A Study of the Safety and Efficacy of Golimumab in Subjects With Rheumatoid Arthritis That Are Methotrexate-naive

NCT ID: NCT00264537

Last Updated: 2014-09-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 637 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-12-31
• Study Completion Date: 2012-06-30

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of golimumab, alone or in combination with methotrexate, as compared to methotrexate alone in rheumatoid arthritis subjects who have not been previously treated with methotrexate.

Detailed Description

Golimumab is a fully human protein (antibody) which binds to tumor necrosis factor (TNFa). TNFa is increased in patients with rheumatoid arthritis (RA), and plays a major role in causing the joint pain, swelling, and damage from RA. Other marketed drugs that target TNFa (anti-TNFa drugs) have been shown to be effective in reducing the symptoms, signs, and joint damage of RA, but have limitations with respect to safety and ease of use. This is a randomized, double-blind, placebo-controlled trial of the efficacy and safety of a new anti-TNFa drug, golimumab, at 2 doses, injected under the skin every 4 weeks, alone or in combination with methotrexate, compared with methotrexate alone, in subjects with active RA who have not been previously treated with methotrexate. The study hypothesis is that golimumab, alone or in combination with methotrexate, will be more effective in treatment of RA than methotrexate alone, as measured by the American College of Rheumatology (ACR) response criteria and change from baseline in van der Heide Modified Sharp (vdH-S) score, without causing unacceptable significant adverse effects. The ACR response criteria were designed to determine the percentage of subjects who have achieved a certain level of improvement in their signs and symptoms of rheumatoid arthritis. The vdH-S score is a measurement of the amount of joint damage in a subject as seen by x-ray. Other secondary measures of effectiveness include the Health Assessment Questionnaire (HAQ), which is a series of questions that measure a subject's impairment in physical function caused by RA. Golimumab 50 mg or 100 mg, or placebo injections under the skin every 4 weeks until Week52. Methotrexate (MTX) or placebo capsules will be given in addition. At Week52, subjects on MTX alone with joint pain or swelling get golimumab 50mg, and all subjects receive golimumab for about 4 more years.

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 injections (SC) every 4 weeks from Week 0 for up to 5 years (unless early escape at week 28); Methotrexate - 10 to 20 mg weekly from Week 0 for up to 5 years; Golimumab - if early escape, 50 mg SC injections every 4 weeks from Week 28 up to 5 years; Golimumab - Dr's discretion after unblinding (in participants receiving methotrexate plus placebo), 50 mg SC injections every 4 weeks up to 5 years; Golimumab- Dr's discretion after unblinding, dose adjusted from 50 to 100 mg and from 100 to 50mg. Duration of the blinded period will be until the week-52 database lock.

Group Type: EXPERIMENTAL

Placebo injections

Intervention Type: DRUG

SC injections

Methotrexate capsules

Intervention Type: DRUG

Methotrexate capsules will be filled with microcrystalline cellulose (Avicel PH 102) and a 2.5 mg methotrexate tablet.

Golimumab 50 mg injections

Intervention Type: BIOLOGICAL

SC injections

Golimumab 100 mg injections

Intervention Type: BIOLOGICAL

SC injections

Group 2: Golimumab 100 mg + Placebo

Golimumab 100 mg SC injections every 4 weeks from Week 0 for up to 5 years; placebo capsules weekly from Week 0 for up to 5 years (unless early escape at Week 28); Methotrexate - if early escape, 10 to 20 mg weekly from Week 28 up to 5 years; Methotrexate - Dr's discretion after unblinding (in participants receiving golimumab plus placebo) 10 to 20 mg weekly for up to 5 years; 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

Placebo capsules

Intervention Type: DRUG

Placebo capsules will be filled with microcrystalline cellulose (Avicel PH 102).

Methotrexate capsules

Intervention Type: DRUG

Methotrexate capsules will be filled with microcrystalline cellulose (Avicel PH 102) and a 2.5 mg methotrexate tablet.

