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

NCT01209702 | Terminated Phase 3 Results

• 2 other identifiers: NA228232009-017443-34
• Study Type: interventional
• Target: 306
• Locations: 18 countries
• Sites: 139

Brief Summary

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 naïve 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.

Conditions

Spondylitis, Ankylosing

Outcome Measures

Primary Outcomes (2)

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

  ASAS is composed of four domains. To achieve an ASAS20 response required improvement of ≥20% and ≥ 1 unit (10 mm) in at least 3 domains and no worsening of ≥ 20 % and ≥ 1 unit (10 mm) in the remaining domain. * The patient's global assessment of current disease status, measured on a 100 mm visual analog scale (VAS), from symptom-free / no AS symptoms (0) to maximum AS disease severity (100). * The patient's overall assessment of the severity of spinal pain based on responses to 2 questions assessed on a 100 mm VAS, from no pain (0) to most severe pain (100). The spinal pain score is the mean of these 2 questions. * The function component was measured by the Bath Ankylosing Spondylitis Functional Index (BASFI). The patient provides self-assessment of 10 questions on a 100 mm VAS. The BASFI score is the mean of these values. * The inflammation component of the ASAS was determined by the mean of questions 5 and 6 of the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI).

  Baseline and Week 12

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

  ASAS is composed of four domains. To achieve an ASAS20 response required improvement of ≥20% and ≥ 1 unit (10 mm) in at least 3 domains and no worsening of ≥ 20 % and ≥ 1 unit (10 mm) in the remaining domain. * The patient's global assessment of current disease status, measured on a 100 mm visual analog scale (VAS), from symptom-free / no AS symptoms (0) to maximum AS disease severity (100). * The patient's overall assessment of the severity of spinal pain based on responses to 2 questions assessed on a 100 mm VAS, from no pain (0) to most severe pain (100). The spinal pain score is the mean of these 2 questions. * The function component was measured by the Bath Ankylosing Spondylitis Functional Index (BASFI). The patient provides self-assessment of 10 questions on a 100 mm VAS. The BASFI score is the mean of these values. * The inflammation component of the ASAS was determined by the mean of questions 5 and 6 of the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI).

  Baseline and Week 12

Secondary Outcomes (19)

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

  Baseline and Week 24

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

  Week 12

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

  Baseline and Week 12

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

  Baseline and Week 24

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

  Baseline and Week 12

Study Arms (5)

Part 1: Placebo

PLACEBO COMPARATOR

Participants received intravenous infusions of placebo once every 4 weeks until Week 12. Following the Week 12 visit, participants who completed Part 1 of the study received open-label 8 mg/kg tocilizumab through Week 208.

Drug: Placebo

Part 1: Tocilizumab

EXPERIMENTAL

Participants received intravenous infusions of 8 mg/kg tocilizumab once every 4 weeks until Week 12. Following the Week 12 visit, participants who completed Part 1 of the study received open-label 8 mg/kg tocilizumab through Week 208.

Biological: tocilizumab

Part 2: Placebo

PLACEBO COMPARATOR

Participants received intravenous infusions of placebo once every 4 weeks until Week 24. Participants who did not attain an ASsessment in Ankylosing Spondylitis-20 (ASAS20) response at Week 16 were, at the investigator's discretion, eligible to receive open-label escape therapy consisting of 8 mg/kg tocilizumab. After Week 24, participants were to receive open-label treatment with 8 mg/kg tocilizumab every 4 weeks until Week 104. At the completion of Week 104, all Part 2 participants were to receive tocilizumab 8 mg/kg in the common open-label extension phase, however the study was terminated prior to any participants reaching this stage.

Drug: Placebo

Part 2: Tocilizumab 4 mg/kg

EXPERIMENTAL

Participants received intravenous infusions of 4 mg/kg tocilizumab once every 4 weeks until Week 24. Participants who did not attain an ASAS20 response at Week 16 were, at the investigator's discretion, eligible to receive open-label escape therapy consisting of 8 mg/kg tocilizumab. After Week 24, participants were to receive open-label treatment with 8 mg/kg tocilizumab every 4 weeks until Week 104. At the completion of Week 104, all Part 2 participants were to receive tocilizumab 8 mg/kg in the common open-label extension phase, however the study was terminated prior to any participants reaching this stage.

