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

This study has been completed.
Sponsor:
Collaborator:
Schering-Plough
Information provided by (Responsible Party):
Centocor, Inc.
ClinicalTrials.gov Identifier:
NCT00264537
First received: December 11, 2005
Last updated: August 27, 2014
Last verified: August 2014
  Purpose

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.


Condition Intervention Phase
Rheumatoid Arthritis
Drug: Placebo injections
Drug: Placebo capsules
Drug: Methotrexate capsules
Biological: Golimumab 50 mg injections
Biological: Golimumab 100 mg injections
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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 Methotrexate-naive Subjects With Active Rheumatoid Arthritis

Resource links provided by NLM:


Further study details as provided by Centocor, Inc.:

Primary Outcome Measures:
  • Number of Participants Who Achieved American College of Rheumatology (ACR) 50 Response at Week 24 [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Total Van Der Heijde Modified Sharp (vdH-S) Score at Week 52 [ Time Frame: Baseline and Week 52 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Number of Participants Who Achieved American College of Rheumatology (ACR) 20 Response at Week 24 [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    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 20 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.

  • Number of Patients With Abnormal Baseline C-reactive Protein (CRP) Who Achieved American College of Rheumatology (ACR) 50 Response at Week 24 [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    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.

  • 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 [ Time Frame: Baseline and Week 52 ] [ Designated as safety issue: No ]
    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.


Enrollment: 637
Study Start Date: December 2005
Study Completion Date: June 2012
Primary Completion Date: April 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Drug: Placebo injections
SC injections
Drug: Methotrexate capsules
Methotrexate capsules will be filled with microcrystalline cellulose (Avicel PH 102) and a 2.5 mg methotrexate tablet.
Biological: Golimumab 50 mg injections
SC injections
Biological: Golimumab 100 mg injections
SC injections
Experimental: 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.
Drug: Placebo capsules
Placebo capsules will be filled with microcrystalline cellulose (Avicel PH 102).
Drug: Methotrexate capsules
Methotrexate capsules will be filled with microcrystalline cellulose (Avicel PH 102) and a 2.5 mg methotrexate tablet.
Biological: Golimumab 50 mg injections
SC injections
Biological: Golimumab 100 mg injections
SC injections
Experimental: 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.
Drug: Methotrexate capsules
Methotrexate capsules will be filled with microcrystalline cellulose (Avicel PH 102) and a 2.5 mg methotrexate tablet.
Biological: Golimumab 50 mg injections
SC injections
Biological: Golimumab 100 mg injections
SC injections
Experimental: 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.
Drug: Methotrexate capsules
Methotrexate capsules will be filled with microcrystalline cellulose (Avicel PH 102) and a 2.5 mg methotrexate tablet.
Biological: Golimumab 50 mg injections
SC injections
Biological: Golimumab 100 mg injections
SC injections

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00264537

  Show 76 Study Locations
Sponsors and Collaborators
Centocor, Inc.
Schering-Plough
Investigators
Study Director: Centocor, Inc. Clinical Trial Centocor, Inc.
  More Information

No publications provided by Centocor, Inc.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Centocor, Inc.
ClinicalTrials.gov Identifier: NCT00264537     History of Changes
Other Study ID Numbers: CR006331, GO-BEFORE, C0524T05
Study First Received: December 11, 2005
Results First Received: May 21, 2009
Last Updated: August 27, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Centocor, Inc.:
Rheumatoid Arthritis
Methotrexate Naïve
subcutaneous injection

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Autoimmune Diseases
Connective Tissue Diseases
Immune System Diseases
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Methotrexate
Abortifacient Agents
Abortifacient Agents, Nonsteroidal
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antirheumatic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Pharmacologic Actions
Physiological Effects of Drugs
Reproductive Control Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on November 27, 2014