An Effectiveness and Safety Study of Intravenous Golimumab in Patients With Active Rheumatoid Arthritis Despite Treatment With Methotrexate Therapy

NCT ID: NCT00973479

Last Updated: 2013-12-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 592 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-09-30
• Study Completion Date: 2013-02-28

Brief Summary

The purpose of this study is to evaluate clinical effectiveness and safety of golimumab with methotrexate (MTX) in the treatment of rheumatoid arthritis (RA) when compared to MTX alone.

Detailed Description

This is a randomized (study medication is assigned by chance), double-blind (neither physician nor participants knows the treatment that the participant receives), placebo-controlled (an inactive substance is compared with a medication to test whether the medication has a real effect in a clinical study), multicenter, 2-arm (2 groups) study of golimumab in participants with active RA despite concurrent MTX therapy. Approximately 564 participants will be randomly allocated to 1 of 2 treatment groups in a 2:1 ratio ie, Group 1(approximately 376 participants will receive golimumab + MTX) and Group 2 (approximately 188 participants will receive MTX + placebo). Total duration of study for each participant is 112 weeks. Safety will be evaluated by assessment of adverse events, tuberculosis testing and blood testing.

Conditions

Arthritis, Rheumatoid

Keywords

Arthritis, Rheumatoid; Active rheumatoid arthritis; Golimumab; CNTO148; Anti-TNFalpha monoclonal antibody; Methotrexate; Intravenous

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Group I: Placebo + Methotrexate (MTX)

Participants will receive placebo at Weeks 0, 4, 12, and 16. Participants will cross over to golimumab at Week 24, and receive administrations at Weeks 24, 28, and every 8 weeks thereafter. They will be maintained on their stable dose of commercial methotrexate throughout the study. Participants will be eligible for early escape (receive golimumab) at Week 16 if they demonstrate a less than 10 percent improvement in both tender and swollen joint count. These participants will receive golimumab at Weeks 16, 20, and every 8 weeks thereafter.

Group Type: EXPERIMENTAL

Golimumab

Intervention Type: DRUG

Participants will receive 2 mg/kg of golimumab intravenously over 30 ± 10 minutes. Group 1: at Weeks 0, 4, and every 8 weeks thereafter (up to Week 100). Group II: Weeks 24, 28, and every 8 weeks thereafter (up to Week 100); Early escape: at Week 16, 20 and every 8 weeks thereafter (up to Week 100).

Placebo

Intervention Type: OTHER

Participants will receive placebo intravenous infusion over 30 ± 10 minutes as: Group I: at Week 16 and 24; Group II: at Weeks 0, 4, 12, 16, and 20; and for early escape: at Week 24.

methotrexate (MTX)

Intervention Type: DRUG

Participants will be maintained on their stable dose of commercial MTX (between 15 to 25 mg/week) throughout the study.

Group II: Golimumab + Methotrexate (MTX)

Participants will receive golimumab at Weeks 0, 4, and every 8 weeks thereafter. They will be maintained on their stable dose of commercial methotrexate throughout the study. Participants will receive a placebo infusion at Week 16 and Week 24 to maintain the blind.

Group Type: PLACEBO_COMPARATOR

Golimumab

Intervention Type: DRUG

Participants will receive 2 mg/kg of golimumab intravenously over 30 ± 10 minutes. Group 1: at Weeks 0, 4, and every 8 weeks thereafter (up to Week 100). Group II: Weeks 24, 28, and every 8 weeks thereafter (up to Week 100); Early escape: at Week 16, 20 and every 8 weeks thereafter (up to Week 100).

Placebo

Intervention Type: OTHER

Participants will receive placebo intravenous infusion over 30 ± 10 minutes as: Group I: at Week 16 and 24; Group II: at Weeks 0, 4, 12, 16, and 20; and for early escape: at Week 24.

methotrexate (MTX)

Intervention Type: DRUG

Participants will be maintained on their stable dose of commercial MTX (between 15 to 25 mg/week) throughout the study.

