An Efficacy and Safety Study of Golimumab in Patients With Active Rheumatoid Arthritis Despite Methotrexate Therapy

NCT ID: NCT00264550

Last Updated: 2014-04-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 444 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-12-31
• Study Completion Date: 2012-05-31

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of golimumab, alone or in combination with methotrexate (MTX), as compared to methotrexate alone in rheumatoid arthritis (RA) patients who have active rheumatoid arthritis despite treatment with MTX.

Detailed Description

This is a randomized (treatment is assigned by chance), double-blind (neither the physician nor the patient is aware of the received treatment), placebo-controlled study of multiple subcutaneous (SC) administrations of golimumab at 2 doses as monotherapy or in combination with MTX in patients with active RA despite treatment with MTX. The duration of participation in the study for an individual patient will be upto 268 weeks. The patients will be randomly assigned in a 3:3:2:2 ratio to receive golimumab 50 mg or 100 mg or placebo injections under the skin every 4 weeks through week 20 and methotrexate or placebo capsules will be given in addition. At Week 24, all subjects will receive golimumab 50mg or 100mg injections, and golimumab continues for all groups for about 4 and a half more years. At Week 16 any patient in the study who meets criteria for < 20% improvement from baseline in both swollen and tender joint count will enter early escape in a double-blinded fashion. Treatment during the long-term extension will start at Week 52 and continue every 4 weeks thereafter for a total of approximately 5 years from the initial (Week 0) administration of study agent. Patients will return for scheduled follow-up visits generally every 12 weeks for a total length of follow-up of approximately 5 years from the first administration of the study drug.

Conditions

Rheumatoid Arthritis

Study Design

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

Study Groups

Group 1: Placebo + Methotrexate

Placebo subcutaneous (SC) injections every 4 weeks from Week 0 to Week 20 (early escape at Week 16); Methotrexate - 15 to 25mg weekly from Week 0 up to 5 yrs; Golimumab - if early escape, 50mg SC injections every 4 weeks from Week 16 up to 5 years; Golimumab - 50 mg SC injections every 4 weeks from Week 24 up to 5 yrs (unless early escape); Methotrexate - Dr's discretion, weekly dose adjusted after unblinding; Golimumab - Dr's discretion after unblinding, dose adjusted from 50 to 100mg and from 100 to 50mg. Duration of the blinded period will be until the week-52 database lock.

Group Type: PLACEBO_COMPARATOR

Methotrexate

Intervention Type: DRUG

Participants will receive methotrexate capsules weekly.

Placebo injection

Intervention Type: DRUG

Participants will receive subcutaneous (SC) injections of placebo every 4 weeks.

Group 2: Golimumab 100 mg + Placebo

Golimumab 100 mg SC injections every 4 weeks from Week 0 up to 5 yrs; Placebo - 7-10 capsules weekly during blinded period (or Week 16 if early escape); Methotrexate - if early escape, 15 to 25mg weekly from Week 16 up to 5 yrs; Methotrexate - Dr's discretion, weekly dose adjusted after unblinding; Golimumab - Dr's discretion after unblinding, dose adjusted from 100 to 50mg. Duration of the blinded period will be until the week-52 database lock.

Group Type: EXPERIMENTAL

Golimumab 100 mg

Intervention Type: DRUG

Participants will receive subcutaneous (SC) injections of golimumab 100 mg every 4 weeks.

Placebo capsules

Intervention Type: DRUG

Participants will receive placebo capsules weekly

Group 3: Golimumab 50 mg + Methotrexate

Golimumab 50 mg SC injections every 4 weeks from Week 0 up to 5 yrs (unless early escape at Week 16); Methotrexate - 15 to 25 mg weekly from Week 0 up to 5 years; Golimumab - if early escape, 100 mg SC injections every 4 weeks from Week 16 up to 5 yrs; Methotrexate - Dr's discretion, weekly dose adjusted after unblinding; Golimumab - Dr's discretion after unblinding, dose adjusted from 50 to100mg and from 100 to 50mg. Duration of the blinded period will be until the week-52 database lock.

