Back to resultsA Study Comparing Sirukumab (CNTO 136) Monotherapy With Adalimumab (HUMIRA®) Monotherapy in the Treatment of Active Rheumatoid Arthritis (SIRROUND-H)
Primary Purpose
Arthritis, Rheumatoid
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
adalimumab 40 mg
sirukumab 100 mg
sirukumab 50 mg
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Arthritis, Rheumatoid focused on measuring Rheumatoid arthritis, CNTO 136, Sirukumab, Adalimumab, HUMIRA®
Eligibility Criteria
Inclusion Criteria:
- Have a diagnosis of rheumatoid arthritis (RA) for at least 6 months before screening
- Have moderately to severely active RA with at least 8 of 68 tender joints and 6 of 66 swollen joints, at screening and at baseline
- Have previous or current treatment with methotrexate (MTX) and are considered intolerant to MTX, and/or are considered inappropriate for treatment with MTX, (including MTX-naïve subjects for whom it is inappropriate to administer MTX) and/or an inadequate responder to methotrexate
- Must not have received MTX or any other non-biologic DMARD including but not limited to sulfasalazine, hydroxychloroquine, chloroquine, and bucillamine for at least 2 weeks prior to the first administration of the study agent
- C-reactive protein >= 10.00 mg/L or erythrocyte sedimentation rate >=28 mm/hr at screening
Exclusion Criteria:
- Has Functional Class IV as defined by the ACR Classification of Functional Status in Rheumatoid Arthritis
- Has ever received biologic therapy for RA, including but not limited to the following: TNF-alpha inhibitors, tocilizumab, rituximab, anakinra, abatacept
- Has ever used tofacitinib therapy or any other JAK inhibitor
- Has received intra-articular, intramuscular, 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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
Group 1 (adalimumab 40 mg)
Group 2 (sirukumab 100 mg)
Group 3 (sirukumab 50 mg)
Arm Description
Adalimumab 40 mg SC at Weeks 0, 2, and every 2 weeks through Week 52. At Week 16, subjects who have < 20% improvement from baseline in both swollen and tender joint counts will early escape in a blinded fashion and receive adalimumab 40 mg every week through Week 52.
Sirukumab 100 mg SC at Weeks 0, 2, and every 2 weeks through Week 52. Subjects may meet the early escape criteria at Week 16 (< 20% improvement from baseline in both swollen and tender joint counts) but no sirukumab dose adjustments will made for these subjects. However, these subjects will receive placebo injections every 2 weeks between the sirukumab injections (ie, subjects that early escape will receive a weekly injection of alternating sirukumab and placebo, to preserve the blind).
Sirukumab 50 mg SC at Weeks 0, 4, and every 4 weeks through Week 52. Between sirukumab injections, placebo SC injections will be administered at Weeks 2, 6, and every 4 weeks through Week 50. At Week 16, subjects who have < 20% improvement from baseline in both swollen and tender joint counts will early escape in a blinded fashion and receive sirukumab 100 mg every 2 weeks through Week 52 and placebo injections every 2 weeks between the sirukumab injections (ie, subjects that early escape will receive a weekly injection of alternating sirukumab and placebo, to preserve the blind).
Outcomes
Primary Outcome Measures
Change From Baseline in Disease Activity Index Score 28 (DAS28) Erythrocyte Sedimentation Rate (ESR) at Week 24
The Disease Activity Index Score 28 using ESR [DAS28 (ESR)] is a derived score combining tender joints (28 joints), swollen joints (28 joints), ESR, and Patient's Global Assessment of Disease Activity. The 28 joints evaluated for swelling and tenderness were shoulder, elbow, wrist, MCP1, MCP2, MCP3, MCP4, MCP5, PIP1, PIP2, PIP3, PIP4, PIP5 joints of the upper right and upper left extremities as well as the knee joints of the lower right and lower left extremities. The DAS28-ESR is expressed on a score range of "0-10", with the minimum score= 0 (best) to maximum score= 10 (worst).
