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

This study has been completed.
Sponsor:
Collaborator:
Schering-Plough
Information provided by (Responsible Party):
Centocor, Inc.
ClinicalTrials.gov Identifier:
NCT00265083
First received: December 12, 2005
Last updated: July 12, 2013
Last verified: July 2013
  Purpose

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.


Condition Intervention Phase
Spondylitis, Ankylosing
Biological: golimumab
Biological: Golimumab (CNTO 148); placebo
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-controlled Trial of Golimumab, a Fully Human Anti-TNFalpha MonoclonalAntibody, Administered Subcutaneously, in Subjects With Active Ankylosing Spondylitis

Resource links provided by NLM:


Further study details as provided by Centocor, Inc.:

Primary Outcome Measures:
  • Assessment in Ankylosing Spondylitis 20 Responders at Week 14 [ Time Frame: Week 14 ] [ Designated as safety issue: No ]
    Number of patients who achieved a 20% improvement and at least 1 absolute improvement on a 0 to 10 cm scale from baseline to Week 14 in at least 3 of the 4 domains: patient global, total back pain, function or inflammation.


Secondary Outcome Measures:
  • Assessment in Ankylosing Spondylitis 20 Responders at Week 24 [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    Number of patients who achieved a 20% improvement and at least 1 absolute improvement on a 0 to 10 cm scale from baseline to Week 24 at least 3 of the 4 domains: patient global, total back pain, function or inflammation.

  • Summary of Change From Baseline in Bath Ankylosing Spondylitis Functional Index at Week 14 [ Time Frame: From Baseline to Week 14 ] [ Designated as safety issue: No ]
    The Bath Ankylosing Spondylitis Functional Index (BASFI) is calculated as the mean of 10 VAS, each of length 0 to 10 cm. Eight of the scales relate to functional capacity of patients while the other 2 relate to a patient's ability to cope with everyday life. Change from baseline is Wk 14 value minus baseline value.

  • Summary of Change From Baseline in Bath Ankylosing Spondylitis Metrology Index at Week 14 [ Time Frame: From Baseline to Week 14 ] [ Designated as safety issue: No ]
    The Bath Ankylosing Spondylitis Metrology Index (BASMI) is the sum of scores comprised of 5 measures (0=mild, 1=moderate & 2=severe): Tragus-to-wall; Lumbar flexion; Cervical rotation; Lumbar side flexion; Intermalleolar distance. BASMI ranges from 0 to 10. Change from baseline is Wk 14 value minus baseline value.


Enrollment: 356
Study Start Date: December 2005
Study Completion Date: January 2012
Primary Completion Date: March 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 003
golimumab 100 mg sc injections every 4 wks from wk 0 up to 5 yrs
Biological: golimumab
100 mg sc injections every 4 wks from wk 0 up to 5 yrs
Placebo Comparator: 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
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
Experimental: 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
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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)
  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: NCT00265083

  Show 39 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: NCT00265083     History of Changes
Other Study ID Numbers: CR006337, C0524T09
Study First Received: December 12, 2005
Results First Received: May 21, 2009
Last Updated: July 12, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Centocor, Inc.:
Spondylitis
subcutaneous injection
Bechterew's Disease
Spondyloarthritis
Spondyloarthropathy

Additional relevant MeSH terms:
Spondylitis
Spondylitis, Ankylosing
Bone Diseases, Infectious
Infection
Bone Diseases
Musculoskeletal Diseases
Spinal Diseases
Spondylarthropathies
Spondylarthritis
Ankylosis
Joint Diseases
Arthritis

ClinicalTrials.gov processed this record on July 28, 2014