A Study of Tocilizumab (RoActemra/Actemra) in Patients With Ankylosing Spondylitis Who Have Had an Inadequate Response to Previous Tumor Necrosis Factor (TNF) Antagonist Therapy

This study has been terminated.
(Clinical development program terminated due to failure to achieve efficacy)
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01209689
First received: September 24, 2010
Last updated: December 11, 2012
Last verified: December 2012
  Purpose

This randomized, double-blind, placebo-controlled study evaluated the safety and efficacy of tocilizumab (RoActemra/Actemra) in patients with ankylosing spondylitis (AS) who had an inadequate response to previous tumor necrosis factor (TNF) antagonist therapy. Patients were randomized to receive tocilizumab at a dose of either 8 mg/kg or 4 mg/kg intravenously (iv) or placebo every 4 weeks for 24 weeks. The double-blind treatment period was followed by open-label treatment with tocilizumab 8 mg/kg iv every 4 weeks until Week 104 for all patients.

This study and all further clinical development of tocilizumab AS was halted after a review of 12-week data from Study NA22823, a randomized double-blind, placebo-controlled study in TNF antagonist naïve AS patients, failed to demonstrate efficacy.


Condition Intervention Phase
Spondylitis, Ankylosing
Drug: Tocilizumab
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized, Double-blind, Parallel Group Placebo-controlled Study of the Safety and Reduction of Signs and Symptoms During Treatment With Tocilizumab (TCZ) Versus Placebo in Patients With Ankylosing Spondylitis Who Have Had an Inadequate Response to Previous TNF Antagonist Therapy

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Percentage of ASsessment in Ankylosing Spondylitis 20 (ASAS20) Responders at Week 12 [ Time Frame: Baseline to Week 12 ] [ Designated as safety issue: No ]
    ASAS20 was defined as an improvement of ≥ 20% and an absolute improvement of ≥ 10 units on a 0-100 visual analog scale (VAS) from Baseline to Week 12 in 3 of 4 domains: 1-Patient global assessment (with extremes labelled none and severe), 2-Pain assessment (average total and nocturnal pain scores with extremes labelled no pain and most severe pain), 3-Function (represented by the Bath Ankylosing Spondylitis (BAS) Functional Index [BASFI] average of 10 questions regarding ability to perform specific tasks with extremes labelled easy and impossible), and 4-Inflammation (average of the last 2 questions on the 6-question BAS Disease Activity Index [BASDAI] concerning morning stiffness intensity with extremes labelled none and very severe and duration between 0 and 2 or more hours); and the absence of deterioration (of at least 20% and absolute change of at least 10 units on a 0-100 mm scale) in the remaining domain.


Enrollment: 113
Study Start Date: October 2010
Study Completion Date: December 2011
Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Tocilizumab 4 mg/kg
Patients received tocilizumab 4 mg/kg intravenously every 4 weeks for 24 weeks.
Drug: Tocilizumab
Other Names:
  • RoActemra
  • Actemra
Experimental: Tocilizumab 8 mg/kg
Patients received tocilizumab 8 mg/kg intravenously every 4 weeks for 24 weeks.
Drug: Tocilizumab
Other Names:
  • RoActemra
  • Actemra
Placebo Comparator: Placebo
Patients received placebo to tocilizumab intravenously every 4 weeks for 24 weeks.
Drug: Placebo

  Eligibility

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

Inclusion Criteria:

  • Adult patients ≥ 18 years of age.
  • Ankylosing spondylitis as defined by the modified New York criteria for ≥ 3 months prior to baseline.
  • Active disease at screening and baseline (Bath Ankylosing Spondylitis Disease Activity Index [BASDAI] ≥ 4.0, spinal pain visual analog scale [VAS] ≥ 40).
  • Inadequate response or intolerant to 1 or more previous non-steroidal anti-inflammatory drugs (NSAIDs).
  • Inadequate response to treatment with etanercept, infliximab, adalimumab, or golimumab because of inadequate efficacy.
  • Tumor necrosis factor (TNF) antagonist therapy must have been discontinued at least 8 weeks prior to baseline (etanercept 4 weeks).
  • Traditional disease-modifying anti-rheumatic drugs (DMARDs) must be withdrawn for at least 4 weeks prior to baseline (methotrexate, sulfasalazine, and hydroxychloroquine or chloroquine may be allowed if at stable dose for at least 4 weeks prior to baseline).
  • Oral corticosteroids (≥ 10 mg/day prednisone or equivalent) and NSAIDs/cyclooxygenase-2 [COX-2] inhibitors must be at stable dose for at least 4 weeks prior to baseline.

Exclusion Criteria:

  • Major surgery (including joint surgery) within 8 weeks prior to screening or planned major surgery within 6 months after randomization.
  • Total ankylosis of spine (as determined by investigator).
  • Inflammatory rheumatic disease other than ankylosing spondylitis.
  • Active, acute uveitis at baseline.
  • Previous treatment with tocilizumab.
  • Intra-articular or tendon injections or parenteral corticosteroids within 4 weeks prior to screening.
  • History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies.
  • Active current or history of recurrent bacterial, viral, fungal, mycobacterial, or other infection.
  • History of or currently active primary or secondary immunodeficiency.
  • Body weight > 150 kg.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01209689

  Show 140 Study Locations
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

No publications provided by Hoffmann-La Roche

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01209689     History of Changes
Other Study ID Numbers: WA22908, 2009-017488-40
Study First Received: September 24, 2010
Results First Received: December 11, 2012
Last Updated: December 11, 2012
Health Authority: United States: Food and Drug Administration

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 24, 2014