Percentage of Participants With an American College of Rheumatology (ACR) 50 Response at Week 24
The ACR 50 Response is defined as greater than or equal to (>=) 50 percent (%) improvement in swollen joint count (66 joints) and tender joint count (68 joints) and >= 50% improvement in 3 of following 5 assessments: subject's assessment of pain using Visual Analog Scale (VAS) (0-10 millimeter [mm], 0 mm=no pain and 10 mm=worst possible pain), subject's global assessment of disease activity by using VAS (the scale ranges from 0 mm to 100 mm, [0 mm=no pain to 100 mm=worst possible pain]), physician's global assessment of disease activity using VAS (the scale ranges from 0 to 10, [0=no arthritis activity to 10=extremely active arthritis]), participant's assessment of physical function measured by Health Assessment Questionnaire-Disability Index (HAQ-DI) (the scale ranges from 0, indicating no difficulty, to 3, indicating inability to perform a task in that area) and serum C-Reactive Protein (CRP).
Secondary Outcome Measures
Percentage of Participants With Disease Activity Index Score 28 (DAS28) Using Erythrocyte Sedimentation Rate (ESR) Remission at Week 24
The Disease Activity Index Score 28 using ESR [DAS28 (ESR)] is a derived score combining tender joints (28 joints), swollen joints (28 joints), ESR, and Patient's Global Assessment of Disease Activity. The 28 joints evaluated for swelling and tenderness were shoulder, elbow, wrist, MCP1, MCP2, MCP3, MCP4, MCP5, PIP1, PIP2, PIP3, PIP4, PIP5 joints of the upper right and upper left extremities as well as the knee joints of the lower right and lower left extremities. The DAS28-ESR is expressed on a score range of "0-10", with the minimum score= 0 (best) to maximum score= 10 (worst). The DAS28 (ESR) remission is defined as a DAS28 (ESR) value of less than 2.6 at a visit.
Percentage of Participants With an American College of Rheumatology (ACR) 20 Response at Week 24
The ACR 20 Response is defined as >= 20% improvement in swollen joint count (66 joints) and tender joint count (68 joints) and >=20% improvement in 3 of following 5 assessments: subject's assessment of pain using VAS (0-10 mm, 0 mm=no pain and 10 mm=worst possible pain), subject's global assessment of disease activity by using VAS (the scale ranges from 0 mm to 100 mm, [0 mm=no pain to 100 mm=worst possible pain]), physician's global assessment of disease activity using VAS, subject'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 CRP.
Full Information
NCT ID
NCT02019472
First Posted
December 18, 2013
Last Updated
September 25, 2017
Sponsor
Janssen Research & Development, LLC
Collaborators
GlaxoSmithKline
1. Study Identification
Unique Protocol Identification Number
NCT02019472
Brief Title
A Study Comparing Sirukumab (CNTO 136) Monotherapy With Adalimumab (HUMIRA®) Monotherapy in the Treatment of Active Rheumatoid Arthritis
Acronym
SIRROUND-H
Official Title
A Multicenter, Randomized, Double-blind, Parallel Group Study of Sirukumab Monotherapy Compared With HUMIRA® Monotherapy Administered Subcutaneously, in Subjects With Active Rheumatoid Arthritis
Study Type
Interventional
2. Study Status
Record Verification Date
September 2017
Overall Recruitment Status
Completed
Study Start Date
April 4, 2014 (Actual)
Primary Completion Date
August 17, 2016 (Actual)
Study Completion Date
August 17, 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Janssen Research & Development, LLC
Collaborators
GlaxoSmithKline
4. Oversight
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The primary objective is to investigate the efficacy of sirukumab monotherapy compared with adalimumab monotherapy in biologic naïve subjects with active rheumatoid arthritis who are intolerant to methotrexate, who are considered inappropriate for treatment with methotrexate or who are inadequate responders to methotrexate.