Golimumab 50 mg injections

Intervention Type: BIOLOGICAL

SC injections

Golimumab 100 mg injections

Intervention Type: BIOLOGICAL

SC injections

Group 3: Golimumab 50 mg + Methotrexate

Golimumab 50 mg SC injections every 4 weeks from Week 0 for up to 5 years (unless early escape at week 28); Methotrexate - 10 to 20 mg weekly from Week 0 for up to 5 years; Golimumab - if early escape, 100 mg SC injections every 4 weeks from Week 28 for up to 5 yrs; Golimumab - Dr's discretion after unblinding, dose adjusted from 50 to 100 mg and from 100 to 50mg. Duration of the blinded period will be until the week-52 database lock.

Group Type: EXPERIMENTAL

Methotrexate capsules

Intervention Type: DRUG

Methotrexate capsules will be filled with microcrystalline cellulose (Avicel PH 102) and a 2.5 mg methotrexate tablet.

Golimumab 50 mg injections

Intervention Type: BIOLOGICAL

SC injections

Golimumab 100 mg injections

Intervention Type: BIOLOGICAL

SC injections

Group 4: Golimumab 100 mg + Methotrexate

Golimumab 100 mg SC injections every 4 weeks from Week 0 for up to 5 years; Methotrexate - 10 to 20 mg weekly from Week 0 for up to 5 years; 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

Methotrexate capsules

Intervention Type: DRUG

Methotrexate capsules will be filled with microcrystalline cellulose (Avicel PH 102) and a 2.5 mg methotrexate tablet.

Golimumab 50 mg injections

Intervention Type: BIOLOGICAL

SC injections

Golimumab 100 mg injections

Intervention Type: BIOLOGICAL

SC injections

Interventions

Placebo injections

SC injections

Intervention Type: DRUG

Placebo capsules

Placebo capsules will be filled with microcrystalline cellulose (Avicel PH 102).

Intervention Type: DRUG

Methotrexate capsules

Methotrexate capsules will be filled with microcrystalline cellulose (Avicel PH 102) and a 2.5 mg methotrexate tablet.

Intervention Type: DRUG

Golimumab 50 mg injections

SC injections

Intervention Type: BIOLOGICAL

Golimumab 100 mg injections

SC injections

Intervention Type: BIOLOGICAL

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 first administration of study agent
• Are methotrexate (MTX)-naïve (ie, have not received more than 3 weekly doses of MTX for RA at any time)
• 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 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.

Exclusion Criteria

• Can not have inflammatory diseases other than RA that might confound the evaluation of the benefit of golimumab therapy
• No treatment with disease-modifying anti-rheumatic drugs (DMARDs)/systemic immunosuppressives during the 4 weeks prior to the first administration of study agent
• No prior treatment with biologic anti-TNF drugs (infliximab, etanercept, adalimumab)
• No history of, or ongoing, chronic or recurrent infectious disease
• No serious infection within 2 months prior to first administration of study agent.

