A Study of the Safety and Efficacy of Golimumab (CNTO 148) in Subjects With Active Rheumatoid Arthritis Previously Treated With Biologic Anti-TNFa Agent(s)

NCT ID: NCT00299546

Last Updated: 2014-02-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 461 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-02-28
• Study Completion Date: 2012-05-31

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of golimumab (CNTO 148) in subjects who have active rheumatoid arthritis and have been treated previously with at least 1 dose of a biologic anti-TNFa agent (etanercept, adalimumab or infliximab).

Detailed Description

Golimumab is a fully human protein (antibody) which binds to tumor necrosis factor-alpha (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 in subjects with active RA previously treated with at least 1 dose of a biologic anti-TNFa agent (etanercept, adalimumab or infliximab). Concomitant therapy with methotrexate, sulfasalazine and/or hydroxychloroquine is permitted if the subject has tolerated these medications for at least 12 weeks prior to the first administration of study drug and is on a stable dose for at least 4 weeks prior to the first administration of study agent. The study hypothesis is that golimumab will be a safe and effective treatment for RA in subjects with active RA previously treated with at least one biologic anti-TNFa agent as measured by the American College of Rheumatology (ACR) response criteria, the Disease Activity Score 28 (DAS28) responses and the change from baseline in Health Assessment Questionnaire (HAQ), without causing unacceptable significant adverse effects. The ACR response criteria were designed to assess the level of improvement in the signs and symptoms of RA. The DAS28 responses also measure improvement in the signs and symptoms of RA using the joint examination and laboratory testing. The HAQ is a series of questions that measure a subject's impairment in physical function caused by RA. Patients will receive golimumab 50 mg or 100 mg or placebo injections under the skin every 4 weeks until Week 24. After Week 24, all subjects receive golimumab 50 mg or 100 mg injections, and golimumab continues for all groups every 4 weeks for about 4 and a half more years.

Conditions

Arthritis, Rheumatoid

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Group 1: Placebo

Placebo Subcutaneous (SC) injections every 4 weeks (wks) thru Wk 20 (unless early escape at Wk 16); Golimumab - if early escape, 50 mg SC injections from Wk 16 up to 5 yrs; Golimumab - 50 mg SC injections beginning Wk 24 up to 5 yrs (unless early escape); 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-24 database lock.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

SC injections

Golimumab 50 mg

Intervention Type: BIOLOGICAL

SC injections

Group 2: Golimumab 50 mg

Golimumab 50 mg SC injections every 4 wks from Wk 0 up to 5 yrs (unless early escape at Wk 16); Golimumab - if early escape, 100 mg SC injections every 4 wks beginning Wk 16 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-24 database lock.

Group Type: EXPERIMENTAL

Golimumab 50 mg

Intervention Type: BIOLOGICAL

SC injections

Group 3: Golimumab 100 mg

Golimumab 100 mg SC injections every 4 wks from Wk 0 up to 5 yrs; Golimumab - Dr's discretion after unblinding, dose adjusted from 100 to 50 mg. Duration of the blinded period will be until the week-24 database lock.

Group Type: EXPERIMENTAL

Golimumab 100 mg

Intervention Type: BIOLOGICAL

SC injections

Interventions

Placebo

SC injections

Intervention Type: DRUG

Golimumab 50 mg

SC injections

Intervention Type: BIOLOGICAL

Golimumab 100 mg

SC injections

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

• Patients have a diagnosis of rheumatoid arthritis (RA) (according to the revised 1987 criteria of the ACR) for at least 3 months 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
• Must have been previously treated with at least one dose of etanercept, adalimumab, or infliximab
• If currently using methotrexate, sulfasalazine and/or hydroxychloroquine must have tolerated these agents for at least 12 weeks and be on a stable dose for at least 4 weeks prior to the first administration of study agent
• If using NSAIDs or other analgesics must be on a stable dose for at least 2 weeks prior to the first administration of study agent
• 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

• Patients cannot have other inflammatory diseases other than RA that might interfere with the evaluation of the benefit of golimumab therapy
• No history of treatment with natalizumab, rituximab or cytotoxic agents
• No history of demyelinating diseases such as multiple sclerosis or optic neuritis or of concurrent congestive heart failure (CHF), lymphoproliferative disease, known malignancy or history of malignancy within the previous 5 years (with the exception of a nonmelanoma skin cancer that has been treated with no evidence of recurrence)
• No history of, or ongoing, chronic or recurrent infectious disease
• No serious infection within 2 months prior to first administration of study agent.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Schering-Plough

INDUSTRY

Sponsor Role: collaborator

Centocor, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Centocor, Inc. Clinical Trial

Role: STUDY_DIRECTOR

Centocor, Inc.

