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

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

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.

Study Overview

• Status: Terminated
• Conditions: Spondylitis, Ankylosing
• Intervention / Treatment: Drug: Placebo; Drug: Tocilizumab

• Study Type: Interventional
• Enrollment (Actual): 113
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Heidelberg, Australia, 3084
  • Hobart, Australia, 7000
  • Sydney, Australia, 2050
  • Woodville, Australia, 5011
• Belgium
  • Bruxelles, Belgium, 1200
  • Gent, Belgium, 9000
  • Kortrijk, Belgium, 8500
  • Liege, Belgium, 4000
  • Yvoir, Belgium, 5530
• Brazil
  • Cuiabá, Brazil, 78025-000
  • Goiania, Brazil, 74110-120
  • Sao Paulo, Brazil, 04039-000
  • Sao Paulo, Brazil, 04026-000
  • São Paulo, Brazil, 04266-010
• Bulgaria
  • Plovdiv, Bulgaria, 4002
  • Plovdiv, Bulgaria, 4003
  • Sofia, Bulgaria, 1233
  • Sofia, Bulgaria, 1606
  • Sofia, Bulgaria, 1612
• Canada
  • St. John's, Canada, A1C 5B8
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N1
  • Ontario
    • Hamilton, Ontario, Canada, L8N 1Y2
    • Kitchener, Ontario, Canada, N2M 5N6
    • Mississauga, Ontario, Canada, L5M 2V8
    • St. Catharines, Ontario, Canada, L2N 7E4
    • Toronto, Ontario, Canada, M5T 2S8
    • Toronto, Ontario, Canada, M9W 6V1
  • Quebec
    • Montreal, Quebec, Canada, H1T 2M4
    • Quebec City, Quebec, Canada, G1V 3M7
    • Trois-rivières, Quebec, Canada, G8Z 1Y2
• Czech Republic
  • Bruntal, Czech Republic, 792 01
  • Hlucin, Czech Republic, 748 01
  • Olomouc, Czech Republic, 775 20
  • Prague, Czech Republic, 12850
  • Uherske Hradiste, Czech Republic, 686 01
  • Zlin, Czech Republic, 760 01
• Denmark
  • Esbjerg, Denmark, 6700
  • Hellerup, Denmark, 2900
  • Vejle, Denmark, 7100
• France
  • Besancon, France, 25030
  • Bordeaux, France, 33076
  • Boulogne-billancourt, France, 92104
  • Creteil, France, 94010
  • Grenoble, France, 38042
  • Le Kremlin Bicetre, France, 94275
  • Lyon Cedex 3, France, 69437
  • Montpellier, France, 34295
  • Orléans Cedex 2, France, 45067
  • Paris, France, 75571
  • Paris, France, 75679
  • Rouen Cedex, France, 76031
  • Strasbourg, France, 67098
  • Vandoeuvre-les-nancy, France, 54511
• Germany
  • Berlin, Germany, 10117
  • Berlin, Germany, 14059
  • Erlangen, Germany, 91054
  • Frankfurt, Germany, 60590
  • Gommern, Germany, 39245
  • Hamburg, Germany, 22081
  • Hannover, Germany, 30625
  • Heidelberg, Germany, 69120
  • Herne, Germany, 44652
  • Köln, Germany, 50924
  • München, Germany, 80336
  • Regensburg, Germany, 93053
  • Rostock, Germany, 18059
  • Tuebingen, Germany, 72076
  • Würzburg, Germany, 97080
• India
  • Bangalore, India, 560034
  • Bangalore, India, 560076
  • Jaipur, India, 302 015
  • New Delhi, India, 110029
  • Secunderabad, India, 500003
• Italy
  • Ferrara, Italy, 44100
  • Firenze, Italy, 50141
  • Monserrato, Italy, 09042
  • Padova, Italy, 35128
  • Pisa, Italy, 56126
  • Prato, Italy, 59100
  • Reggio Emilia, Italy, 42100
  • Roma, Italy, 00161
  • Siena, Italy, 53100
• Lithuania
  • Kaunas, Lithuania, 50009
  • Klaipeda, Lithuania, 92288
• Netherlands
  • Amsterdam, Netherlands, 1105 AZ
  • Amsterdam, Netherlands, 1081 HV
  • Amsterdam, Netherlands, 1056 AB
• Poland
  • Bydgoszcz, Poland, 85-168
  • Krakow, Poland, 31-121
  • Lublin, Poland, 20-954
  • Poznan, Poland, 60-218
  • Torun, Poland, 87-100
  • Warszawa, Poland, 00-909
  • Wroclaw, Poland, 51-124
• Slovakia
  • Kosice, Slovakia, 040 66
  • Piestany, Slovakia, 921 01
• South Africa
  • Cape Town, South Africa, 7500
  • Cape Town, South Africa, 8001
  • Durban, South Africa, 4001
  • Pinelands, South Africa, 7405
  • Pretoria, South Africa, 0002
  • Stellenbosch, South Africa, 7600
• Spain
  • Alcorcon, Spain, 28922
  • Barcelona, Spain, 08036
  • Córdoba, Spain, 14004
  • La Coruna, Spain, 15006
  • Lugo, Spain, 27004
  • Madrid, Spain, 28046
  • Madrid, Spain, 28222
  • Madrid, Spain, 28009
  • Oviedo, Spain, 33006
  • Oviedo, Spain, 33012
  • Sabadell, Spain, 08208
• United Kingdom
  • Basingstoke, United Kingdom, RG24 9NA
  • Bath, United Kingdom, BA1 1RL
  • Greenock, United Kingdom, PA16 0XN
  • Leeds, United Kingdom, LS7 4SA
  • London, United Kingdom, EC1M 6BQ
  • Salford, United Kingdom, M6 8HD
  • Stoke-on-trent, United Kingdom, ST6 7AG
  • Wigan, United Kingdom, WN6 9EW
• United States
  • California
    • Huntington Beach, California, United States, 92646
  • Florida
    • Aventura, Florida, United States, 33180
    • Miami, Florida, United States, 33169
    • Orlando, Florida, United States, 32804
    • Tampa, Florida, United States, 33609
  • Georgia
    • Atlanta, Georgia, United States, 30342
    • Decatur, Georgia, United States, 30033
    • Marietta, Georgia, United States, 30060
  • Idaho
    • Idaho Falls, Idaho, United States, 83404
  • Kansas
    • Wichita, Kansas, United States, 67207
  • Maryland
    • Hagerstown, Maryland, United States, 21740
  • Michigan
    • St. Claire Shores, Michigan, United States, 48081
  • New Jersey
    • Freehold, New Jersey, United States, 07728
  • North Carolina
    • Asheville, North Carolina, United States, 28803
    • Charlotte, North Carolina, United States, 28210
    • Greensboro, North Carolina, United States, 27408
  • Pennsylvania
    • Duncansville, Pennsylvania, United States, 16635
  • Texas
    • Austin, Texas, United States, 78731
    • Houston, Texas, United States, 77004

