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

Centocor Ortho Biotech

Status and phase: Completed; Phase 3

Conditions: Spondylitis, Ankylosing

Treatments: Biological: golimumab; Biological: Golimumab (CNTO 148); placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT00265083

CR006337

C0524T09 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 356 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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356 participants in 3 patient groups, including a placebo group

003

Experimental group

Description:

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

Treatment:

Biological: golimumab

Biological: golimumab

001

Placebo Comparator group

Description:

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

Treatment:

Biological: Golimumab (CNTO 148); placebo

002

Experimental group

Description:

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

Treatment:

Biological: golimumab

Biological: golimumab