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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/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
Other interventions - 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.


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

Treatment: Drugs: Placebo
Placebo to tocilizumab administered intravenously every 4 weeks
Intervention code [1] 0 0
Other interventions
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
Terminated
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/09/2010
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/12/2011
Sample size
Target
Accrual to date
Final
306
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
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Florida
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Idaho
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Kansas
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Maryland
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Michigan
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North Carolina
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South Carolina
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Texas
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Belgium
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Bruxelles
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Belgium
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Kortrijk
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Liege
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Yvoir
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Cuiabá
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Durban
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Pretoria
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Stellenbosch
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Spain
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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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Madrid
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Oviedo
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Spain
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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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London
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Salford
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Stoke-on-trent
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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
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT01209702
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



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT01209702