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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01209702




Registration number
NCT01209702
Ethics application status
Date submitted
24/09/2010
Date registered
27/09/2010
Date last updated
11/02/2013

Titles & IDs
Public title
A Study of RoActemra/Actemra (Tocilizumab) in Patients With Ankylosing Spondylitis Who Have Failed Treatment With NSAIDs
Scientific 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 naïve to TNF Antagonist Therapy NSAIDs
Secondary ID [1] 0 0
2009-017443-34
Secondary ID [2] 0 0
NA22823
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Spondylitis, Ankylosing 0 0
Condition category
Condition code
Inflammatory and Immune System 0 0 0 0
Other inflammatory or immune system disorders
Musculoskeletal 0 0 0 0
Other muscular and skeletal disorders
Inflammatory and Immune System 0 0 0 0
Rheumatoid arthritis

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - tocilizumab
Treatment: Drugs - Placebo

Placebo comparator: 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.

Experimental: 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.

Placebo comparator: 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.

Experimental: 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.

Experimental: 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.


Treatment: Other: tocilizumab
Administered intravenously (iv) every 4 weeks

Treatment: Drugs: Placebo
Placebo to tocilizumab administered intravenously every 4 weeks

Intervention code [1] 0 0
Treatment: Other
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Part 1: Percentage of Participants Achieving a 20% Improvement in Assessment in Ankylosing Spondylitis (ASAS20) at Week 12
Timepoint [1] 0 0
Baseline and Week 12
Primary outcome [2] 0 0
Part 2: Percentage of Participants Achieving a 20% Improvement in Assessment in Ankylosing Spondylitis (ASAS20) at Week 12
Timepoint [2] 0 0
Baseline and Week 12
Secondary outcome [1] 0 0
Part 2: Percentage of Participants Achieving a 20% Improvement in Assessment in Ankylosing Spondylitis (ASAS20) at Week 24
Timepoint [1] 0 0
Baseline and Week 24
Secondary outcome [2] 0 0
Percentage of Participants Who Achieved a Value <2 in Each of the 4 ASAS Parameters at Week 12
Timepoint [2] 0 0
Week 12
Secondary outcome [3] 0 0
Percentage of Participants Achieving a 40% Improvement in Assessment in Ankylosing Spondylitis (ASAS40) at Week 12
Timepoint [3] 0 0
Baseline and Week 12
Secondary outcome [4] 0 0
Part 2: Percentage of Participants Achieving a 40% Improvement in Assessment in Ankylosing Spondylitis (ASAS40) at Week 24
Timepoint [4] 0 0
Baseline and Week 24
Secondary outcome [5] 0 0
Change From Baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)
Timepoint [5] 0 0
Baseline and Week 12
Secondary outcome [6] 0 0
Change From Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI)
Timepoint [6] 0 0
Baseline and Week 12
Secondary outcome [7] 0 0
Change From Baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI)
Timepoint [7] 0 0
Baseline and Week 12
Secondary outcome [8] 0 0
Change From Baseline in C-Reactive Protein
Timepoint [8] 0 0
Baseline and Week 12
Secondary outcome [9] 0 0
Part 2: Area Under the Plasma Concentration Versus Time Curve of Tocilizumab
Timepoint [9] 0 0
Week 12, pre-dose and at the end of infusion, on the 2nd and 7th day of Week 12, 14 days post-dose (Week 14) and 28 days post-dose (pre-dose of Week 16 infusion).
Secondary outcome [10] 0 0
Part 2: Peak Plasma Concentration of Tocilizumab
Timepoint [10] 0 0
Week 12, pre-dose and at the end of infusion, on the 2nd and 7th day of Week 12, 14 days post-dose (Week 14) and 28 days post-dose (pre-dose of Week 16 infusion).
Secondary outcome [11] 0 0
Part 2: Elimination Half-life of Tocilizumab
Timepoint [11] 0 0
Week 12, pre-dose and at the end of infusion, on the 2nd and 7th day of Week 12, 14 days post-dose (Week 14) and 28 days post-dose (pre-dose of Week 16 infusion).
Secondary outcome [12] 0 0
Part 2: Clearance of Tocilizumab
Timepoint [12] 0 0
Week 12, pre-dose and at the end of infusion, on the 2nd and 7th day of Week 12, 14 days post-dose (Week 14) and 28 days post-dose (pre-dose of Week 16 infusion).
Secondary outcome [13] 0 0
Part 2: Volume of Distribution of Tocilizumab
Timepoint [13] 0 0
Week 12, pre-dose and at the end of infusion, on the 2nd and 7th day of Week 12, 14 days post-dose (Week 14) and 28 days post-dose (pre-dose of Week 16 infusion).
Secondary outcome [14] 0 0
Change From Baseline in the Level of Interleukin-6
Timepoint [14] 0 0
Baseline and Week 12
Secondary outcome [15] 0 0
Change From Baseline in Level of Soluble Interleukin-6 Receptor
Timepoint [15] 0 0
Baseline and Week 12
Secondary outcome [16] 0 0
Number of Participants With Anti-tocilizumab Antibodies
Timepoint [16] 0 0
From Baseline until end of study (a maximum treatment duration of 40 weeks).
Secondary outcome [17] 0 0
Part 2: Radiographic Change According to the Modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS)
Timepoint [17] 0 0
Baseline and Week 104
Secondary outcome [18] 0 0
Part 2: Percentage of Participants With a Reduction of Magnetic Resonance Imaging (MRI) Proven Spinal Inflammation
Timepoint [18] 0 0
Baseline and Week 24
Secondary outcome [19] 0 0
Part 1: The Number of Participants With Adverse Events
Timepoint [19] 0 0
Up to 40 weeks