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of ASsessment in Ankylosing Spondylitis 20 (ASAS20) Responders at Week 12	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.	Baseline to Week 12

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Publications and helpful links

General Publications

• Sieper J, Porter-Brown B, Thompson L, Harari O, Dougados M. Assessment of short-term symptomatic efficacy of tocilizumab in ankylosing spondylitis: results of randomised, placebo-controlled trials. Ann Rheum Dis. 2014 Jan;73(1):95-100. doi: 10.1136/annrheumdis-2013-203559. Epub 2013 Jun 13.

Study record dates

Study Major Dates

• Study Start: October 1, 2010
• Primary Completion (Actual): December 1, 2011
• Study Completion (Actual): December 1, 2011

Study Registration Dates

• First Submitted: September 24, 2010
• First Submitted That Met QC Criteria: September 24, 2010
• First Posted (Estimate): September 27, 2010

Study Record Updates

• Last Update Posted (Estimate): January 17, 2013
• Last Update Submitted That Met QC Criteria: December 11, 2012
• Last Verified: December 1, 2012

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Joint Diseases; Musculoskeletal Diseases; Arthritis; Spinal Diseases; Bone Diseases; Spondylarthropathies; Bone Diseases, Infectious; Ankylosis; Spondylitis; Spondylarthritis; Spondylitis, Ankylosing
• Other Study ID Numbers: WA22908; 2009-017488-40