Group Type: EXPERIMENTAL

Golimumab 50 mg

Intervention Type: DRUG

Participants will receive subcutaneous (SC) injections of golimumab 50 mg every 4 weeks.

Methotrexate

Intervention Type: DRUG

Participants will receive methotrexate capsules weekly.

Group 4: Golimumab 100 mg + Methotrexate

Golimumab100 mg SC injections every 4 weeks from Week 0 up to 5 yrs; Methotrexate - 15 to 25 mg weekly from Week 0 up to 5 yrs; Methotrexate - Dr's discretion, weekly dose adjusted after unblinding; Golimumab - Dr's discretion after unblinding, dose adjusted from 100 to 50mg. Duration of the blinded period will be until the week-52 database lock.

Group Type: EXPERIMENTAL

Golimumab 100 mg

Intervention Type: DRUG

Participants will receive subcutaneous (SC) injections of golimumab 100 mg every 4 weeks.

Methotrexate

Intervention Type: DRUG

Participants will receive methotrexate capsules weekly.

Interventions

Golimumab 100 mg

Participants will receive subcutaneous (SC) injections of golimumab 100 mg every 4 weeks.

Intervention Type: DRUG

Golimumab 50 mg

Participants will receive subcutaneous (SC) injections of golimumab 50 mg every 4 weeks.

Intervention Type: DRUG

Methotrexate

Participants will receive methotrexate capsules weekly.

Intervention Type: DRUG

Placebo injection

Participants will receive subcutaneous (SC) injections of placebo every 4 weeks.

Intervention Type: DRUG

Placebo capsules

Participants will receive placebo capsules weekly

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Have a diagnosis of rheumatoid arthritis (RA) (according to the revised 1987 criteria of the ACR) for at least 3 months prior to screening
• Must 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 a MTX dose of >=15 mg/week and <=25 mg/week and stable for at least 4 weeks prior to screening
• Have active RA as defined by persistent disease activity with at least 4 swollen and 4 tender joints, at the time of screening and baseline, and at least 2 of the following 4 criteria: a)C-reactive protein (CRP) >=1.5 mg/dL at screening or erythrocyte sedimentation rate (ESR) by Westergren method of >= 28 mm in the first hour at screening or baseline, b)Morning stiffness of >= 30 minutes at screening and baseline, c)Bone erosion by x-ray and/or magnetic resonance imaging (MRI) prior to first administration of study agent, d)Anti-cyclic citrullinated peptide (anti-CCP) antibody-positive or rheumatoid factor (RF) positive at screening
• If using oral corticosteroids, must be on a stable dose equivalent to <= 10 mg of prednisone/day for at least 2 weeks prior to first administration of study agent
• Are considered eligible according to specified tuberculosis (TB) screening criteria

Exclusion Criteria

• Have inflammatory diseases other than RA that might confound the evaluation of the benefit of golimumab therapy
• Have had treatment with disease-modifying anti-rheumatic drugs (DMARDs)/systemic immunosuppressives other than MTX, during the 4 weeks prior to the first administration of study agent
• Have had prior treatment with biologic anti-tumor necrosis factor (TNF) drugs (infliximab, etanercept, adalimumab)
• Have had history of, or ongoing, chronic or recurrent infectious disease.
• Have serious infection within 2 months prior to first administration of study agent
• Have a history of latent or active granulomatous infection, including TB, histoplasmosis, or coccidioidomycosis, prior to screening

