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

NCT ID: NCT01209702

Last Updated: 2013-02-11

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 306 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-09-30
• Study Completion Date: 2011-12-31

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.

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.

Conditions

Spondylitis, Ankylosing

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Part 1: Placebo

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo to tocilizumab administered intravenously every 4 weeks

Part 1: Tocilizumab

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.

Group Type: EXPERIMENTAL

tocilizumab

Intervention Type: BIOLOGICAL

Administered intravenously (iv) every 4 weeks

Part 2: Placebo

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo to tocilizumab administered intravenously every 4 weeks

Part 2: Tocilizumab 4 mg/kg

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.

Group Type: EXPERIMENTAL

tocilizumab

Intervention Type: BIOLOGICAL

Administered intravenously (iv) every 4 weeks

Part 2: Tocilizumab 8 mg/kg

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.

Group Type: EXPERIMENTAL

tocilizumab

Intervention Type: BIOLOGICAL

Administered intravenously (iv) every 4 weeks

Interventions

tocilizumab

Administered intravenously (iv) every 4 weeks

Intervention Type: BIOLOGICAL

Placebo

Placebo to tocilizumab administered intravenously every 4 weeks

Intervention Type: DRUG

Other Intervention Names

RoActemra/Actemra

Eligibility 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)
• 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 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hoffmann-La Roche

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

Huntington Beach, California, United States

Aventura, Florida, United States

Orlando, Florida, United States

Atlanta, Georgia, United States

Decatur, Georgia, United States

Marietta, Georgia, United States

Idaho Falls, Idaho, United States

Wichita, Kansas, United States

Cumberland, Maryland, United States

Saint Claire Shores, Michigan, United States

Charlotte, North Carolina, United States

Greensboro, North Carolina, United States

Duncansville, Pennsylvania, United States

Hickory Grove, South Carolina, United States

Houston, Texas, United States

Adelaide, , Australia

Heidelberg, , Australia

Hobart, , Australia

Malvern East, , Australia

Maroochydore, , Australia

Sydney, , Australia

Woodville, , Australia

Brussels, , Belgium

Kortrijk, , Belgium

Liège, , Belgium

Yvoir, , Belgium

Cuiabá, , Brazil

Goiânia, , Brazil

São Paulo, , Brazil

São Paulo, , Brazil

São Paulo, , Brazil

Plovdiv, , Bulgaria

Plovdiv, , Bulgaria

Rousse, , Bulgaria

Sevlievo, , Bulgaria

Sofia, , Bulgaria

Sofia, , Bulgaria

Sofia, , Bulgaria

Sofia, , Bulgaria

Calgary, Alberta, Canada

Winnipeg, Manitoba, Canada

St. John's, Newfoundland and Labrador, Canada

Kitchener, Ontario, Canada

Mississauga, Ontario, Canada

St. Catharines, Ontario, Canada

Toronto, Ontario, Canada

Montreal, Quebec, Canada

Québec, Quebec, Canada

Sainte-Foy, Quebec, Canada

Trois-Rivières, Quebec, Canada

Bruntál, , Czechia

Hlučín, , Czechia

Olomouc, , Czechia

Prague, , Czechia

Prague, , Czechia

Prague, , Czechia

Praha 4 Nusle, , Czechia

Sokolov, , Czechia

Uherské Hradiště, , Czechia

Zlín, , Czechia

Besançon, , France

Boulogne-Billancourt, , France

Créteil, , France

Grenoble, , France

Montpellier, , France

Paris, , France

Strasbourg, , France

Toulouse, , France

Berlin, , Germany

Berlin, , Germany

Cologne, , Germany

Gommern, , Germany

Hanover, , Germany

Würzburg, , Germany

Ahmedabad, , India

Bangalore, , India

Bangalore, , India

Bangalore, , India

Bangalore, , India

Hyderabad, , India

Jaipur, , India

New Delhi, , India

New Delhi, , India

Secunderabad, , India

Ferrara, , Italy

Florence, , Italy

Monserrato, , Italy

Prato, , Italy

Reggio Emilia, , Italy

Roma, , Italy

Siena, , Italy

Kaunas, , Lithuania

Klaipėda, , Lithuania

Vilnius, , Lithuania

Bydgoszcz, , Poland

Krakow, , Poland

Krakow, , Poland

Lublin, , Poland

Lublin, , Poland

Poznan, , Poland

Torun, , Poland

Warsaw, , Poland

Warsaw, , Poland

Warsaw, , Poland

Wroclaw, , Poland

Kazan', , Russia

Moscow, , Russia

Moscow, , Russia

Voronezh, , Russia

Yaroslavl, , Russia

Košice, , Slovakia

Piešťany, , Slovakia

Cape Town, , South Africa

Cape Town, , South Africa

Cape Town, , South Africa

Durban, , South Africa

Pretoria, , South Africa

Pretoria, , South Africa

Pretoria, , South Africa

Stellenbosch, , South Africa

A Coruña, , Spain

Barcelona, , Spain

Córdoba, , Spain

Lugo, , Spain

Madrid, , Spain

Madrid, , Spain

Madrid, , Spain

Oviedo, , Spain

Oviedo, , Spain

Sabadell, , Spain

Basingstoke, , United Kingdom

Bath, , United Kingdom

Cannock, , United Kingdom

Greenock, , United Kingdom

Leeds, , United Kingdom

London, , United Kingdom

Salford, , United Kingdom

Stoke-on-Trent, , United Kingdom

Wigan, , United Kingdom

Countries

United States; Australia; Belgium; Brazil; Bulgaria; Canada; Czechia; France; Germany; India; Italy; Lithuania; Poland; Russia; Slovakia; South Africa; Spain; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 23765873 (View on PubMed)

Other Identifiers

2009-017443-34

Identifier Type: -

Identifier Source: secondary_id

NA22823

Identifier Type: -

Identifier Source: org_study_id