A Study Comparing Sirukumab (CNTO 136) Monotherapy With Adalimumab (HUMIRA®) Monotherapy in the Treatment of Active Rheumatoid Arthritis (SIRROUND-H)

A Multicenter, Randomized, Double-blind, Parallel Group Study of Sirukumab Monotherapy Compared With HUMIRA® Monotherapy Administered Subcutaneously, in Subjects With Active Rheumatoid Arthritis

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.

Study Overview

• Status: Completed
• Conditions: Arthritis, Rheumatoid
• Intervention / Treatment: Drug: Placebo; Biological: adalimumab 40 mg; Biological: sirukumab 100 mg; Biological: sirukumab 50 mg

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.

• Study Type: Interventional
• Enrollment (Actual): 559
• Phase: Phase 3

Contacts and Locations

Study Locations

• Bulgaria
  • Ruse, Bulgaria
  • Sofia, Bulgaria
• Chile
  • Puerto Montt, Chile
  • Temuco, Chile
• Colombia
  • Barranquilla, Colombia
  • Bogota, Colombia
  • Bucaramanga, Colombia
• Germany
  • Bad Doberan, Germany
  • Berlin, Germany
  • Köln, Germany
  • Ratingen, Germany
  • Vogelsang-Gommern, Germany
• Hungary
  • Debrecen, Hungary
  • Gödöllő, Hungary
• Lithuania
  • Klaipeda, Lithuania
  • Siauliai, Lithuania
  • Vilnius, Lithuania
• Mexico
  • Chihuahua, Mexico
  • Guadalajara, Mexico
  • Jalisco, Mexico
  • Mexicali, Mexico
• Moldova, Republic of
  • Chisinau, Moldova, Republic of
• Poland
  • Bydgoszcz, Poland
  • Bytom, Poland
  • Krakow, Poland
  • Lublin, Poland
  • Nadarzyn, Poland
  • Poznan, Poland
  • Warszawa, Poland
  • Wroclaw, Poland
• Romania
  • Bucharest, Romania
  • Constanta, Romania
  • Ploiesti, Romania
• Russian Federation
  • Arkhangelsk, Russian Federation
  • Kazan, Russian Federation
  • Kemerovo, Russian Federation
  • Kursk, Russian Federation
  • Moscow, Russian Federation
  • Novosibirsk, Russian Federation
  • Petrozavodsk, Russian Federation
  • Ryazan, Russian Federation
  • Saint Petersburg, Russian Federation
  • St Petersburg, Russian Federation
  • St-Petersburg, Russian Federation
  • Tomsk, Russian Federation
  • Tver, Russian Federation
  • Vladimir, Russian Federation
  • Yaroslavl, Russian Federation
• Serbia
  • Belgrade, Serbia
  • Novi Sad, Serbia
  • Zemun, Serbia
• South Africa
  • Cape Town, South Africa
  • Durban, South Africa
  • Kempton Park, South Africa
  • Stellenbosch, South Africa
• Spain
  • Coruna, Spain
  • Madrid, Spain
• Ukraine
  • Chernihiv, Ukraine
  • Kryvyi Rih, Ukraine
  • Kyiv, Ukraine
  • Lviv, Ukraine
  • Odessa, Ukraine
  • Poltava, Ukraine
  • Sumy, Ukraine
  • Ternopil, Ukraine
  • Vinnytsia, Ukraine
  • Zaporizhzhia, Ukraine
• United States
  • Alabama
    • Birmingham, Alabama, United States
  • Arizona
    • Phoenix, Arizona, United States
  • California
    • Arvin, California, United States
    • El Cajon, California, United States
    • Huntington Beach, California, United States
    • Pleasanton, California, United States
    • Thousand Oaks, California, United States
    • Tustin, California, United States
    • Whittier, California, United States
  • Delaware
    • Newark, Delaware, United States
  • Florida
    • Aventura, Florida, United States
    • Dunedin, Florida, United States
    • Miami, Florida, United States
    • New Port Richey, Florida, United States
    • Palm Harbor, Florida, United States
    • Plantation, Florida, United States
    • Tampa, Florida, United States
  • Kansas
    • Kansas City, Kansas, United States
  • Kentucky
    • Elizabethtown, Kentucky, United States
    • Paducah, Kentucky, United States
  • Maryland
    • Frederick, Maryland, United States
    • Wheaton, Maryland, United States
  • Missouri
    • Saint Louis, Missouri, United States
  • Nevada
    • Las Vegas, Nevada, United States
  • North Carolina
    • Salisbury, North Carolina, United States
    • Wilmington, North Carolina, United States
  • Ohio
    • Dayton, Ohio, United States
  • Oregon
    • Portland, Oregon, United States
  • Pennsylvania
    • Duncansville, Pennsylvania, United States
    • Wexford, Pennsylvania, United States
    • Wyomissing, Pennsylvania, United States
  • Tennessee
    • Jackson, Tennessee, United States
    • Nashville, Tennessee, United States
  • Texas
    • Austin, Texas, United States
    • Carrollton, Texas, United States
    • Corpus Christi, Texas, United States
    • Cypress, Texas, United States
    • Lubbock, Texas, United States
    • McKinney, Texas, United States
    • Mesquite, Texas, United States
  • Virginia
    • Chesapeake, Virginia, United States
  • West Virginia
    • Clarksburg, West Virginia, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1 (adalimumab 40 mg); 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.	Biological: adalimumab 40 mg; SC injections; Other Names: HUMIRA®
Experimental: Group 2 (sirukumab 100 mg); 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).	Drug: Placebo; SC injections; Biological: sirukumab 100 mg; SC injections; Other Names: CNTO 136
Experimental: Group 3 (sirukumab 50 mg); 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).	Drug: Placebo; SC injections; Biological: sirukumab 50 mg; SC injections; Other Names: CNTO 136

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	Baseline and Week 24
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).	Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Week 24
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.	Week 24

Collaborators and Investigators

• Sponsor: Janssen Research & Development, LLC
• Collaborators: GlaxoSmithKline

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): April 4, 2014
• Primary Completion (Actual): August 17, 2016
• Study Completion (Actual): August 17, 2016

Study Registration Dates

• First Submitted: December 18, 2013
• First Submitted That Met QC Criteria: December 18, 2013
• First Posted (Estimate): December 24, 2013

Study Record Updates

• Last Update Posted (Actual): October 26, 2017
• Last Update Submitted That Met QC Criteria: September 25, 2017
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Keywords: Rheumatoid arthritis; Adalimumab; CNTO 136; Sirukumab; HUMIRA®
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid; Physiological Effects of Drugs; Anti-Inflammatory Agents; Antirheumatic Agents; Immunologic Factors; Adalimumab; Antibodies, Monoclonal
• Other Study ID Numbers: CR103111; CNTO136ARA3005 (Other Identifier: Janssen Research & Development, LLC); 2013-001417-32 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated device product: No