, 48 and 52
measure: Change From Baseline in Van Der Heijde-modified Sharpe (vdH-S) Score at Week 24
timeFrame: Baseline, Week 24
measure: Change From Baseline in Van Der Heijde-modified Sharpe (vdH-S) Sub-score by Type of Damage (Erosion or JSN) at Week 24 and 52
timeFrame: Baseline, Week 24 and 52
measure: Change From Baseline in Van Der Heijde-modified Sharpe (vdH-S) Sub-score by Region Hand or Feet and Type Erosion or JSN at Week 24 and 52
timeFrame: Baseline, Week 24 and 52
measure: Percentage of Participants With Change From Baseline in Van Der Heijde Modified Sharpe Score (vdH-S Score) Greater Than Smallest Detectable Change (SDC) at Weeks 24 and 52
timeFrame: Weeks 24 and 52
measure: Percentage of Participants With a Change of Less Than or Equal to 0 From Baseline in Van Der Heijde Modified Sharpe (vdH-S) Score at Weeks 24 and 52
timeFrame: Week 24 and 52
measure: Change From Baseline in Van Der Heijde Modified Sharpe Score (vdH-S Score) by Reader at Weeks 24 and 52
timeFrame: Baseline, Weeks 24 and 52
measure: Change From Baseline in Serum C-reactive Protein (CRP) Levels Through Week 52
timeFrame: Baseline, Week 2, 4, 6, 8, 12, 16, 18, 20, 24, 28, 32, 36, 40, 44, 48 and 52
measure: Change From Baseline in the Duration of Morning Stiffness Through Week 52
timeFrame: Baseline, Week 2, 4, 6, 8, 12, 16, 18, 20, 24, 28, 32, 36, 40, 44, 48 and 52
measure: Change From Baseline in Physical and Mental Component Summary Scores of 36-Item Short Form Health Survey (SF-36) at Weeks 24 and 52
timeFrame: Baseline, Week 24 and 52
measure: Percentage of Participants With Greater Than or Equal to 4-Point Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Score at Week 8, 16, 24, 36 and 52
timeFrame: Week 8, 16, 24, 36 and 52
measure: Change From Baseline in Total Scores of Work Limitations Questionnaire (WLQ) Week 8, 16, 24, 36 and 52
timeFrame: Baseline, Week 8, 16, 24, 36 and 52
measure: Change From Baseline in EuroQol Health State Visual Analogue Scale (EQ VAS)
timeFrame: Baseline, Week 8, 16, 24, 36 and 52
measure: Change From Baseline in EuroQol EQ-5D-3L Descriptive System
timeFrame: at Week 8, 16, 24, and 52
Other outcomes:
Locations:
city: Glendale
country: United States
state: Arizona
city: Mesa
country: United States
state: Arizona
city: Peoria
country: United States
state: Arizona
city: Phoenix
country: United States
state: Arizona
city: Covina
country: United States
state: California
city: El Cajon
country: United States
state: California
city: Glendale
country: United States
state: California
city: Hemet
country: United States
state: California
city: Huntington Beach
country: United States
state: California
city: La Jolla
country: United States
state: California
city: La Palma
country: United States
state: California
city: Whittier
country: United States
state: California
city: Aventura
country: United States
state: Florida
city: Brandon
country: United States
state: Florida
city: Daytona Beach
country: United States
state: Florida
city: Lake Mary
country: United States
state: Florida
city: Naples
country: United States
state: Florida
city: Palm Harbor
country: United States
state: Florida
city: Tampa
country: United States
state: Florida
city: Zephyrhills
country: United States
state: Florida
city: Indianapolis
country: United States
state: Indiana
city: Cedar Rapids
country: United States
state: Iowa
city: Bowling Green
country: United States
state: Kentucky
city: Monroe
country: United States
state: Louisiana
city: Wheaton
country: United States
state: Maryland
city: Eagan
country: United States
state: Minnesota
city: Saint Louis
country: United States
state: Missouri
city: Springfield
country: United States
state: Missouri
city: Omaha
country: United States
state: Nebraska
city: Albuquerque
country: United States
state: New Mexico
city: Brooklyn
country: United States
state: New York
city: Plainview
country: United States
state: New York
city: Charlotte
country: United States
state: North Carolina
city: Cincinnati
country: United States
state: Ohio
city: Middleburg Heights
country: United States
state: Ohio
city: Edmond
country: United States
state: Oklahoma
city: Tulsa
country: United States
state: Oklahoma
city: Duncansville
country: United States
state: Pennsylvania
city: Wyomissing
country: United States
state: Pennsylvania
city: Carrollton
country: United States
state: Texas
city: Corpus Christi
country: United States
state: Texas
city: Dallas
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: Lubbock
