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

NCT00264537 | Completed Phase 3 Results DMC

• 3 other identifiers: CR006331GO-BEFOREC0524T05
• Study Type: interventional
• Target: 637
• Locations: 20 countries
• Sites: 73

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.

Conditions

Rheumatoid Arthritis

Keywords

Rheumatoid Arthritis; Methotrexate Naïve; subcutaneous injection

Outcome Measures

Primary Outcomes (2)

• Number of Participants Who Achieved American College of Rheumatology (ACR) 50 Response at Week 24

  ACR 50 response is defined as a greater than or equal to 50 percent improvement from baseline in: 1. Swollen joint count (66 joints) and tender joint count (68 joints) 2. greater than or equal to 50 percentage improvement in 3 of the following 5 assessments: a. Patient's assessment of pain by the Visual Analogue Scale (VAS) (0-10 cm) b.Patient's Global Assessment of Disease activity VAS (0-10 cm) c. Physician's Global Assessment of Disease Activity VAS (0-10 cm) d. Patient's assessment of physical function as measured by the Health Assessment Questionnaire (HAQ) e. C reactive protein.

  Week 24

• Change From Baseline in Total Van Der Heijde Modified Sharp (vdH-S) Score at Week 52

  The vdH-S score is the sum of the joint erosion score and the joint-space narrowing (JSN) score. The total score ranges from 0 (best) to 448 (worst) with higher scores indicating more joint damage.

  Baseline and Week 52

Secondary Outcomes (3)

• Number of Participants Who Achieved American College of Rheumatology (ACR) 20 Response at Week 24

  Week 24

• Number of Patients With Abnormal Baseline C-reactive Protein (CRP) Who Achieved American College of Rheumatology (ACR) 50 Response at Week 24

  Week 24

• Change From Baseline in Total Van Der Heijde Modified Sharp (vdH-S) Score at Week 52 in Patients With Abnormal C-reactive Protein (CRP Greater Than 1.0 mg/dL) at Baseline

  Baseline and Week 52

Study Arms (4)

Group 1: Placebo + Methotrexate

EXPERIMENTAL

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.

Drug: Placebo injections; Drug: Methotrexate capsules; Biological: Golimumab 50 mg injections; Biological: Golimumab 100 mg injections

Group 2: Golimumab 100 mg + Placebo

EXPERIMENTAL

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.

Drug: Placebo capsules; Drug: Methotrexate capsules; Biological: Golimumab 50 mg injections; Biological: Golimumab 100 mg injections

Group 3: Golimumab 50 mg + Methotrexate

EXPERIMENTAL

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.

Drug: Methotrexate capsules; Biological: Golimumab 50 mg injections; Biological: Golimumab 100 mg injections

Group 4: Golimumab 100 mg + Methotrexate

EXPERIMENTAL

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.

Drug: Methotrexate capsules; Biological: Golimumab 50 mg injections; Biological: Golimumab 100 mg injections

Interventions

Placebo injections DRUG

SC injections

Group 1: Placebo + Methotrexate

Placebo capsules DRUG

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

Group 2: Golimumab 100 mg + Placebo

Methotrexate capsules DRUG

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

Group 1: Placebo + Methotrexate; Group 2: Golimumab 100 mg + Placebo; Group 3: Golimumab 50 mg + Methotrexate; Group 4: Golimumab 100 mg + Methotrexate

Golimumab 50 mg injections BIOLOGICAL

SC injections

Group 1: Placebo + Methotrexate; Group 2: Golimumab 100 mg + Placebo; Group 3: Golimumab 50 mg + Methotrexate; Group 4: Golimumab 100 mg + Methotrexate

Golimumab 100 mg injections BIOLOGICAL

SC injections

Group 1: Placebo + Methotrexate; Group 2: Golimumab 100 mg + Placebo; Group 3: Golimumab 50 mg + Methotrexate; Group 4: Golimumab 100 mg + Methotrexate

