Clinical trial NCT01209689: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Spondylitis, Ankylosing
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2010-09-27
Enrollment: 113
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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).
* 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* Traditional disease-modifying anti-rheumatic drugs (DMARDs) must be withdrawn for at least 4 weeks prior to baseline (methotrexate, sulfasalazine, and hydroxychloroquine or chloroquine may be allowed if at stable dose for at least 4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.

Primary outcomes:
measure: Percentage of ASsessment in Ankylosing Spondylitis 20 (ASAS20) Responders at Week 12
timeFrame: Baseline to Week 12
Secondary outcomes:
Other outcomes:
Locations:
city: Huntington Beach
country: United States
state: California
city: Aventura
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: Orlando
country: United States
state: Florida
city: Tampa
country: United States
state: Florida
city: Atlanta
country: United States
state: Georgia
city: Decatur
country: United States
state: Georgia
city: Marietta
country: United States
state: Georgia
city: Idaho Falls
country: United States
state: Idaho
city: Wichita
country: United States
state: Kansas
city: Hagerstown
country: United States
state: Maryland
city: St. Claire Shores
country: United States
state: Michigan
city: Freehold
country: United States
state: New Jersey
city: Asheville
country: United States
state: North Carolina
city: Charlotte
country: United States
state: North Carolina
city: Greensboro
country: United States
state: North Carolina
city: Duncansville
country: United States
state: Pennsylvania
city: Austin
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: Heidelberg
country: Australia
city: Hobart
country: Australia
city: Sydney
country: Australia
city: Woodville
country: Australia
city: Bruxelles
country: Belgium
city: Gent
country: Belgium
city: Kortrijk
country: Belgium
city: Liege
country: Belgium
city: Yvoir
country: Belgium
city: Cuiabá
country: Brazil
city: Goiania
country: Brazil
city: Sao Paulo
country: Brazil
city: Sao Paulo
country: Brazil
city: São Paulo
country: Brazil
city: Plovdiv
country: Bulgaria
city: Plovdiv
country: Bulgaria
city: Sofia
country: Bulgaria
city: Sofia
country: Bulgaria
city: Sofia
country: Bulgaria
city: Calgary
country: Canada
state: Alberta
city: Hamilton
country: Canada
state: Ontario
city: Kitchener
country: Canada
state: Ontario
city: Mississauga
country: Canada
state: Ontario
city: St. Catharines
country: Canada
state: Ontario
city: Toronto
country: Canada
state: Ontario
city: Toronto
country: Canada
state: Ontario
city: Montreal
country: Canada
state: Quebec
city: Quebec City
country: Canada
state: Quebec
city: Trois-rivières
country: Canada
state: Quebec
city: St. John's
country: Canada
city: Bruntal
country: Czech Republic
city: Hlucin
country: Czech Republic
city: Olomouc
country: Czech Republic
city: Prague
country: Czech Republic
city: Uherske Hradiste
country: Czech Republic
city: Zlin
country: Czech Republic
city: Esbjerg
country: Denmark
city: Hellerup
country: Denmark
city: Vejle
country: Denmark
city: Besancon
country: France
city: Bordeaux
country: France
city: Boulogne-billancourt
country: France
city: Creteil
country: France
city: Grenoble
country: France
city: Le Kremlin Bicetre
country: France
city: Lyon Cedex 3
country: France
city: Montpellier
country: France
city: Orléans Cedex 2
country: France
city: Paris
country: France
city: Paris
country: France
city: Rouen Cedex
country: France
city: Strasbourg
country: France
city: Vandoeuvre-les-nancy
country: France
city: Berlin
country: Germany
city: Berlin
country: Germany
city: Erlangen
country: Germany
city: Frankfurt
country: Germany
city: Gommern
country: Germany
city: Hamburg
country: Germany
city: Hannover
country: Germany
city: Heidelberg
country: Germany
city: Herne
country: Germany
city: Köln
country: Germany
city: München
country: Germany
city: Regensburg
country: Germany
city: Rostock
country: Germany
city: Tuebingen
country: Germany
city: Würzburg
country: Germany
city: Bangalore
country: India
city: Bangalore
country: India
city: Jaipur
country: India
city: New Delhi
country: India
city: Secunderabad
country: India
city: Ferrara
country: Italy
city: Firenze
country: Italy
city: Monserrato
country: Italy
city: Padova
country: Italy
city: Pisa
country: Italy
city: Prato
country: Italy
city: Reggio Emilia
country: Italy
city: Roma
country: Italy
city: Siena
country: Italy
city: Kaunas
country: Lithuania
city: Klaipeda
country: Lithuania
city: Amsterdam
country: Netherlands
city: Amsterdam
country: Netherlands
city: Amsterdam
country: Netherlands
city: Bydgoszcz
country: Poland
city: Krakow
country: Poland
city: Lublin
country: Poland
city: Poznan
country: Poland
city: Torun
country: Poland
city: Warszawa
country: Poland
city: Wroclaw
country: Poland
city: Kosice
country: Slovakia
city: Piestany
country: Slovakia
city: Cape Town
country: South Africa
city: Cape Town
country: South Africa
city: Durban
country: South Africa
city: Pinelands
country: South Africa
city: Pretoria
country: South Africa
city: Stellenbosch
country: South Africa
city: Alcorcon
country: Spain
city: Barcelona
country: Spain
city: Córdoba
country: Spain
city: La Coruna
country: Spain
city: Lugo
country: Spain
city: Madrid
country: Spain
city: Madrid
country: Spain
city: Madrid
country: Spain
city: Oviedo
country: Spain
city: Oviedo
country: Spain
city: Sabadell
country: Spain
city: Basingstoke
country: United Kingdom
city: Bath
country: United Kingdom
city: Greenock
country: United Kingdom
city: Leeds
country: United Kingdom
city: London
country: United Kingdom
city: Salford
country: United Kingdom
city: Stoke-on-trent
country: United Kingdom
city: Wigan
country: United Kingdom
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.