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A Study of RoActemra/Actemra (Tocilizumab) in Patients With Ankylosing Spondylitis Who Have Failed Treatment With NSAIDs

Information source: Hoffmann-La Roche
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Spondylitis, Ankylosing

Intervention: tocilizumab (Biological); Placebo (Drug)

Phase: Phase 3

Status: Terminated

Sponsored by: Hoffmann-La Roche

Official(s) and/or principal investigator(s):
Clinical Trials, Study Director, Affiliation: Hoffmann-La Roche


This randomized, double-blind, placebo-controlled study will evaluate the safety and efficacy of RoActemra/Actemra (tocilizumab) in patients with ankylosing spondylitis (AS) who have failed treatment with non-steroidal anti-inflammatory drugs and are nave to tumor necrsos factor (TNF) antagonist therapy. In Part 1 of the study, patients will be randomized to receive either RoActemra/Actemra 8 mg/kg intravenously (IV) or placebo every 4 weeks for 12 weeks. In Part 2, patients will be randomized to receive RoActemra at either 8 mg/kg or 4 mg/kg IV or placebo every 4 weeks for 24 weeks. The double-blind treatment period will be followed by open-label treatment with RoActemra/Actemra 8 mg/kg iv every 4 weeks until Week 208 for all patients. Anticipated time on study treatment is 208 weeks.

Clinical Details

Official title: A Ph II/III Seamless, Multi-center, Randomized, Double-blind, Placebo-controlled Study of the Reduction in Signs and Symptoms and Inhibition of Structural Damage During Treatment With Tocilizumab Versus Placebo in Patients With Ankylosing Spondylitis Who Have Failed Non-steroidal Anti-inflammatory Drugs and Are nave to TNF Antagonist Therapy NSAIDs

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Primary outcome:

Part 1: Percentage of Participants Achieving a 20% Improvement in Assessment in Ankylosing Spondylitis (ASAS20) at Week 12

Part 2: Percentage of Participants Achieving a 20% Improvement in Assessment in Ankylosing Spondylitis (ASAS20) at Week 12

Secondary outcome:

Part 2: Percentage of Participants Achieving a 20% Improvement in Assessment in Ankylosing Spondylitis (ASAS20) at Week 24

Percentage of Participants Who Achieved a Value <2 in Each of the 4 ASAS Parameters at Week 12

Percentage of Participants Achieving a 40% Improvement in Assessment in Ankylosing Spondylitis (ASAS40) at Week 12

Part 2: Percentage of Participants Achieving a 40% Improvement in Assessment in Ankylosing Spondylitis (ASAS40) at Week 24

Change From Baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)

Change From Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI)

Change From Baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI)

Change From Baseline in C-Reactive Protein

Part 2: Area Under the Plasma Concentration Versus Time Curve of Tocilizumab

Part 2: Peak Plasma Concentration of Tocilizumab

Part 2: Elimination Half-life of Tocilizumab

Part 2: Clearance of Tocilizumab

Part 2: Volume of Distribution of Tocilizumab

Change From Baseline in the Level of Interleukin-6

Change From Baseline in Level of Soluble Interleukin-6 Receptor

Number of Participants With Anti-tocilizumab Antibodies

Part 2: Radiographic Change According to the Modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS)

Part 2: Percentage of Participants With a Reduction of Magnetic Resonance Imaging (MRI) Proven Spinal Inflammation

Part 1: The Number of Participants With Adverse Events

Detailed description: This study was planned as a Phase II/III seamless, multicenter, randomized, double-blind, placebo-controlled study in patients with AS who were naïve to TNF antagonist therapy. The study consisted of 2 parts, each preceded by a screening visit and followed by a common open-label extension phase. Recruitment into Part 2 commenced after completion of enrollment for Part 1. Part 1 was designed as a Phase II study exploring the efficacy and safety of tocilizumab therapy versus placebo. Part 1 was intended to determine whether Part 2 of the study would continue, based on a Week 12 analysis. Part 2 was designed to provide pivotal Phase III efficacy and safety data for tocilizumab in patients with AS. Approximately 400 patients were to be enrolled. Once randomization into Part 1 was complete, randomization into Part 2 of the study was to be initiated. Based on the results of the Week 12 Part 1 analyses of the primary endpoint (ASAS20) and secondary endpoints, and in consideration of all available safety data, a benefit/risk assessment was made and it was decided to halt the study because of lack of overall efficacy. Most patients did not complete the 24-week double-blind treatment period in Part 2.


Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.