Locations

Birmingham, Alabama, United States

Huntsville, Alabama, United States

Paradise Valley, Arizona, United States

La Jolla, California, United States

Los Angeles, California, United States

Santa Monica, California, United States

Torrance, California, United States

Upland, California, United States

Trumbull, Connecticut, United States

Aventura, Florida, United States

Jacksonville, Florida, United States

Jupiter, Florida, United States

Largo, Florida, United States

Palm Harbor, Florida, United States

Tamarac, Florida, United States

Moline, Illinois, United States

Springfield, Illinois, United States

Cedar Rapids, Iowa, United States

Witchita, Kansas, United States

Louisville, Kentucky, United States

Wheaton, Maryland, United States

Boston, Massachusetts, United States

Rochester, Minnesota, United States

St Louis, Missouri, United States

Syracuse, New York, United States

Charlotte, North Carolina, United States

Wilmington, North Carolina, United States

Cincinnati, Ohio, United States

Mayfield, Ohio, United States

Duncansville, Pennsylvania, United States

Pittsburgh, Pennsylvania, United States

West Reading, Pennsylvania, United States

Knoxville, Tennessee, United States

Fort Worth, Texas, United States

Houston, Texas, United States

Lubbock, Texas, United States

Arlington, Virginia, United States

Spokane, Washington, United States

Brookfield, Wisconsin, United States

Racine, Wisconsin, United States

Adelaide, , Australia

Cotton Tree, , Australia

Melbourne, , Australia

Graz, , Austria

Lainz/Wien N/A, , Austria

Vienna, , Austria

Victoria, British Columbia, Canada

Winnipeg, Manitoba, Canada

St. John's, Newfoundland and Labrador, Canada

Kitchener, Ontario, Canada

Newmarket, Ontario, Canada

Ottawa, Ontario, Canada

Toronto, Ontario, Canada

Sainte-Foy, Quebec, Canada

Claire, , Canada

Helsinki, , Finland

Hyvinkää, , Finland

Jyvalskyla, , Finland

Baden-Baden, , Germany

Berlin, , Germany

Cologne, , Germany

Erlangen, , Germany

Hamburg, , Germany

Herne, , Germany

München, , Germany

Vogelsang-Gommern, , Germany

Würzburg, , Germany

Maastricht, , Netherlands

Auckland, , New Zealand

Rotorua, , New Zealand

Timaru, , New Zealand

Santander, , Spain

Seville, , Spain

Valencia, , Spain

Leeds, , United Kingdom

London, , United Kingdom

Oxford, , United Kingdom

Countries

United States; Australia; Austria; Canada; Finland; Germany; Netherlands; New Zealand; Spain; United Kingdom

References

Vieira MC, Zwillich SH, Jansen JP, Smiechowski B, Spurden D, Wallenstein GV. Tofacitinib Versus Biologic Treatments in Patients With Active Rheumatoid Arthritis Who Have Had an Inadequate Response to Tumor Necrosis Factor Inhibitors: Results From a Network Meta-analysis. Clin Ther. 2016 Dec;38(12):2628-2641.e5. doi: 10.1016/j.clinthera.2016.11.004. Epub 2016 Nov 24.

Reference Type: DERIVED

PMID: 27889300 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 27803138 (View on PubMed)

Smolen JS, Kay J, Doyle M, Landewe R, Matteson EL, Gaylis N, Wollenhaupt J, Murphy FT, Xu S, Zhou Y, Hsia EC. Golimumab in patients with active rheumatoid arthritis after treatment with tumor necrosis factor alpha inhibitors: findings with up to five years of treatment in the multicenter, randomized, double-blind, placebo-controlled, phase 3 GO-AFTER study. Arthritis Res Ther. 2015 Jan 22;17(1):14. doi: 10.1186/s13075-015-0516-6.

Reference Type: DERIVED

PMID: 25627338 (View on PubMed)

Smolen JS, Kay J, Doyle MK, Landewe R, Matteson EL, Wollenhaupt J, Gaylis N, Murphy FT, Neal JS, Zhou Y, Visvanathan S, Hsia EC, Rahman MU; GO-AFTER study investigators. Golimumab in patients with active rheumatoid arthritis after treatment with tumour necrosis factor alpha inhibitors (GO-AFTER study): a multicentre, randomised, double-blind, placebo-controlled, phase III trial. Lancet. 2009 Jul 18;374(9685):210-21. doi: 10.1016/S0140-6736(09)60506-7. Epub 2009 Jun 26.

Reference Type: DERIVED

PMID: 19560810 (View on PubMed)

Other Identifiers

C0524T11

Identifier Type: OTHER

Identifier Source: secondary_id

CR006334

Identifier Type: -

Identifier Source: org_study_id