Biological: tocilizumab

Part 2: Tocilizumab 8 mg/kg

EXPERIMENTAL

Participants received intravenous infusions of 8 mg/kg tocilizumab once every 4 weeks until Week 24. Participants who did not attain an ASAS20 response at Week 16 were, at the investigator's discretion, eligible to receive open-label escape therapy consisting of 8 mg/kg tocilizumab. After Week 24, participants were to receive open-label treatment with 8 mg/kg tocilizumab every 4 weeks until Week 104. At the completion of Week 104, all Part 2 participants were to receive tocilizumab 8 mg/kg in the common open-label extension phase, however the study was terminated prior to any participants reaching this stage.

Biological: tocilizumab

Interventions

tocilizumab BIOLOGICAL

Administered intravenously (iv) every 4 weeks

Also known as: RoActemra/Actemra

Part 1: Tocilizumab; Part 2: Tocilizumab 4 mg/kg; Part 2: Tocilizumab 8 mg/kg

Placebo DRUG

Placebo to tocilizumab administered intravenously every 4 weeks

Part 1: Placebo; Part 2: 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)
• 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

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
• Treatment with tumor necrosis factor (TNF) antagonist therapy at any time prior to baseline
• 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 (139)

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Huntington Beach, California, 92646, United States

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Aventura, Florida, 33180, United States

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Orlando, Florida, 32804, 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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Cumberland, Maryland, 21502, United States

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Saint Claire Shores, Michigan, 48081, 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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Hickory Grove, South Carolina, 28602, United States

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Houston, Texas, 77004, United States

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Adelaide, 5041, Australia

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Heidelberg, 3084, Australia

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Hobart, 7000, Australia

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Malvern East, 3145, Australia

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Maroochydore, 4558, 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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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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Rousse, 7002, Bulgaria

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Sevlievo, 5400, 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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Sofia, 1709, Bulgaria

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Calgary, Alberta, T2N 2T9, Canada

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Winnipeg, Manitoba, R3A 1M3, Canada

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St. John's, Newfoundland and Labrador, A1C 5B8, 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, 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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Sainte-Foy, Quebec, G1W 4R4, Canada

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Trois-Rivières, Quebec, G8Z 1Y2, 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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Prague, 140 00, Czechia

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Prague, 148 00, Czechia

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Praha 4 Nusle, 140 00, Czechia

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Sokolov, 356 01, Czechia

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Uherské Hradiště, 686 01, Czechia

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Zlín, 760 01, Czechia

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Besançon, 25030, 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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Montpellier, 34295, France

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Paris, 75679, France

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Strasbourg, 67098, France

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Toulouse, 31059, 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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Gommern, 39245, Germany

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Hanover, 30625, Germany

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Würzburg, 97080, Germany

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Ahmedabad, 380009, India

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Bangalore, 560003, India

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Bangalore, 560034, India

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Bangalore, 560054, India

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Bangalore, 560076, India

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Hyderabad, 500 033, India

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Jaipur, 302 015, India

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New Delhi, 110029, India

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New Delhi, 110076, 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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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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Vilnius, LT-08661, Lithuania

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Bydgoszcz, 85-168, Poland

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Krakow, 30-119, Poland

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Krakow, 31-121, Poland

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Lublin, 20-607, 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, 00-235, Poland

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Warsaw, 00-909, Poland

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Warsaw, 02-256, Poland

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Wroclaw, 51-124, Poland

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Kazan', 4420029, Russia

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Moscow, 115522, Russia

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Moscow, 123060, Russia

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Voronezh, 394066, Russia

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Yaroslavl, 150062, Russia

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Košice, 040 66, Slovakia

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Piešťany, 921 01, Slovakia

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Cape Town, 7405, South Africa

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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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Pretoria, 0002, South Africa

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Pretoria, 0084, South Africa

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Pretoria, 0184, South Africa

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Stellenbosch, 7600, South Africa

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A Coruña, 15006, 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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Cannock, WS11 5XY, 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: Hoffman-LaRoche

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: September 1, 2010
• Primary Completion: May 1, 2011
• Study Completion: December 1, 2011
• Last Updated: February 11, 2013
• Results First Posted: February 11, 2013

Record last verified: 2013-01

Locations

ZA (8); IN (10); ES (10); US (15); SL (2); CZ (10); RU (5); AU (7); CA (11); LI (3); DE (6); BE (4); BU (8); FR (8); IT (7); GB (9); PL (11); BR (5)