• 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

Mobile, Alabama, United States

Palo Alto, California, United States

Pasadena, California, United States

Upland, California, United States

Ormond Beach, Florida, United States

Palm Harbor, Florida, United States

Moline, Illinois, United States

Kansas City, Missouri, United States

St Louis, Missouri, United States

Lincoln, Nebraska, United States

Omaha, Nebraska, United States

Duncansville, Pennsylvania, United States

Richmond, Virginia, United States

Buenos Aires, , Argentina

Córdoba, , Argentina

Rosario, , Argentina

S.M. de Tucuman, , Argentina

San Miguel de Tucumán, , Argentina

Clayton, , Australia

Maroochydore, , Australia

Melbourne, , Australia

Victoria, British Columbia, Canada

St. John's, Newfoundland and Labrador, Canada

Ottawa, Ontario, Canada

Toronto, Ontario, Canada

Sainte-Foy, Quebec, Canada

Hamilton Ontario, , Canada

Rancagua, , Chile

Santiago, , Chile

Temuco IX, , Chile

Berlin, , Germany

Cologne, , Germany

Hamburg, , Germany

Hanover, , Germany

Leipzig, , Germany

Rostock, , Germany

Budepest, , Hungary

Monterrey, , Mexico

Auckland, , New Zealand

Rotorua, , New Zealand

Timaru, , New Zealand

Elblag, , Poland

Kalisz, , Poland

Szczecin, , Poland

Warsaw, , Poland

Anyang, , South Korea

Daegu, , South Korea

Pusan, , South Korea

Seoul, , South Korea

Kaohsiung County, , Taiwan

Countries

United States; Argentina; Australia; Canada; Chile; Germany; Hungary; Mexico; New Zealand; Poland; South Korea; Taiwan

References

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Reference Type: DERIVED

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Reference Type: DERIVED

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Kay J, Fleischmann R, Keystone E, Hsia EC, Hsu B, Zhou Y, Goldstein N, Braun J. Five-year Safety Data from 5 Clinical Trials of Subcutaneous Golimumab in Patients with Rheumatoid Arthritis, Psoriatic Arthritis, and Ankylosing Spondylitis. J Rheumatol. 2016 Dec;43(12):2120-2130. doi: 10.3899/jrheum.160420. Epub 2016 Nov 1.

Reference Type: DERIVED

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Mack ME, Hsia E, Aletaha D. Comparative Assessment of the Different American College of Rheumatology/European League Against Rheumatism Remission Definitions for Rheumatoid Arthritis for Their Use as Clinical Trial End Points. Arthritis Rheumatol. 2017 Mar;69(3):518-528. doi: 10.1002/art.39945.

Reference Type: DERIVED

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Baker JF, Conaghan PG, Smolen JS, Aletaha D, Shults J, Emery P, Baker DG, Ostergaard M. Development and validation of modified disease activity scores in rheumatoid arthritis: superior correlation with magnetic resonance imaging-detected synovitis and radiographic progression. Arthritis Rheumatol. 2014 Apr;66(4):794-802. doi: 10.1002/art.38304.

Reference Type: DERIVED

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Keystone EC, Genovese MC, Hall S, Miranda PC, Bae SC, Palmer W, Wu Z, Xu S, Hsia EC. Golimumab in patients with active rheumatoid arthritis despite methotrexate therapy: results through 2 years of the GO-FORWARD study extension. J Rheumatol. 2013 Jul;40(7):1097-103. doi: 10.3899/jrheum.120584. Epub 2013 May 15.

Reference Type: DERIVED

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Genovese MC, Han C, Keystone EC, Hsia EC, Buchanan J, Gathany T, Murphy FT, Wu Z, Parasuraman S, Rahman MU. Effect of golimumab on patient-reported outcomes in rheumatoid arthritis: results from the GO-FORWARD study. J Rheumatol. 2012 Jun;39(6):1185-91. doi: 10.3899/jrheum.111195. Epub 2012 Apr 15.

Reference Type: DERIVED

PMID: 22505702 (View on PubMed)

Visvanathan S, Rahman MU, Keystone E, Genovese M, Klareskog L, Hsia E, Mack M, Buchanan J, Elashoff M, Wagner C. Association of serum markers with improvement in clinical response measures after treatment with golimumab in patients with active rheumatoid arthritis despite receiving methotrexate: results from the GO-FORWARD study. Arthritis Res Ther. 2010;12(6):R211. doi: 10.1186/ar3188. Epub 2010 Nov 17.

Reference Type: DERIVED

PMID: 21083889 (View on PubMed)

Other Identifiers

C0524T06

Identifier Type: OTHER

Identifier Source: secondary_id

2004-003296-36

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CR006343

Identifier Type: -

Identifier Source: org_study_id