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Centocor, Inc.: lead
• Schering-Plough: collaborator

Study Sites (75)

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Birmingham, Alabama, United States

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Mobile, Alabama, United States

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Upland, California, United States

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Jacksonville, Florida, United States

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Miami, Florida, United States

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Coeur d'Alene, Idaho, United States

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Moline, Illinois, United States

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Springfield, Illinois, United States

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Kansas City, Kansas, United States

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Witchita, Kansas, United States

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Saint Paul, Minnesota, United States

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Kansas City, Missouri, United States

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Lincoln, Nebraska, United States

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Charlotte, North Carolina, United States

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Duncansville, Pennsylvania, United States

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Dallas, Texas, United States

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Fort Worth, Texas, United States

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Lubbock, Texas, United States

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Buenos Aires, Argentina

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Córdoba, Argentina

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Rosario, Argentina

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S.M. de Tucuman, Argentina

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San Miguel de Tucumán, Argentina

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Maroochydore, Australia

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Melbourne, Australia

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Vienna, Austria

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Brussels, Belgium

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Liège, Belgium

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Winnipeg, Manitoba, Canada

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St. John's, Newfoundland and Labrador, Canada

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Rancagua, Chile

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Santiago, Chile

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Budapest, Hungary

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Gyula, Hungary

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Szombathely, Hungary

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Bangalore, India

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Lucknow Gpo, India

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Secunderabad, India

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Precinct 7, Malaysia

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Saemban, Malaysia

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Selayang Baru Utara, Malaysia

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Auckland, New Zealand

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Timaru, New Zealand

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Cebu, Philippines

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Manila, Philippines

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Quezon, Philippines

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Bialystok, Poland

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Elblag, Poland

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Kalisz, Poland

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Szczecin, Poland

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Warsaw, Poland

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Moscow, Russia

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Saratov, Russia

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Yaroslavl, Russia

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Singapore, Singapore

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Daejeon, South Korea

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Incheon, South Korea

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Seoul, South Korea

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Suwon, South Korea

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Madrid, Spain

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Santander, Spain

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Seville, Spain

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Valencia, Spain

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Kaohsiung City, Taiwan

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Taichung, Taiwan

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Taipei, Taiwan

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Tiachung, Taiwan

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Bangkok, Thailand

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Chiang Mai, Thailand

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Dnipropetrovsk, Ukraine

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Donetsk, Ukraine

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Kharkiv, Ukraine

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Kiev, Ukraine

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Leeds, United Kingdom

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London, United Kingdom

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Related Publications (5)

• 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.

  PMID: 27803138 DERIVED

• 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.

  PMID: 27432355 DERIVED

• 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.

  PMID: 25005327 DERIVED

• 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.

  PMID: 23861303 DERIVED

• 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.

  PMID: 22127693 DERIVED

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

Methotrexate; golimumab; Injections

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Drug Administration Routes; Drug Therapy; Therapeutics

Limitations and Caveats

The count of patients with any nonserious adverse events (NAE) excludes patients who only had NAE that occurred in less than or equal to 5% of patients. This information may vary from existing approved labeling and publications.

Results Point of Contact

• Title: Director Clinical Research
• Organization: Centocor Research & Development, Inc.

1-800-457-6399

Study Officials

• Centocor, Inc. Clinical Trial

  Centocor, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 11, 2005
• First Posted: December 13, 2005
• Study Start: December 1, 2005
• Primary Completion: April 1, 2008
• Study Completion: June 1, 2012
• Last Updated: September 5, 2014
• Results First Posted: July 13, 2009

Record last verified: 2014-08

Locations

AR (5); MY (3); CA (2); HU (3); RU (3); ES (4); TH (2); GB (2); AU (1); SG (1); NZ (2); PH (3); US (18); TW (4); KR (4); UA (4); CL (2); BE (2); IN (3); PL (5)