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

Sponsor:	Centocor, Inc.
Collaborator:	Schering-Plough
Information provided by:	Centocor, Inc.
ClinicalTrials.gov Identifier:	NCT00264537

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	Biological: golimumab Drug: placebo; methotrexate Biological: Golimumab Drug: golimumab; methotrexate	Phase III

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-na�ve Subjects With Active Rheumatoid Arthritis

Resource links provided by NLM:

MedlinePlus related topics: Rheumatoid Arthritis

Drug Information available for: Methotrexate Golimumab

U.S. FDA Resources

Further study details as provided by Centocor, Inc.:

Primary Outcome Measures:

American College of Rheumatology 50 Response at Week 24 [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
ACR 50 response is an improvement of >= 50% from baseline in both the tender and swollen joint count and in at least 3 of the 5 assessments ( patient's assessment of pain visual analog scale (VAS), patient's global assessemnt of disease activity VAS scale, Physician's global assessment of disease activity VAS scale,HAQ and CRP)

Secondary Outcome Measures:

American College of Rheumatology 20 Response at Week 24 [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
ACR 20 response is an improvement of >= 20% from baseline in both the tender and swollen joint count and in at least 3 of the 5 assessments ( patient's assessment of pain visual analog scale (VAS), patient's global assessemnt of disease activity VAS scale, Physician's global assessment of disease activity VAS scale,HAQ and CRP)
American College of Rheumatology 50 Response at Week 24 in Patients With Abnormal C-reactive Protein at Baseline [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
Number of patients with abnormal baseline C-reactive protein (CRP) who achieved an American College of Rheumatology (ACR) 50 at Week (Wk) 24. ACR 50 response is an improvement of >= 50% from baseline in both the tender and swollen joint count and in at least 3 of the 5 assessments ( patient's assessment of pain visual analog scale (VAS), patient's global assessemnt of disease activity VAS scale, Physician's global assessment of disease activity VAS scale,HAQ and CRP)

Enrollment:	637
Study Start Date:	November 2005
Estimated Study Completion Date:	June 2012
Primary Completion Date:	June 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 004 Golimumab 100 mg sc injections every 4 wks from wk 0 up to 5 yrs; Methotrexate - 10-20 mg for up to 5 years	Biological: Golimumab 100 mg sc injections every 4 wks from wk 0 up to 5 yrs; Methotrexate - 10-20 mg for up to 5 years
Experimental: 003 golimumab 50 mg sc injections every 4 wks from wk0-48 (Wk 28 if early escape);Methotrexate - 10-20 mg for up to 5 years; Golimumab - If early escape, 100 mg beginning at wk 28 for up to 5 yrs; Golimumab - Dr's discretion after unblinding, dose adjust from 50 to100 mg	Biological: golimumab 50 mg sc injections every 4 wks from wk0-48 (Wk 28 if early escape);Methotrexate - 10-20 mg for up to 5 years; Golimumab - If early escape, 100 mg beginning at wk 28 for up to 5 yrs; Golimumab - Dr's discretion after unblinding, dose adjust from 50 to100 mg
Placebo Comparator: 001 placebo; methotrexate SC injections every 4 wks from wk0 to wk 48 (unless early escape at wk 28);methotrexate-10-20mg for up to 5 years;golimumab-If early escape, 50mg sc injection every 4 wks from wk 28 up to 5 yrs; golimumab-Dr's discretion after unblinding, dose adjust from 50 to 100 mg	Drug: placebo; methotrexate SC injections every 4 wks from wk0 to wk 48 (unless early escape at wk 28);methotrexate-10-20mg for up to 5 years;golimumab-If early escape, 50mg sc injection every 4 wks from wk 28 up to 5 yrs; golimumab-Dr's discretion after unblinding, dose adjust from 50 to 100 mg
Experimental: 002 golimumab; methotrexate 100mg sc injection every 4 wks for up to 5 yrs;methotrexate- 4-8 capsules weekly during blinded period;methotrexate - If early escape may start 10mg weekly during blinded period; methotrexate - Dr's discretion, adjust weekly dose after unblinding	Drug: golimumab; methotrexate 100mg sc injection every 4 wks for up to 5 yrs;methotrexate- 4-8 capsules weekly during blinded period;methotrexate - If early escape may start 10mg weekly during blinded period; methotrexate - Dr's discretion, adjust weekly dose after unblinding

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 Heijde 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

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

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):

Østergaard 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.

Responsible Party:	Director of Clinical Research, 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:	September 8, 2011
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
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Methotrexate
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs

Pharmacologic Actions
Therapeutic Uses
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

ClinicalTrials.gov processed this record on February 09, 2012