Detailed Description
This is a randomized, double-blind, parallel-group, global, multicenter study of subcutaneous (SC) sirukumab monotherapy compared with adalimumab monotherapy in subjects with active rheumatoid arthritis. Approximately 510 subjects will be randomly assigned in a 1:1:1 ratio to receive treatment with adalimumab 40 mg SC every 2 weeks, sirukumab 100 mg SC every 2 weeks, or 50 mg SC every 4 weeks, with approximately 170 subjects per treatment group. At Week 16, subjects in all treatment groups who have < 20% improvement from baseline in both swollen and tender joint counts will qualify for early escape. The expected duration of the study is 68 weeks. This includes 52 weeks of treatment with study agent and 16 weeks of safety follow-up after the last study agent administration. The study will end when the last subject completes the last scheduled visit (Week 68 visit or completes the 16 week safety follow-up, whichever is later). Subject safety will be monitored through the end of the study.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Arthritis, Rheumatoid
Keywords
Rheumatoid arthritis, CNTO 136, Sirukumab, Adalimumab, HUMIRA®
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
559 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Group 1 (adalimumab 40 mg)
Arm Type
Experimental
Arm Description
Adalimumab 40 mg SC at Weeks 0, 2, and every 2 weeks through Week 52. At Week 16, subjects who have < 20% improvement from baseline in both swollen and tender joint counts will early escape in a blinded fashion and receive adalimumab 40 mg every week through Week 52.
Arm Title
Group 2 (sirukumab 100 mg)
Arm Type
Experimental
Arm Description
Sirukumab 100 mg SC at Weeks 0, 2, and every 2 weeks through Week 52. Subjects may meet the early escape criteria at Week 16 (< 20% improvement from baseline in both swollen and tender joint counts) but no sirukumab dose adjustments will made for these subjects. However, these subjects will receive placebo injections every 2 weeks between the sirukumab injections (ie, subjects that early escape will receive a weekly injection of alternating sirukumab and placebo, to preserve the blind).
Arm Title
Group 3 (sirukumab 50 mg)
Arm Type
Experimental
Arm Description
Sirukumab 50 mg SC at Weeks 0, 4, and every 4 weeks through Week 52. Between sirukumab injections, placebo SC injections will be administered at Weeks 2, 6, and every 4 weeks through Week 50. At Week 16, subjects who have < 20% improvement from baseline in both swollen and tender joint counts will early escape in a blinded fashion and receive sirukumab 100 mg every 2 weeks through Week 52 and placebo injections every 2 weeks between the sirukumab injections (ie, subjects that early escape will receive a weekly injection of alternating sirukumab and placebo, to preserve the blind).
Intervention Type
Biological
Intervention Name(s)
adalimumab 40 mg
Other Intervention Name(s)
HUMIRA®
Intervention Description
SC injections
Intervention Type
Biological
Intervention Name(s)
sirukumab 100 mg
Other Intervention Name(s)
CNTO 136
Intervention Description
SC injections
Intervention Type
Biological
Intervention Name(s)
sirukumab 50 mg
Other Intervention Name(s)
CNTO 136
Intervention Description
SC injections
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
SC injections
Primary Outcome Measure Information:
Title
Change From Baseline in Disease Activity Index Score 28 (DAS28) Erythrocyte Sedimentation Rate (ESR) at Week 24
Description
The Disease Activity Index Score 28 using ESR [DAS28 (ESR)] is a derived score combining tender joints (28 joints), swollen joints (28 joints), ESR, and Patient's Global Assessment of Disease Activity. The 28 joints evaluated for swelling and tenderness were shoulder, elbow, wrist, MCP1, MCP2, MCP3, MCP4, MCP5, PIP1, PIP2, PIP3, PIP4, PIP5 joints of the upper right and upper left extremities as well as the knee joints of the lower right and lower left extremities. The DAS28-ESR is expressed on a score range of "0-10", with the minimum score= 0 (best) to maximum score= 10 (worst).
Time Frame
Baseline and Week 24
Title
Percentage of Participants With an American College of Rheumatology (ACR) 50 Response at Week 24
Description
The ACR 50 Response is defined as greater than or equal to (>=) 50 percent (%) improvement in swollen joint count (66 joints) and tender joint count (68 joints) and >= 50% improvement in 3 of following 5 assessments: subject's assessment of pain using Visual Analog Scale (VAS) (0-10 millimeter [mm], 0 mm=no pain and 10 mm=worst possible pain), subject's global assessment of disease activity by using VAS (the scale ranges from 0 mm to 100 mm, [0 mm=no pain to 100 mm=worst possible pain]), physician's global assessment of disease activity using VAS (the scale ranges from 0 to 10, [0=no arthritis activity to 10=extremely active arthritis]), participant's assessment of physical function measured by Health Assessment Questionnaire-Disability Index (HAQ-DI) (the scale ranges from 0, indicating no difficulty, to 3, indicating inability to perform a task in that area) and serum C-Reactive Protein (CRP).