Interventions

Golimumab

Participants will receive 2 mg/kg of golimumab intravenously over 30 ± 10 minutes. Group 1: at Weeks 0, 4, and every 8 weeks thereafter (up to Week 100). Group II: Weeks 24, 28, and every 8 weeks thereafter (up to Week 100); Early escape: at Week 16, 20 and every 8 weeks thereafter (up to Week 100).

Intervention Type: DRUG

Placebo

Participants will receive placebo intravenous infusion over 30 ± 10 minutes as: Group I: at Week 16 and 24; Group II: at Weeks 0, 4, 12, 16, and 20; and for early escape: at Week 24.

Intervention Type: OTHER

methotrexate (MTX)

Participants will be maintained on their stable dose of commercial MTX (between 15 to 25 mg/week) throughout the study.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Diagnosis of rheumatoid arthritis (RA) for at least 3 months prior to screening
• Have been treated with and tolerated methotrexate (MTX) at a dose of at least 15 mg/week for at least 3 months prior to screening, and have been on a stable MTX dose of 15 mg/week to 25 mg/week for at least 4 weeks prior to screening
• Have an active RA, as defined by disease activity with at least 6 swollen and 6 tender joints, at the time of screening and at baseline
• C-Reactive Protein greater than or equal to 1.0 mg/dL at screening
• No history of latent or active tuberculosis prior to screening

Exclusion Criteria

• Other inflammatory diseases, including but not limited to psoriatic arthritis, ankylosing spondylitis, systemic lupus erythematosus, or lyme disease
• Treated with disease modifying agents (other than methotrexate)/systemic immunosuppressives (eg, D-penicillamine, hydroxychloroquine, chloroquine, oral or parenteral gold, sulfasalazine, leflunomide, azathioprine, cyclosporine, mycophenolate mofetil) during the 4 weeks prior to first administration of study agent
• Received intra-articular (in the joint), intramuscular (in the muscle), or intravenous corticosteroids, including adrenocorticotropic hormone, during the 4 weeks prior to first administration of study agent
• Known allergy to human immunoglobulin proteins or other components of golimumab
• Received any commercial or investigational anti-tumor necrosis factor alpha therapy such as but not exclusively infliximab, golimumab, adalimumab or etanercept

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Schering-Plough

INDUSTRY

Sponsor Role: collaborator

Centocor, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Centocor, Inc. Clinical Trial

Role: STUDY_DIRECTOR

Centocor, Inc.