country: United States
state: Texas
city: Mesquite
country: United States
state: Texas
city: Kennewick
country: United States
state: Washington
city: Beckley
country: United States
state: West Virginia
city: Clarksburg
country: United States
state: West Virginia
city: Plovdiv
country: Bulgaria
city: Sofia
country: Bulgaria
city: Victoria
country: Canada
state: British Columbia
city: Winnipeg
country: Canada
state: Manitoba
city: Ottawa
country: Canada
state: Ontario
city: Burlington
country: Canada
city: Edmonton
country: Canada
city: Rancagua
country: Chile
city: Santiago
country: Chile
city: Valdivia
country: Chile
city: Bogotá
country: Colombia
city: Chia
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city: Medellín
country: Colombia
city: Osijek
country: Croatia
city: Rijeka
country: Croatia
city: Zagreb
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city: Ayauta-Gun
country: Japan
city: Bunkyo-Ku
country: Japan
city: Fukuoka
country: Japan
city: Higashihiroshima
country: Japan
city: Izumo
country: Japan
city: Kagoshima
country: Japan
city: Kato
country: Japan
city: Kawagoe
country: Japan
city: Kita-Gun
country: Japan
city: Kumamoto
country: Japan
city: Kurume
country: Japan
city: Miyazaki
country: Japan
city: Nagano
country: Japan
city: Nagasaki
country: Japan
city: Nagoya
country: Japan
city: Osaka
country: Japan
city: Sapporo
country: Japan
city: Sasebo
country: Japan
city: Shimonoseki
country: Japan
city: Shimotsuke
country: Japan
city: Shinjuku-Ku
country: Japan
city: Sumida-Ku
country: Japan
city: Takaoka,Toyama
country: Japan
city: Takasaki
country: Japan
city: Tokorozawa
country: Japan
city: Tokushima
country: Japan
city: Tomishiro
country: Japan
city: Tsu
country: Japan
city: Ureshino
country: Japan
city: Yokohama
country: Japan
city: Busan
country: Korea, Republic of
city: Daegu
country: Korea, Republic of
city: Daejeon
country: Korea, Republic of
city: Gwangju
country: Korea, Republic of
city: Incheon
country: Korea, Republic of
city: Jeonju-Si
country: Korea, Republic of
city: Namdong-Gu
country: Korea, Republic of
city: Seongnam-Si
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Suwon
country: Korea, Republic of
city: Alytus
country: Lithuania
city: Kaunas
country: Lithuania
city: Klaipeda
country: Lithuania
city: Siauliai
country: Lithuania
city: Kuala Lumpur
country: Malaysia
city: Kuching
country: Malaysia
city: Cuernavaca
country: Mexico
city: Guadalajara
country: Mexico
city: Juarez
country: Mexico
city: Merida
country: Mexico
city: Mexicali
country: Mexico
city: Mexico Df
country: Mexico
city: Morelia
country: Mexico
city: México
country: Mexico
city: San Luis De Potosi
country: Mexico
city: Bialystok
country: Poland
city: Bydgoszcz
country: Poland
city: Elblag
country: Poland
city: Lublin
country: Poland
city: Poznan
country: Poland
city: Ustron
country: Poland
city: Warszawa N/A
country: Poland
city: Warszawa
country: Poland
city: Bucharest
country: Romania
city: Bucuresti
country: Romania
city: Cluj-Napoca
country: Romania
city: Iasi
country: Romania
city: Kemerovo
country: Russian Federation
city: Moscow
country: Russian Federation
city: Novosibirsk
country: Russian Federation
city: Orenburg
country: Russian Federation
city: Ryazan
country: Russian Federation
city: Saint Petersburg
country: Russian Federation
city: Saratov
country: Russian Federation
city: Smolensk
country: Russian Federation
city: St Petersburg
country: Russian Federation
city: Ulyanovsk
country: Russian Federation
city: Yaroslavl
country: Russian Federation
city: Belgrade
country: Serbia
city: Kragujevac
country: Serbia
city: Niska Banja
country: Serbia
city: Cape Town
country: South Africa
city: Port Elizabeth
country: South Africa
city: Pretoria
country: South Africa
city: Kaohsiung
country: Taiwan
city: Taichung City
country: Taiwan
city: Taichung
country: Taiwan
city: Taipei
country: Taiwan
city: Donetsk
country: Ukraine
city: Kharkiv
country: Ukraine
city: Kiev
country: Ukraine
city: Kyiv
country: Ukraine
city: Odesa
country: Ukraine
city: Sympheropol
country: Ukraine
city: Vinnytsia
country: Ukraine
city: Zaporizhzhia
country: Ukraine
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References:
citation: Takeuchi T, Thorne C, Karpouzas G, Sheng S, Xu W, Rao R, Fei K, Hsu B, Tak PP. Sirukumab for rheumatoid arthritis: the phase III SIRROUND-D study. Ann Rheum Dis. 2017 Dec;76(12):2001-2008. doi: 10.1136/annrheumdis-2017-211328. Epub 2017 Aug 30.