Time Frame
Week 24
Secondary Outcome Measure Information:
Title
Percentage of Participants With Disease Activity Index Score 28 (DAS28) Using Erythrocyte Sedimentation Rate (ESR) Remission at Week 24
Description
The Disease Activity Index Score 28 using ESR [DAS28 (ESR)] is a derived score combining tender joints (28 joints), swollen joints (28 joints), ESR, and Patient's Global Assessment of Disease Activity. The 28 joints evaluated for swelling and tenderness were shoulder, elbow, wrist, MCP1, MCP2, MCP3, MCP4, MCP5, PIP1, PIP2, PIP3, PIP4, PIP5 joints of the upper right and upper left extremities as well as the knee joints of the lower right and lower left extremities. The DAS28-ESR is expressed on a score range of "0-10", with the minimum score= 0 (best) to maximum score= 10 (worst). The DAS28 (ESR) remission is defined as a DAS28 (ESR) value of less than 2.6 at a visit.
Time Frame
Week 24
Title
Percentage of Participants With an American College of Rheumatology (ACR) 20 Response at Week 24
Description
The ACR 20 Response is defined as >= 20% improvement in swollen joint count (66 joints) and tender joint count (68 joints) and >=20% improvement in 3 of following 5 assessments: subject's assessment of pain using VAS (0-10 mm, 0 mm=no pain and 10 mm=worst possible pain), subject's global assessment of disease activity by using VAS (the scale ranges from 0 mm to 100 mm, [0 mm=no pain to 100 mm=worst possible pain]), physician's global assessment of disease activity using VAS, subject'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 CRP.
Time Frame
Week 24
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Have a diagnosis of rheumatoid arthritis (RA) for at least 6 months before screening
Have moderately to severely active RA with at least 8 of 68 tender joints and 6 of 66 swollen joints, at screening and at baseline
Have previous or current treatment with methotrexate (MTX) and are considered intolerant to MTX, and/or are considered inappropriate for treatment with MTX, (including MTX-naïve subjects for whom it is inappropriate to administer MTX) and/or an inadequate responder to methotrexate
Must not have received MTX or any other non-biologic DMARD including but not limited to sulfasalazine, hydroxychloroquine, chloroquine, and bucillamine for at least 2 weeks prior to the first administration of the study agent
C-reactive protein >= 10.00 mg/L or erythrocyte sedimentation rate >=28 mm/hr at screening
Exclusion Criteria:
Has Functional Class IV as defined by the ACR Classification of Functional Status in Rheumatoid Arthritis
Has ever received biologic therapy for RA, including but not limited to the following: TNF-alpha inhibitors, tocilizumab, rituximab, anakinra, abatacept
Has ever used tofacitinib therapy or any other JAK inhibitor
Has received intra-articular, intramuscular, 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Janssen Research & Development, LLC Clinical Trial
Organizational Affiliation
Janssen Research & Development, LLC
Official's Role
Study Director
Facility Information:
City
Birmingham
State/Province
Alabama
Country
United States
City
Phoenix
State/Province
Arizona
Country
United States
City
Arvin
State/Province
California
Country
United States
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El Cajon
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California
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United States
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Huntington Beach
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California
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United States
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Pleasanton
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California
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United States
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Thousand Oaks
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California
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United States
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Tustin
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United States
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Whittier
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United States
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Newark
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Delaware
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United States
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Aventura
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United States
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Dunedin
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Florida
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United States
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Miami
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Florida
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United States
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New Port Richey
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Florida
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United States
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Palm Harbor
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Florida
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United States
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Plantation
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Florida
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United States
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Tampa
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Florida
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United States
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Kansas City
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Kansas
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United States
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Elizabethtown
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Kentucky
Country
United States
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Paducah
State/Province
Kentucky
Country
United States
City
Frederick
State/Province
Maryland
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United States
City
Wheaton
State/Province
Maryland
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United States
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Saint Louis
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Missouri
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United States
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Las Vegas
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Nevada
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United States
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Salisbury
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North Carolina
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United States
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Wilmington
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North Carolina
