A Study of the Safety and Efficacy of Golimumab in Subjects With Active Ankylosing Spondylitis

NCT ID: NCT00265083

Last Updated: 2013-07-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 356 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-12-31
• Study Completion Date: 2012-01-31

Brief Summary

The purpose of this study is to evaluate the safety and efficacy of subcutaneous injections (under the skin) of golimumab for the treatment of active ankylosing spondylitis [AS(arthritis of the spine)]. Efficacy will be measured by reduction in the signs and symptoms of active AS, including effects on back pain and stiffness, physical function, range of motion in the spine, quality of life, and rate of spine damage or fusion on x-ray.

Detailed Description

Anti-tumor necrosis factor (TNF) agents have been shown to be effective treatment for patients with active ankylosing spondylitis (arthritis of the spine) who have not responded to conventional therapy. Golimumab is a new anti-TNFa agent. This is a multicenter, randomized (patients are assigned different treatments based on chance), double-blind (neither the patient nor the physician knows whether drug or placebo is being taken, or at what dosage), placebo-controlled, parallel group study comparing safety and efficacy of golimumab 50mg, golimumab 100mg, and placebo subcutaneous (under the skin) injections administered every 4 weeks, in patients with active AS. The total duration of treatment is approximately 5 years. In the first portion of the study, some patients will be randomly assigned to receive placebo treatment through the Week 20 injection; others will be assigned to golimumab 50mg or golimumab 100mg groups through the Week 20 injection. There is an "early escape" at Week 16 in the study whereby patients who meet criteria for having little improvement in their AS symptoms will be switched to golimumab if they were on placebo, or have the golimumab dose increased if they were originally assigned to the golimumab 50mg group. At Week 24, the placebo group patients will switch to golimumab 50mg injections, and all patients will continue receiving in a blinded manner either 50 or 100mg golimumab injections every 4 weeks until the first 104 weeks of data are fully collected on all the patients (database lock). After this 104-week database lock, everyone will be unblinded to the golimumab dose, and continue to receive golimumab treatment through Week 252 as part of a long-term extension phase of the study, with options for adjusting concomitant AS medications and/or increasing the dose of golimumab. The study hypothesis is that golimumab will be more effective than placebo in treating the signs and symptoms of AS, as measured by the ASsessment in Ankylosing Spondlitis (ASAS) 20 response criteria . Golimumab 50mg, Golimumab 100mg, or placebo injected under the skin every 4 weeks at Weeks 0, 4, 8, 12, 16, and 20, followed by injections of either Golimumab 50mg or Golimumab 100mg every 4 weeks for approximately 5 years total duration from the time of the first study agent injection.

Conditions

Spondylitis, Ankylosing

Study Design

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

Study Groups

003

golimumab 100 mg sc injections every 4 wks from wk 0 up to 5 yrs

Group Type: EXPERIMENTAL

golimumab

Intervention Type: BIOLOGICAL

100 mg sc injections every 4 wks from wk 0 up to 5 yrs

001

Golimumab (CNTO 148); placebo SC injections every 4 wks thru wk 20 (unless early escape at wk 16);golimumab - if early escape, 50mg sc inj every 4wks from wk 16 up to 5yrs ;golimumab -50mg sc injection beginning wk 24 up to 5 yrs (unless early escape); golimumab- Dr's discretion after unblinding, dose adjust from 50 to 100mg

Group Type: PLACEBO_COMPARATOR

Golimumab (CNTO 148); placebo

Intervention Type: BIOLOGICAL

SC injections every 4 wks thru wk 20 (unless early escape at wk 16);golimumab - if early escape, 50mg sc inj every 4wks from wk 16 up to 5yrs ;golimumab -50mg sc injection beginning wk 24 up to 5 yrs (unless early escape); golimumab- Dr's discretion after unblinding, dose adjust from 50 to 100mg

002

golimumab 50 mg sc injs every 4wks from wk 0 thru 5yrs (unless early escape at wk 16); golimumab - If early escape, 100mg sc injections every 4 wks beginning wk 16 up to 5 yrs ; golimumab - Dr's discretion after unblinding, dose adjust from 50 to 100mg

Group Type: EXPERIMENTAL

golimumab

Intervention Type: BIOLOGICAL

50 mg sc injs every 4wks from wk 0 thru 5yrs (unless early escape at wk 16); golimumab - If early escape, 100mg sc injections every 4 wks beginning wk 16 up to 5 yrs ; golimumab - Dr's discretion after unblinding, dose adjust from 50 to 100mg

Interventions

golimumab

100 mg sc injections every 4 wks from wk 0 up to 5 yrs

Intervention Type: BIOLOGICAL

Golimumab (CNTO 148); placebo

SC injections every 4 wks thru wk 20 (unless early escape at wk 16);golimumab - if early escape, 50mg sc inj every 4wks from wk 16 up to 5yrs ;golimumab -50mg sc injection beginning wk 24 up to 5 yrs (unless early escape); golimumab- Dr's discretion after unblinding, dose adjust from 50 to 100mg

Intervention Type: BIOLOGICAL

golimumab

50 mg sc injs every 4wks from wk 0 thru 5yrs (unless early escape at wk 16); golimumab - If early escape, 100mg sc injections every 4 wks beginning wk 16 up to 5 yrs ; golimumab - Dr's discretion after unblinding, dose adjust from 50 to 100mg

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

• Diagnosis of "Definite AS" (arthritis of the spine) as defined by the modified New York criteria, for at least 3 months prior to first dose of study drug
• Symptoms of active disease at screening and at baseline visits, as evidenced by both a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score of >= 4, and a Total Back Pain score of >= 4 (each on a scale of 0 to 10cm)
• Inadequate response to 3 months of continuous therapy with maximal recommended doses of NSAIDs, or else unable to receive a full 3 months of maximal NSAID therapy because of intolerance, toxicity, or contraindications to non-steroidal anti-inflammatory drugs (NSAIDs)
• Stable doses of methotrexate, sulfasalazine, hydroxychloroquine, low-dose corticosteroids, and NSAIDs are permitted.