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)

- 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/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

- Treatment with tumor necrosis factor (TNF) antagonist therapy at any time prior to


- 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

Locations and Contacts

Adelaide 5041, Australia

Heidelberg 3084, Australia

Hobart 7000, Australia

Malvern East 3145, Australia

Maroochydore 4558, Australia

Sydney 2050, Australia

Woodville 5011, Australia

Bruxelles 1200, Belgium

Kortrijk 8500, Belgium

Liege 4000, Belgium

Yvoir 5530, Belgium

Cuiabá 78025-000, Brazil

Goiania 74110-120, Brazil

Sao Paulo 04039-000, Brazil

Sao Paulo 04026-000, Brazil

São Paulo 04266-010, Brazil

Plovdiv 4002, Bulgaria

Plovdiv 4003, Bulgaria

Ruse 7002, Bulgaria

Sevlievo 5400, Bulgaria

Sofia 1709, Bulgaria

Sofia 1606, Bulgaria

Sofia 1612, Bulgaria

Sofia 1233, Bulgaria

Bruntal 792 01, Czech Republic

Hlucin 748 01, Czech Republic

Olomouc 775 20, Czech Republic

Prague 12850, Czech Republic

Praha 11 148 00, Czech Republic

Praha 4 Nusle 140 00, Czech Republic

Praha 4 140 00, Czech Republic

Sokolov 356 01, Czech Republic

Uherske Hradiste 686 01, Czech Republic

Zlin 760 01, Czech Republic

Besancon 25030, France

Boulogne-billancourt 92104, France

Creteil 94010, France

Grenoble 38042, France

Montpellier 34295, France

Paris 75679, France

Strasbourg 67098, France

Toulouse 31059, France

Berlin 10117, Germany

Berlin 14059, Germany

Gommern 39245, Germany

Hannover 30625, Germany

Köln 50924, Germany

Würzburg 97080, Germany

Ahmedabad 380009, India

Bangalore 560054, India

Bangalore 560034, India

Bangalore 560076, India

Bangalore 560003, India

Hyderabad 500 033, India

Jaipur 302 015, India

New Delhi 110076, India

New Delhi 110029, India

Secunderabad 500003, India

Ferrara 44100, Italy

Firenze 50141, Italy

Monserrato 09042, Italy

Prato 59100, Italy

Reggio Emilia 42100, Italy

Roma 00161, Italy

Siena 53100, Italy

Kaunas 50009, Lithuania

Klaipeda 92288, Lithuania

Vilnius LT-08661, Lithuania

Bydgoszcz 85-168, Poland

Krakow 31-121, Poland

Krakow 30-119, Poland

Lublin 20-607, Poland

Lublin 20-954, Poland

Poznan 60-218, Poland

Torun 87-100, Poland

Warszawa 02-256, Poland

Warszawa 00-909, Poland

Warszawa 00-235, Poland

Wroclaw 51-124, Poland

Kazan 4420029, Russian Federation

Moscow 115522, Russian Federation

Moscow 123060, Russian Federation

Voronezh 394066, Russian Federation

Yaroslavl 150062, Russian Federation

Kosice 040 66, Slovakia

Piestany 921 01, Slovakia

Cape Town 8001, South Africa

Cape Town 7405, South Africa

Cape Town 7500, South Africa

Durban 4001, South Africa

Pretoria 0084, South Africa

Pretoria 0184, South Africa

Pretoria 0002, South Africa

Stellenbosch 7600, South Africa

Barcelona 08036, Spain

Córdoba 14004, Spain

La Coruna 15006, Spain

Lugo 27004, Spain

Madrid 28009, Spain

Madrid 28046, Spain

Madrid 28222, Spain

Oviedo 33006, Spain

Oviedo 33012, Spain

Sabadell 08208, Spain

Basingstoke RG24 9NA, United Kingdom

Bath BA1 1RL, United Kingdom

Cannock WS11 5XY, United Kingdom

Greenock PA16 0XN, United Kingdom

Leeds LS7 4SA, United Kingdom

London EC1M 6BQ, United Kingdom

Salford M6 8HD, United Kingdom

Stoke-on-trent ST6 7AG, United Kingdom

Wigan WN6 9EW, United Kingdom

Calgary, Alberta T2N 2T9, Canada

Huntington Beach, California 92646, United States

Aventura, Florida 33180, United States

Orlando, Florida 32804, United States

Atlanta, Georgia 30342, United States

Decatur, Georgia 30033, United States

Marietta, Georgia 30060, United States

Idaho Falls, Idaho 83404, United States

Wichita, Kansas 67207, United States

Winnipeg, Manitoba R3A 1M3, Canada

Cumberland, Maryland 21502, United States

St. Claire Shores, Michigan 48081, United States

St John's, Newfoundland and Labrador A1C 5B8, Canada

Charlotte, North Carolina 28210, United States

Greensboro, North Carolina 27408, United States

Kitchener, Ontario N2M 5N6, Canada

Mississauga, Ontario L5M 2V8, Canada

St. Catharines, Ontario L2N 7E4, Canada

Toronto, Ontario M9W 6V1, Canada

Duncansville, Pennsylvania 16635, United States

Montreal, Quebec H1T 2M4, Canada

Quebec City, Quebec G1V 3M7, Canada

Sainte-foy, Quebec G1W 4R4, Canada

Trois-rivieres, Quebec G8Z 1Y2, Canada

Hickory, South Carolina 28602, United States

Houston, Texas 77004, United States

Additional Information

Starting date: September 2010
Last updated: January 10, 2013

Page last updated: August 23, 2015

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