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

NCT01209689 | Terminated Phase 3 Results

• 2 other identifiers: WA229082009-017488-40
• Study Type: interventional
• Target: 113
• Locations: 19 countries
• Sites: 140

Brief Summary

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.

Conditions

Spondylitis, Ankylosing

Outcome Measures

Primary Outcomes (1)

• 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

Study Arms (3)

Tocilizumab 4 mg/kg

EXPERIMENTAL

Patients received tocilizumab 4 mg/kg intravenously every 4 weeks for 24 weeks.

Drug: Tocilizumab

Tocilizumab 8 mg/kg

EXPERIMENTAL

Patients received tocilizumab 8 mg/kg intravenously every 4 weeks for 24 weeks.

Drug: Tocilizumab

Placebo

PLACEBO COMPARATOR

Patients received placebo to tocilizumab intravenously every 4 weeks for 24 weeks.

Drug: Placebo

Interventions

Tocilizumab DRUG

Also known as: RoActemra, Actemra

Tocilizumab 4 mg/kg; Tocilizumab 8 mg/kg

Placebo DRUG

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (140)

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Huntington Beach, California, 92646, United States

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Aventura, Florida, 33180, United States

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Miami, Florida, 33169, United States

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Orlando, Florida, 32804, United States

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Tampa, Florida, 33609, United States

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Atlanta, Georgia, 30342, United States

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Decatur, Georgia, 30033, United States

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Marietta, Georgia, 30060, United States

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Idaho Falls, Idaho, 83404, United States

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Wichita, Kansas, 67207, United States

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Hagerstown, Maryland, 21740, United States

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Saint Claire Shores, Michigan, 48081, United States

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Freehold, New Jersey, 07728, United States

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Asheville, North Carolina, 28803, United States

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Charlotte, North Carolina, 28210, United States

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Greensboro, North Carolina, 27408, United States

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Duncansville, Pennsylvania, 16635, United States

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Austin, Texas, 78731, United States

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Houston, Texas, 77004, United States

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Heidelberg, 3084, Australia

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Hobart, 7000, Australia

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Sydney, 2050, Australia

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Woodville, 5011, Australia

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Brussels, 1200, Belgium

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Ghent, 9000, Belgium

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Kortrijk, 8500, Belgium

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Liège, 4000, Belgium

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Yvoir, 5530, Belgium

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Cuiabá, 78025-000, Brazil

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Goiânia, 74110-120, Brazil

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São Paulo, 04026-000, Brazil

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São Paulo, 04039-000, Brazil

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São Paulo, 04266-010, Brazil

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Plovdiv, 4002, Bulgaria

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Plovdiv, 4003, Bulgaria

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Sofia, 1233, Bulgaria

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Sofia, 1606, Bulgaria

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Sofia, 1612, Bulgaria

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Calgary, Alberta, T2N 4N1, Canada

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Hamilton, Ontario, L8N 1Y2, Canada

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Kitchener, Ontario, N2M 5N6, Canada

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Mississauga, Ontario, L5M 2V8, Canada

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St. Catharines, Ontario, L2N 7E4, Canada

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Toronto, Ontario, M5T 2S8, Canada

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Toronto, Ontario, M9W 6V1, Canada

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Montreal, Quebec, H1T 2M4, Canada

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Québec, Quebec, G1V 3M7, Canada

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Trois-Rivières, Quebec, G8Z 1Y2, Canada

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St. John's, A1C 5B8, Canada

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Bruntál, 792 01, Czechia

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Hlučín, 748 01, Czechia

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Olomouc, 775 20, Czechia

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Prague, 12850, Czechia

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Uherské Hradiště, 686 01, Czechia

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Zlín, 760 01, Czechia

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Esbjerg, 6700, Denmark

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Hellerup, 2900, Denmark

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Vejle, 7100, Denmark

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Besançon, 25030, France

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Bordeaux, 33076, France

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Boulogne-Billancourt, 92104, France

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Créteil, 94010, France

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Grenoble, 38042, France

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Le Kremlin-Bicêtre, 94275, France