Exclusion Criteria

• Patients cannot have complete ankylosis of the spine
• No prior treatment with biologic anti-TNF agents (infliximab, etanercept, adalimumab)

• 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

Paradise Valley, Arizona, United States

Los Angeles, California, United States

San Francisco, California, United States

Ormond Beach, Florida, United States

Portland, Oregon, United States

Duncansville, Pennsylvania, United States

Houston, Texas, United States

Edmonds, Washington, United States

Seattle, Washington, United States

Brookfield, Wisconsin, United States

La Crosse, Wisconsin, United States

Brussels, , Belgium

Diepenbeek, , Belgium

Leuven, , Belgium

Edmonton, Alberta, Canada

Vancouver, British Columbia, Canada

Victoria, British Columbia, Canada

Winnipeg, Manitoba, Canada

St. John's, Newfoundland and Labrador, Canada

Toronto, Ontario, Canada

Sainte-Foy, Quebec, Canada

Helsinki, , Finland

Rauma, , Finland

Nantes Cedex 01 N/A, , France

Bad Nauheim, , Germany

Baden-Baden, , Germany

Berlin, , Germany

Erlangen, , Germany

Hanover, , Germany

Herne, , Germany

München, , Germany

Maastricht, , Netherlands

Nijmegen, , Netherlands

Busan, , South Korea

Pusan, , South Korea

Seoul, , South Korea

Kaohsiung City, , Taiwan

Taichung, , Taiwan

Taoyuan District, , Taiwan

Countries

United States; Belgium; Canada; Finland; France; Germany; Netherlands; South Korea; Taiwan

References

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.

Reference Type: DERIVED

PMID: 30412238 (View on PubMed)

Inman RD, Baraliakos X, Hermann KA, Braun J, Deodhar A, van der Heijde D, Xu S, Hsu B. Serum biomarkers and changes in clinical/MRI evidence of golimumab-treated patients with ankylosing spondylitis: results of the randomized, placebo-controlled GO-RAISE study. Arthritis Res Ther. 2016 Dec 28;18(1):304. doi: 10.1186/s13075-016-1200-1.

Reference Type: DERIVED

PMID: 28031053 (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)

Braun J, Baraliakos X, Hermann KG, Xu S, Hsu B. Serum C-reactive Protein Levels Demonstrate Predictive Value for Radiographic and Magnetic Resonance Imaging Outcomes in Patients with Active Ankylosing Spondylitis Treated with Golimumab. J Rheumatol. 2016 Sep;43(9):1704-12. doi: 10.3899/jrheum.160003. Epub 2016 Jul 15.

Reference Type: DERIVED

PMID: 27422890 (View on PubMed)

Braun J, Baraliakos X, Hermann KG, Xu S, Hsu B. Serum Vascular Endothelial Growth Factor Levels Lack Predictive Value in Patients with Active Ankylosing Spondylitis Treated with Golimumab. J Rheumatol. 2016 May;43(5):901-6. doi: 10.3899/jrheum.150897. Epub 2016 Mar 1.

Reference Type: DERIVED

PMID: 26932345 (View on PubMed)

Deodhar A, Braun J, Inman RD, van der Heijde D, Zhou Y, Xu S, Han C, Hsu B. Golimumab administered subcutaneously every 4 weeks in ankylosing spondylitis: 5-year results of the GO-RAISE study. Ann Rheum Dis. 2015 Apr;74(4):757-61. doi: 10.1136/annrheumdis-2014-205862. Epub 2014 Nov 11.

Reference Type: DERIVED

PMID: 25387477 (View on PubMed)

van der Heijde D, Braun J, Deodhar A, Inman RD, Xu S, Mack ME, Hsu B. Comparison of three enthesitis indices in a multicentre, randomized, placebo-controlled trial of golimumab in ankylosing spondylitis (GO-RAISE). Rheumatology (Oxford). 2013 Feb;52(2):321-5. doi: 10.1093/rheumatology/kes251. Epub 2012 Sep 28.

Reference Type: DERIVED

PMID: 23024015 (View on PubMed)

van der Heijde D, Deodhar A, Inman RD, Braun J, Hsu B, Mack M. Comparison of three methods for calculating the Bath Ankylosing Spondylitis Metrology Index in a randomized placebo-controlled study. Arthritis Care Res (Hoboken). 2012 Dec;64(12):1919-22. doi: 10.1002/acr.21771.

Reference Type: DERIVED

PMID: 22740380 (View on PubMed)

Deodhar A, Braun J, Inman RD, Mack M, Parasuraman S, Buchanan J, Hsu B, Gathany T, van der Heijde D. Golimumab reduces sleep disturbance in patients with active ankylosing spondylitis: results from a randomized, placebo-controlled trial. Arthritis Care Res (Hoboken). 2010 Sep;62(9):1266-71. doi: 10.1002/acr.20233.

Reference Type: DERIVED

PMID: 20506403 (View on PubMed)

Other Identifiers

C0524T09

Identifier Type: OTHER

Identifier Source: secondary_id

CR006337

Identifier Type: -

Identifier Source: org_study_id