An Efficacy and Safety Study of Golimumab in Patients With Active Rheumatoid Arthritis Despite Methotrexate Therapy (GO-FORWARD)
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| ClinicalTrials.gov Identifier: NCT00264550 |
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Recruitment Status :
Completed
First Posted : December 13, 2005
Results First Posted : March 21, 2014
Last Update Posted : April 29, 2014
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Sponsor:
Centocor, Inc.
Collaborator:
Schering-Plough
Information provided by (Responsible Party):
Centocor, Inc.
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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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Rheumatoid Arthritis | Drug: Golimumab 100 mg Drug: Golimumab 50 mg Drug: Methotrexate Drug: Placebo injection Drug: Placebo capsules | Phase 3 |
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 (Clinical Trial) |
| Actual Enrollment : | 444 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
| Primary Purpose: | Treatment |
| Official Title: | 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 |
| Study Start Date : | December 2005 |
| Actual Primary Completion Date : | September 2007 |
| Actual Study Completion Date : | May 2012 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Rheumatoid arthritis
| 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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Drug: Methotrexate
Participants will receive methotrexate capsules weekly. Drug: Placebo injection 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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Drug: Golimumab 100 mg
Participants will receive subcutaneous (SC) injections of golimumab 100 mg every 4 weeks. Drug: Placebo capsules 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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Drug: Golimumab 50 mg
Participants will receive subcutaneous (SC) injections of golimumab 50 mg every 4 weeks. Drug: Methotrexate Participants will receive methotrexate capsules weekly. |
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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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Drug: Golimumab 100 mg
Participants will receive subcutaneous (SC) injections of golimumab 100 mg every 4 weeks. Drug: Methotrexate Participants will receive methotrexate capsules weekly. |
Primary Outcome Measures :
- Number of Participants Who Achieved American College of Rheumatology (ACR) 20 Response at Week 14 [ Time Frame: 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.
- Change From Baseline in Health Assessment Questionnaire (HAQ) Score at Week 24 [ Time Frame: Baseline (Week 0) and 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).
Secondary Outcome Measures :
- Number of Participants With Disease Activity Index Score 28 (DAS 28) Using C-reactive Protein (CRP) Response at Week 14 [ Time Frame: Week 14 ]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).
- Number of Participants Who Achieved American College of Rheumatology 20 (ACR 20) Response at Week 24 [ Time Frame: Week 24 ]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).
- Change From Baseline in Health Assessment Questionnaire (HAQ) Score at Week 14 [ Time Frame: Baseline (Week 0) and Week 14 ]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).
- Change From Baseline in Total Van Der Heijde Modified Sharp (vdH-S) Score at Week 24 [ Time Frame: Baseline (Week 0) and Week 24 ]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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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00264550
Locations
Show 52 study locations
Sponsors and Collaborators
Centocor, Inc.
Schering-Plough
Investigators
| Study Director: | Centocor, Inc. Clinical Trial | Centocor, Inc. |
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Centocor, Inc. |
| ClinicalTrials.gov Identifier: | NCT00264550 |
| Other Study ID Numbers: |
CR006343 C0524T06 ( Other Identifier: Centocor ) 2004-003296-36 ( EudraCT Number ) |
| First Posted: | December 13, 2005 Key Record Dates |
| Results First Posted: | March 21, 2014 |
| Last Update Posted: | April 29, 2014 |
| Last Verified: | April 2014 |
Keywords provided by Centocor, Inc.:
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Rheumatoid Arthritis Golimumab Methotrexate Fully Human anti-TNFa monoclonal antibody Simpony |
Additional relevant MeSH terms:
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Arthritis Arthritis, Rheumatoid Joint Diseases Musculoskeletal Diseases Rheumatic Diseases Connective Tissue Diseases Autoimmune Diseases Immune System Diseases Golimumab Methotrexate Antibodies, Monoclonal Abortifacient Agents, Nonsteroidal Abortifacient Agents Reproductive Control Agents |
Physiological Effects of Drugs Antimetabolites, Antineoplastic Antimetabolites Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Dermatologic Agents Enzyme Inhibitors Folic Acid Antagonists Immunosuppressive Agents Immunologic Factors Antirheumatic Agents Nucleic Acid Synthesis Inhibitors Tumor Necrosis Factor Inhibitors Anti-Inflammatory Agents |