- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00264550
An Efficacy and Safety Study of Golimumab in Patients With Active Rheumatoid Arthritis Despite Methotrexate Therapy (GO-FORWARD)
April 14, 2014 updated by: Centocor, Inc.
A Multicenter, Randomized, Double-blind, Placebo-controlledTrial of Golimumab, a Fully Human Anti-TNFa MonoclonalAntibody, Administered Subcutaneously, in Subjects With ActiveRheumatoid Arthritis Despite Methotrexate Therapy
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.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
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.
Study Type
Interventional
Enrollment (Actual)
444
Phase
- Phase 3
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Buenos Aires, Argentina
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Cordoba, Argentina
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Rosario, Argentina
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S.M. De Tucuman, Argentina
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San Miguel De Tucuman, Argentina
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Clayton, Australia
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Maroochydore, Australia
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Melbourne, Australia
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Hamilton Ontario, Canada
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British Columbia
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Victoria, British Columbia, Canada
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Newfoundland and Labrador
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St. John'S, Newfoundland and Labrador, Canada
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Ontario
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Ottawa, Ontario, Canada
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Toronto, Ontario, Canada
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Quebec
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Sainte Foy, Quebec, Canada
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Rancagua, Chile
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Santiago, Chile
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Santiago De Chile, Chile
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Temuco Ix, Chile
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Berlin, Germany
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Hamburg, Germany
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Hannover, Germany
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Köln, Germany
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Leipzig, Germany
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Rostock, Germany
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Budepest, Hungary
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Anyang, Korea, Republic of
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Daegu, Korea, Republic of
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Pusan, Korea, Republic of
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Seoul, Korea, Republic of
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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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Warszawa N/A, Poland
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Kaohsiung County, Taiwan
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Alabama
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Mobile, Alabama, United States
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California
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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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Florida
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Ormond Beach, Florida, United States
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Palm Harbor, Florida, United States
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Illinois
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Moline, Illinois, United States
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Missouri
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Kansas City, Missouri, United States
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Saint Louis, Missouri, United States
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Nebraska
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Lincoln, Nebraska, United States
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Omaha, Nebraska, United States
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Pennsylvania
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Duncansville, Pennsylvania, United States
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Virginia
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Richmond, Virginia, United States
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Placebo Comparator: 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.
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Participants will receive methotrexate capsules weekly.
Participants will receive subcutaneous (SC) injections of placebo every 4 weeks.
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Experimental: 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.
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Participants will receive subcutaneous (SC) injections of golimumab 100 mg every 4 weeks.
Participants will receive placebo capsules weekly
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Experimental: 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.
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Participants will receive methotrexate capsules weekly.
Participants will receive subcutaneous (SC) injections of golimumab 50 mg every 4 weeks.
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Experimental: 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.
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Participants will receive methotrexate capsules weekly.
Participants will receive subcutaneous (SC) injections of golimumab 100 mg every 4 weeks.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Number of Participants Who Achieved American College of Rheumatology (ACR) 20 Response at Week 14
Time Frame: Week 14
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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.
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Week 14
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Change From Baseline in Health Assessment Questionnaire (HAQ) Score at Week 24
Time Frame: Baseline (Week 0) and Week 24
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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).
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Baseline (Week 0) and Week 24
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Number of Participants With Disease Activity Index Score 28 (DAS 28) Using C-reactive Protein (CRP) Response at Week 14
Time Frame: Week 14
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DAS 28 using CRP is an index to measure the disease activity in participants with rheumatoid arthritis which combines tender joint count (28 joints), swollen joint count (28 joints), CRP value, and participant's global assessment of disease activity (using a Visual Analog Scale of 0 to 100 mm).
The DAS 28 score ranges from 0 (best) to 10 (worst).
Participants are considered to have a DAS 28 response if they have a score of <= 3.2 (good response) or > 3.2 to 5.1 (moderate response).
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Week 14
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Number of Participants Who Achieved American College of Rheumatology 20 (ACR 20) Response at Week 24
Time Frame: Week 24
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An 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 (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 (CRP).
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Week 24
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Change From Baseline in Health Assessment Questionnaire (HAQ) Score at Week 14
Time Frame: Baseline (Week 0) and Week 14
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The 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).
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Baseline (Week 0) and Week 14
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Change From Baseline in Total Van Der Heijde Modified Sharp (vdH-S) Score at Week 24
Time Frame: Baseline (Week 0) and Week 24
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The vdH-S score is the sum of joint erosion score and joint-space narrowing (JSN) score.
The total score ranges from 0 (best) to 448 (worst) with higher scores indicating more joint damage.
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Baseline (Week 0) and Week 24
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
December 1, 2005
Primary Completion (Actual)
September 1, 2007
Study Completion (Actual)
May 1, 2012
Study Registration Dates
First Submitted
December 11, 2005
First Submitted That Met QC Criteria
December 11, 2005
First Posted (Estimate)
December 13, 2005
Study Record Updates
Last Update Posted (Estimate)
April 29, 2014
Last Update Submitted That Met QC Criteria
April 14, 2014
Last Verified
April 1, 2014
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Immune System Diseases
- Autoimmune Diseases
- Joint Diseases
- Musculoskeletal Diseases
- Rheumatic Diseases
- Connective Tissue Diseases
- Arthritis
- Arthritis, Rheumatoid
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Nucleic Acid Synthesis Inhibitors
- Enzyme Inhibitors
- Anti-Inflammatory Agents
- Antirheumatic Agents
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Dermatologic Agents
- Reproductive Control Agents
- Abortifacient Agents, Nonsteroidal
- Abortifacient Agents
- Folic Acid Antagonists
- Tumor Necrosis Factor Inhibitors
- Antibodies, Monoclonal
- Methotrexate
- Golimumab
Other Study ID Numbers
- CR006343
- C0524T06 (Other Identifier: Centocor)
- 2004-003296-36 (EudraCT Number)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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