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

NCT00264550 | Completed Phase 3 Results DMC

• 3 other identifiers: CR006343C0524T062004-003296-36
• Study Type: interventional
• Target: 444
• Locations: 12 countries
• Sites: 50

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.

Conditions

Rheumatoid Arthritis

Keywords

Rheumatoid Arthritis; Golimumab; Methotrexate; Fully Human anti-TNFa monoclonal antibody; Simpony

Outcome Measures

Primary Outcomes (2)

• Number of Participants Who Achieved American College of Rheumatology (ACR) 20 Response at Week 14

  ACR 20 response is defined as a greater than or equal to 20 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 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 14

• Change From Baseline in Health Assessment Questionnaire (HAQ) Score at Week 24

  HAQ is 20-question instrument that assesses the degree of difficulty a person has in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and activities of daily living). Responses in each functional area are scored from 0 (no difficulty), to 3 (inability to perform a task in that area). The average score across the functional areas yields an overall HAQ score which ranges from 0 (no disability) to 3 (completely disabled).

  Baseline (Week 0) and Week 24

Secondary Outcomes (4)

• Number of Participants With Disease Activity Index Score 28 (DAS 28) Using C-reactive Protein (CRP) Response at Week 14

  Week 14

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

  Week 24

• Change From Baseline in Health Assessment Questionnaire (HAQ) Score at Week 14

  Baseline (Week 0) and Week 14

• Change From Baseline in Total Van Der Heijde Modified Sharp (vdH-S) Score at Week 24

  Baseline (Week 0) and Week 24

Study Arms (4)

Group 1: Placebo + Methotrexate

PLACEBO COMPARATOR

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.

Drug: Methotrexate; Drug: Placebo injection

Group 2: Golimumab 100 mg + Placebo

EXPERIMENTAL

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.

Drug: Golimumab 100 mg; Drug: Placebo capsules

Group 3: Golimumab 50 mg + Methotrexate

EXPERIMENTAL

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.

Drug: Golimumab 50 mg; Drug: Methotrexate

Group 4: Golimumab 100 mg + Methotrexate

EXPERIMENTAL

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.

Drug: Golimumab 100 mg; Drug: Methotrexate

Interventions

Golimumab 100 mg DRUG

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

Group 2: Golimumab 100 mg + Placebo; Group 4: Golimumab 100 mg + Methotrexate

Golimumab 50 mg DRUG

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

Group 3: Golimumab 50 mg + Methotrexate

Methotrexate DRUG

Participants will receive methotrexate capsules weekly.

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

Placebo injection DRUG

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

Group 1: Placebo + Methotrexate

Placebo capsules DRUG

Participants will receive placebo capsules weekly

Group 2: Golimumab 100 mg + Placebo

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 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

You may not qualify if:

• 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

Sponsors & Collaborators

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

Study Sites (50)

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Mobile, Alabama, United States

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Palo Alto, California, United States

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Pasadena, California, United States

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Upland, California, United States

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Ormond Beach, Florida, United States

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Palm Harbor, Florida, United States

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Moline, Illinois, United States

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Kansas City, Missouri, United States

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St Louis, Missouri, United States

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Lincoln, Nebraska, United States

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Omaha, Nebraska, United States

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Duncansville, Pennsylvania, United States

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Richmond, Virginia, 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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Clayton, Australia

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Maroochydore, Australia

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Melbourne, Australia

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Victoria, British Columbia, Canada

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St. John's, Newfoundland and Labrador, Canada

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Ottawa, Ontario, Canada

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Toronto, Ontario, Canada

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Sainte-Foy, Quebec, Canada

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Hamilton Ontario, Canada

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Rancagua, Chile

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Santiago, Chile

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Temuco IX, Chile

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Berlin, Germany

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Cologne, Germany

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Hamburg, Germany

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Hanover, Germany

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Leipzig, Germany

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Rostock, Germany

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Budepest, Hungary

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Monterrey, Mexico

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Auckland, New Zealand

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Rotorua, New Zealand

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Timaru, New Zealand

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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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Anyang, South Korea

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Daegu, South Korea

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Pusan, South Korea

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Seoul, South Korea

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Kaohsiung County, Taiwan

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Related Publications (8)

• Leu JH, Adedokun OJ, Gargano C, Hsia EC, Xu Z, Shankar G. Immunogenicity of golimumab and its clinical relevance in patients with rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis. Rheumatology (Oxford). 2019 Mar 1;58(3):441-446. doi: 10.1093/rheumatology/key309.

  PMID: 30412238 DERIVED

• George MD, Ostergaard M, Conaghan PG, Emery P, Baker DG, Baker JF. Obesity and rates of clinical remission and low MRI inflammation in rheumatoid arthritis. Ann Rheum Dis. 2017 Oct;76(10):1743-1746. doi: 10.1136/annrheumdis-2017-211569. Epub 2017 Jun 12.

  PMID: 28606966 DERIVED

• 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

• 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.

  PMID: 27696724 DERIVED

• 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.

  PMID: 24757132 DERIVED

• 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.

  PMID: 23678153 DERIVED

• 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.

  PMID: 22505702 DERIVED

• 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.

  PMID: 21083889 DERIVED

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

golimumab; Methotrexate

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

Limitations and Caveats

The count of patients with any nonserious adverse events (NAE) excludes patients who only had NAE that occurred in \<= 5% of patients. This information may vary from existing approved labeling and publications due to the requirement of this website.

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: GT60
• 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: September 1, 2007
• Study Completion: May 1, 2012
• Last Updated: April 29, 2014
• Results First Posted: March 21, 2014

Record last verified: 2014-04

Locations

KR (4); CA (6); DE (6); ME (1); AU (3); NZ (3); PL (4); HU (1); US (13); AR (5); TW (1); CL (3)