Locations

Daytona Beach, Florida, United States

Miami, Florida, United States

Palm Harbor, Florida, United States

Moline, Illinois, United States

Wheaton, Maryland, United States

Worcester, Massachusetts, United States

Lincoln, Nebraska, United States

Cincinnati, Ohio, United States

Lubbock, Texas, United States

Buenos Aires, , Argentina

Córdoba, , Argentina

Rosario, , Argentina

San Juan, , Argentina

San Miguel de Tucumán, , Argentina

Santa Fe, , Argentina

Cairns, , Australia

Maroochydore, , Australia

Melbourne, , Australia

Woodville, , Australia

Woolloongabba, , Australia

Antioquia, , Colombia

Barranquilla, , Colombia

Bogotá, , Colombia

Cali Valley Del Cauca, , Colombia

Medellín, , Colombia

Budapest, , Hungary

Debrecen, , Hungary

Eger, , Hungary

Győr, , Hungary

Gyula, , Hungary

Szombathely, , Hungary

Veszprém, , Hungary

Alytus, , Lithuania

Kaunas, , Lithuania

Klaipėda, , Lithuania

Šiauliai, , Lithuania

Vilnius, , Lithuania

George Town, , Malaysia

Ipoh, , Malaysia

Johor Bahru, , Malaysia

Kota Kinabalu, , Malaysia

Kuantan, , Malaysia

Kuching, , Malaysia

Precinct 7, , Malaysia

Selangor Darul Ehasan, , Malaysia

Seremban, , Malaysia

Guadalajara, , Mexico

León, , Mexico

Mexico City, , Mexico

México, , Mexico

Monterrey, , Mexico

Auckland, , New Zealand

Takapuna Auckland, , New Zealand

Timaru, , New Zealand

Bialystok, , Poland

Bydgoszcz, , Poland

Działdowo, , Poland

Elblag, , Poland

Katowice, , Poland

Lublin, , Poland

Poznan, , Poland

Sopot, , Poland

Szczecin, , Poland

Warsaw, , Poland

Wroclaw, , Poland

Włoszczowa, , Poland

Chelyabinsk, , Russia

Krasnoyarsk, , Russia

Moscow, , Russia

Petrozavodsk, , Russia

Saint Petersburg, , Russia

Saratov, , Russia

Yekaterinburg, , Russia

Anyang, , South Korea

Daegu, , South Korea

Daejeon, , South Korea

Incheon, , South Korea

Pusan, , South Korea

Seoul, , South Korea

Donetsk, , Ukraine

Ivano-Frankivsk, , Ukraine

Kharkiv, , Ukraine

Kyiv, , Ukraine

Odesa, , Ukraine

Simferopol, , Ukraine

Ternopil, , Ukraine

Vinnitsa, , Ukraine

Zaporizhzhya, , Ukraine

Countries

United States; Argentina; Australia; Colombia; Hungary; Lithuania; Malaysia; Mexico; New Zealand; Poland; Russia; South Korea; Ukraine

References

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Reference Type: DERIVED

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Lee JB, Broadwell A, Fan Y, Hu C, Adedokun OJ, Chakravarty SD, Zhou H, Xu Z, Leu JH. Population Pharmacokinetic and Exposure-Response Model Simulations: Predicted Exposure and Efficacy for Maintenance Doses of Intravenous Golimumab Every 6 or 8 Weeks in Patients With Moderately to Severely Active Rheumatoid Arthritis. Clin Ther. 2022 Mar;44(3):457-464.e2. doi: 10.1016/j.clinthera.2022.01.015. Epub 2022 Feb 17.

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Tesser J, Kafka S, DeHoratius RJ, Xu S, Hsia EC, Turkiewicz A. Efficacy and safety of intravenous golimumab plus methotrexate in patients with rheumatoid arthritis aged < 65 years and those >/= 65 years of age. Arthritis Res Ther. 2019 Aug 20;21(1):190. doi: 10.1186/s13075-019-1968-x.

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Bingham CO 3rd, Mendelsohn AM, Kim L, Xu Z, Leu J, Han C, Lo KH, Westhovens R, Weinblatt ME; GO-FURTHER Investigators. Maintenance of Clinical and Radiographic Benefit With Intravenous Golimumab Therapy in Patients With Active Rheumatoid Arthritis Despite Methotrexate Therapy: Week-112 Efficacy and Safety Results of the Open-Label Long-Term Extension of a Phase III, Double-Blind, Randomized, Placebo-Controlled Trial. Arthritis Care Res (Hoboken). 2015 Dec;67(12):1627-36. doi: 10.1002/acr.22556.

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Bingham CO 3rd, Weinblatt M, Han C, Gathany TA, Kim L, Lo KH, Baker D, Mendelsohn A, Westhovens R. The effect of intravenous golimumab on health-related quality of life in rheumatoid arthritis: 24-week results of the phase III GO-FURTHER trial. J Rheumatol. 2014 Jun;41(6):1067-76. doi: 10.3899/jrheum.130864. Epub 2014 May 1.

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Other Identifiers

CNTO148ART3001

Identifier Type: OTHER

Identifier Source: secondary_id

2008-006064-11

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CR015784

Identifier Type: -

Identifier Source: org_study_id