Eligibility
Key inclusion 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
- Adelaide
Recruitment hospital [2] 0 0
- Heidelberg
Recruitment hospital [3] 0 0
- Hobart
Recruitment hospital [4] 0 0
- Malvern East
Recruitment hospital [5] 0 0
- Maroochydore
Recruitment hospital [6] 0 0
- Sydney
Recruitment hospital [7] 0 0
- Woodville
Recruitment postcode(s) [1] 0 0
5041 - Adelaide
Recruitment postcode(s) [2] 0 0
3084 - Heidelberg
Recruitment postcode(s) [3] 0 0
7000 - Hobart
Recruitment postcode(s) [4] 0 0
3145 - Malvern East
Recruitment postcode(s) [5] 0 0
4558 - Maroochydore
Recruitment postcode(s) [6] 0 0
2050 - Sydney
Recruitment postcode(s) [7] 0 0
5011 - Woodville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Georgia
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United States of America
State/province [4] 0 0
Idaho
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United States of America
State/province [5] 0 0
Kansas
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United States of America
State/province [6] 0 0
Maryland
Country [7] 0 0
United States of America
State/province [7] 0 0
Michigan
Country [8] 0 0
United States of America
State/province [8] 0 0
North Carolina
Country [9] 0 0
United States of America
State/province [9] 0 0
Pennsylvania
Country [10] 0 0
United States of America
State/province [10] 0 0
South Carolina
Country [11] 0 0
United States of America
State/province [11] 0 0
Texas
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Belgium
State/province [12] 0 0
Bruxelles
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Belgium
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Kortrijk
Country [14] 0 0
Belgium
State/province [14] 0 0
Liege
Country [15] 0 0
Belgium
State/province [15] 0 0
Yvoir
Country [16] 0 0
Brazil
State/province [16] 0 0
Cuiabá
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Brazil
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Goiania
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Brazil
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Sao Paulo
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Brazil
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São Paulo
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Bulgaria
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Plovdiv
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Bulgaria
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Ruse
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Bulgaria
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Sevlievo
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Sofia
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Alberta
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Manitoba
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Newfoundland and Labrador
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Ontario
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Bruntal
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Hlucin
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Praha 4
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Sokolov
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Uherske Hradiste
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Zlin
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Besancon
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Kazan
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Moscow
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Voronezh
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Kosice
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Piestany
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Cape Town
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Durban
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Pretoria
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South Africa
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Stellenbosch
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Barcelona
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Córdoba
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La Coruna
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Lugo
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Oviedo
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Sabadell
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United Kingdom
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Basingstoke
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Bath
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Cannock
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Greenock
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Leeds
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Salford
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Stoke-on-trent
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United Kingdom
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Wigan

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Hoffmann-La Roche
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.