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Lyon, 69437, France

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Montpellier, 34295, France

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Orléans, 45067, France

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Paris, 75571, France

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Paris, 75679, France

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Rouen, 76031, France

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Strasbourg, 67098, France

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Vandœuvre-lès-Nancy, 54511, France

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Berlin, 10117, Germany

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Berlin, 14059, Germany

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Cologne, 50924, Germany

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Erlangen, 91054, Germany

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Frankfurt, 60590, Germany

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Gommern, 39245, Germany

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Hamburg, 22081, Germany

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Hanover, 30625, Germany

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Heidelberg, 69120, Germany

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Herne, 44652, Germany

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München, 80336, Germany

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Regensburg, 93053, Germany

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Rostock, 18059, Germany

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Tübingen, 72076, Germany

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Würzburg, 97080, Germany

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Bangalore, 560034, India

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Bangalore, 560076, India

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Jaipur, 302 015, India

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New Delhi, 110029, India

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Secunderabad, 500003, India

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Ferrara, 44100, Italy

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Florence, 50141, Italy

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Monserrato, 09042, Italy

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Padua, 35128, Italy

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Pisa, 56126, Italy

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Prato, 59100, Italy

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Reggio Emilia, 42100, Italy

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Roma, 00161, Italy

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Siena, 53100, Italy

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Kaunas, 50009, Lithuania

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Klaipėda, 92288, Lithuania

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Amsterdam, 1056 AB, Netherlands

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Amsterdam, 1081 HV, Netherlands

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Amsterdam, 1105 AZ, Netherlands

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Bydgoszcz, 85-168, Poland

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Krakow, 31-121, Poland

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Lublin, 20-954, Poland

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Poznan, 60-218, Poland

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Torun, 87-100, Poland

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Warsaw, 00-909, Poland

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Wroclaw, 51-124, Poland

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Košice, 040 66, Slovakia

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Piešťany, 921 01, Slovakia

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Cape Town, 7500, South Africa

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Cape Town, 8001, South Africa

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Durban, 4001, South Africa

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Pinelands, 7405, South Africa

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Pretoria, 0002, South Africa

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Stellenbosch, 7600, South Africa

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A Coruña, 15006, Spain

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Alcorcón, 28922, Spain

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Barcelona, 08036, Spain

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Córdoba, 14004, Spain

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Lugo, 27004, Spain

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Madrid, 28009, Spain

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Madrid, 28046, Spain

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Madrid, 28222, Spain

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Oviedo, 33006, Spain

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Oviedo, 33012, Spain

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Sabadell, 08208, Spain

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Basingstoke, RG24 9NA, United Kingdom

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Bath, BA1 1RL, United Kingdom

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Greenock, PA16 0XN, United Kingdom

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Leeds, LS7 4SA, United Kingdom

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London, EC1M 6BQ, United Kingdom

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Salford, M6 8HD, United Kingdom

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Stoke-on-Trent, ST6 7AG, United Kingdom

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Wigan, WN6 9EW, United Kingdom

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Related Publications (1)

• 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.

  PMID: 23765873 DERIVED

MeSH Terms

Conditions

Spondylitis, Ankylosing

Interventions

tocilizumab

Condition Hierarchy (Ancestors)

Axial Spondyloarthritis; Spondylarthropathies; Spondylarthritis; Spondylitis; Spinal Diseases; Bone Diseases; Musculoskeletal Diseases; Ankylosis; Joint Diseases; Arthritis

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

800 821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 24, 2010
• First Posted: September 27, 2010
• Study Start: October 1, 2010
• Primary Completion: December 1, 2011
• Study Completion: December 1, 2011
• Last Updated: January 17, 2013
• Results First Posted: January 17, 2013

Record last verified: 2012-12

Locations

AU (4); BR (5); BU (5); IN (5); NL (3); SL (2); BE (5); ES (11); US (19); FR (14); DK (3); ZA (6); GB (8); DE (15); PL (7); LI (2); CA (11); CZ (6); IT (9)