• 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

Birmingham, Alabama, United States

Mobile, Alabama, United States

Upland, California, United States

Jacksonville, Florida, United States

Miami, Florida, United States

Coeur d'Alene, Idaho, United States

Moline, Illinois, United States

Springfield, Illinois, United States

Kansas City, Kansas, United States

Witchita, Kansas, United States

Saint Paul, Minnesota, United States

Kansas City, Missouri, United States

Lincoln, Nebraska, United States

Charlotte, North Carolina, United States

Duncansville, Pennsylvania, United States

Dallas, Texas, United States

Fort Worth, Texas, United States

Lubbock, Texas, United States

Buenos Aires, , Argentina

Córdoba, , Argentina

Rosario, , Argentina

S.M. de Tucuman, , Argentina

San Miguel de Tucumán, , Argentina

Maroochydore, , Australia

Melbourne, , Australia

Vienna, , Austria

Brussels, , Belgium

Liège, , Belgium

Winnipeg, Manitoba, Canada

St. John's, Newfoundland and Labrador, Canada

Rancagua, , Chile

Santiago, , Chile

Budapest, , Hungary

Gyula, , Hungary

Szombathely, , Hungary

Bangalore, , India

Lucknow Gpo, , India

Secunderabad, , India

Precinct 7, , Malaysia

Saemban, , Malaysia

Selayang Baru Utara, , Malaysia

Auckland, , New Zealand

Timaru, , New Zealand

Cebu, , Philippines

Manila, , Philippines

Quezon, , Philippines

Bialystok, , Poland

Elblag, , Poland

Kalisz, , Poland

Szczecin, , Poland

Warsaw, , Poland

Moscow, , Russia

Saratov, , Russia

Yaroslavl, , Russia

Singapore, , Singapore

Daejeon, , South Korea

Incheon, , South Korea

Seoul, , South Korea

Suwon, , South Korea

Madrid, , Spain

Santander, , Spain

Seville, , Spain

Valencia, , Spain

Kaohsiung City, , Taiwan

Taichung, , Taiwan

Taipei, , Taiwan

Tiachung, , Taiwan

Bangkok, , Thailand

Chiang Mai, , Thailand

Dnipropetrovsk, , Ukraine

Donetsk, , Ukraine

Kharkiv, , Ukraine

Kiev, , Ukraine

Leeds, , United Kingdom

London, , United Kingdom

Countries

United States; Argentina; Australia; Austria; Belgium; Canada; Chile; Hungary; India; Malaysia; New Zealand; Philippines; Poland; Russia; Singapore; South Korea; Spain; Taiwan; Thailand; Ukraine; United Kingdom

References

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

PMID: 27803138 (View on PubMed)

Baker JF, Conaghan PG, Emery P, Baker DG, Ostergaard M. Relationship of patient-reported outcomes with MRI measures in rheumatoid arthritis. Ann Rheum Dis. 2017 Mar;76(3):486-490. doi: 10.1136/annrheumdis-2016-209463. Epub 2016 Jul 18.

Reference Type: DERIVED

PMID: 27432355 (View on PubMed)

Emery P, Fleischmann RM, Hsia EC, Xu S, Zhou Y, Baker D. Efficacy of golimumab plus methotrexate in methotrexate-naive patients with severe active rheumatoid arthritis. Clin Rheumatol. 2014 Sep;33(9):1239-46. doi: 10.1007/s10067-014-2731-y. Epub 2014 Jul 9.

Reference Type: DERIVED

PMID: 25005327 (View on PubMed)

Emery P, Fleischmann RM, Doyle MK, Strusberg I, Durez P, Nash P, Amante E, Churchill M, Park W, Pons-Estel B, Xu W, Xu S, Wu Z, Hsia EC. Golimumab, a human anti-tumor necrosis factor monoclonal antibody, injected subcutaneously every 4 weeks in patients with active rheumatoid arthritis who had never taken methotrexate: 1-year and 2-year clinical, radiologic, and physical function findings of a phase III, multicenter, randomized, double-blind, placebo-controlled study. Arthritis Care Res (Hoboken). 2013 Nov;65(11):1732-42. doi: 10.1002/acr.22072.

Reference Type: DERIVED

PMID: 23861303 (View on PubMed)

Ostergaard M, Emery P, Conaghan PG, Fleischmann R, Hsia EC, Xu W, Rahman MU. Significant improvement in synovitis, osteitis, and bone erosion following golimumab and methotrexate combination therapy as compared with methotrexate alone: a magnetic resonance imaging study of 318 methotrexate-naive rheumatoid arthritis patients. Arthritis Rheum. 2011 Dec;63(12):3712-22. doi: 10.1002/art.30592.

Reference Type: DERIVED

PMID: 22127693 (View on PubMed)

Other Identifiers

GO-BEFORE

Identifier Type: -

Identifier Source: secondary_id

C0524T05

Identifier Type: -

Identifier Source: secondary_id

CR006331

Identifier Type: -

Identifier Source: org_study_id