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United States
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Dayton
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Ohio
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United States
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Portland
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Oregon
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United States
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Duncansville
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Pennsylvania
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United States
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Wexford
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Pennsylvania
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United States
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Wyomissing
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Pennsylvania
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United States
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Jackson
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Tennessee
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United States
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Nashville
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Tennessee
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Austin
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Texas
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United States
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Carrollton
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United States
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Corpus Christi
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Texas
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United States
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Cypress
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Texas
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United States
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Lubbock
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Texas
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United States
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McKinney
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Texas
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United States
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Mesquite
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Texas
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United States
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Chesapeake
State/Province
Virginia
Country
United States
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Clarksburg
State/Province
West Virginia
Country
United States
City
Ruse
Country
Bulgaria
City
Sofia
Country
Bulgaria
City
Puerto Montt
Country
Chile
City
Temuco
Country
Chile
City
Barranquilla
Country
Colombia
City
Bogota
Country
Colombia
City
Bucaramanga
Country
Colombia
City
Bad Doberan
Country
Germany
City
Berlin
Country
Germany
City
Köln
Country
Germany
City
Ratingen
Country
Germany
City
Vogelsang-Gommern
Country
Germany
City
Debrecen
Country
Hungary
City
Gödöllő
Country
Hungary
City
Klaipeda
Country
Lithuania
City
Siauliai
Country
Lithuania
City
Vilnius
Country
Lithuania
City
Chihuahua
Country
Mexico
City
Guadalajara
Country
Mexico
City
Jalisco
Country
Mexico
City
Mexicali
Country
Mexico
City
Chisinau
Country
Moldova, Republic of
City
Bydgoszcz
Country
Poland
City
Bytom
Country
Poland
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Krakow
Country
Poland
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Lublin
Country
Poland
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Nadarzyn
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Poland
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Poznan
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Poland
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Warszawa
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Poland
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Wroclaw
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Poland
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Bucharest
Country
Romania
City
Constanta
Country
Romania
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Ploiesti
Country
Romania
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Arkhangelsk
Country
Russian Federation
City
Kazan
Country
Russian Federation
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Kemerovo
Country
Russian Federation
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Kursk
Country
Russian Federation
City
Moscow
Country
Russian Federation
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Novosibirsk
Country
Russian Federation
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Petrozavodsk
Country
Russian Federation
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Ryazan
Country
Russian Federation
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Saint Petersburg
Country
Russian Federation
City
St Petersburg
Country
Russian Federation
City
St-Petersburg
Country
Russian Federation
City
Tomsk
Country
Russian Federation
City
Tver
Country
Russian Federation
City
Vladimir
Country
Russian Federation
City
Yaroslavl
Country
Russian Federation
City
Belgrade
Country
Serbia
City
Novi Sad
Country
Serbia
City
Zemun
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Serbia
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Cape Town
Country
South Africa
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Durban
Country
South Africa
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Kempton Park
Country
South Africa
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Stellenbosch
Country
South Africa
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Coruna
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Spain
City
Madrid
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Spain
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Chernihiv
Country
Ukraine
City
Kryvyi Rih
Country
Ukraine
City
Kyiv
Country
Ukraine
City
Lviv
Country
Ukraine
City
Odessa
Country
Ukraine
City
Poltava
Country
Ukraine
City
Sumy
Country
Ukraine
City
Ternopil
Country
Ukraine
City
Vinnytsia
Country
Ukraine
City
Zaporizhzhia
Country
Ukraine
12. IPD Sharing Statement
Citations:
PubMed Identifier
29483080
Citation
Taylor PC, Schiff MH, Wang Q, Jiang Y, Zhuang Y, Kurrasch R, Daga S, Rao R, Tak PP, Hsu B. Efficacy and safety of monotherapy with sirukumab compared with adalimumab monotherapy in biologic-naive patients with active rheumatoid arthritis (SIRROUND-H): a randomised, double-blind, parallel-group, multinational, 52-week, phase 3 study. Ann Rheum Dis. 2018 May;77(5):658-666. doi: 10.1136/annrheumdis-2017-212496. Epub 2018 Feb 26.
Results Reference
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A Study Comparing Sirukumab (CNTO 136) Monotherapy With Adalimumab (HUMIRA®) Monotherapy in the Treatment of Active Rheumatoid Arthritis
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