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

January 10, 2013 updated by: Hoffmann-La Roche

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

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.

Study Overview

Status

Terminated

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.

Study Type

Interventional

Enrollment (Actual)

306

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Adelaide, Australia, 5041
      • Heidelberg, Australia, 3084
      • Hobart, Australia, 7000
      • Malvern East, Australia, 3145
      • Maroochydore, Australia, 4558
      • Sydney, Australia, 2050
      • Woodville, Australia, 5011
      • Bruxelles, Belgium, 1200
      • Kortrijk, Belgium, 8500
      • Liege, Belgium, 4000
      • Yvoir, Belgium, 5530
      • Cuiabá, Brazil, 78025-000
      • Goiania, Brazil, 74110-120
      • Sao Paulo, Brazil, 04039-000
      • Sao Paulo, Brazil, 04026-000
      • São Paulo, Brazil, 04266-010
      • Plovdiv, Bulgaria, 4002
      • Plovdiv, Bulgaria, 4003
      • Ruse, Bulgaria, 7002
      • Sevlievo, Bulgaria, 5400
      • Sofia, Bulgaria, 1233
      • Sofia, Bulgaria, 1709
      • Sofia, Bulgaria, 1606
      • Sofia, Bulgaria, 1612
    • Alberta
      • Calgary, Alberta, Canada, T2N 2T9
    • Manitoba
      • Winnipeg, Manitoba, Canada, R3A 1M3
    • Newfoundland and Labrador
      • St John's, Newfoundland and Labrador, Canada, A1C 5B8
    • Ontario
      • Kitchener, Ontario, Canada, N2M 5N6
      • Mississauga, Ontario, Canada, L5M 2V8
      • St. Catharines, Ontario, Canada, L2N 7E4
      • Toronto, Ontario, Canada, M9W 6V1
    • Quebec
      • Montreal, Quebec, Canada, H1T 2M4
      • Quebec City, Quebec, Canada, G1V 3M7
      • Sainte-foy, Quebec, Canada, G1W 4R4
      • Trois-rivieres, Quebec, Canada, G8Z 1Y2
      • Bruntal, Czech Republic, 792 01
      • Hlucin, Czech Republic, 748 01
      • Olomouc, Czech Republic, 775 20
      • Prague, Czech Republic, 12850
      • Praha 11, Czech Republic, 148 00
      • Praha 4, Czech Republic, 140 00
      • Praha 4 Nusle, Czech Republic, 140 00
      • Sokolov, Czech Republic, 356 01
      • Uherske Hradiste, Czech Republic, 686 01
      • Zlin, Czech Republic, 760 01
      • Besancon, France, 25030
      • Boulogne-billancourt, France, 92104
      • Creteil, France, 94010
      • Grenoble, France, 38042
      • Montpellier, France, 34295
      • Paris, France, 75679
      • Strasbourg, France, 67098
      • Toulouse, France, 31059
      • Berlin, Germany, 10117
      • Berlin, Germany, 14059
      • Gommern, Germany, 39245
      • Hannover, Germany, 30625
      • Köln, Germany, 50924
      • Würzburg, Germany, 97080
      • Ahmedabad, India, 380009
      • Bangalore, India, 560034
      • Bangalore, India, 560054
      • Bangalore, India, 560076
      • Bangalore, India, 560003
      • Hyderabad, India, 500 033
      • Jaipur, India, 302 015
      • New Delhi, India, 110029
      • New Delhi, India, 110076
      • Secunderabad, India, 500003
      • Ferrara, Italy, 44100
      • Firenze, Italy, 50141
      • Monserrato, Italy, 09042
      • Prato, Italy, 59100
      • Reggio Emilia, Italy, 42100
      • Roma, Italy, 00161
      • Siena, Italy, 53100
      • Kaunas, Lithuania, 50009
      • Klaipeda, Lithuania, 92288
      • Vilnius, Lithuania, LT-08661
      • Bydgoszcz, Poland, 85-168
      • Krakow, Poland, 30-119
      • Krakow, Poland, 31-121
      • Lublin, Poland, 20-954
      • Lublin, Poland, 20-607
      • Poznan, Poland, 60-218
      • Torun, Poland, 87-100
      • Warszawa, Poland, 02-256
      • Warszawa, Poland, 00-909
      • Warszawa, Poland, 00-235
      • Wroclaw, Poland, 51-124
      • Kazan, Russian Federation, 4420029
      • Moscow, Russian Federation, 115522
      • Moscow, Russian Federation, 123060
      • Voronezh, Russian Federation, 394066
      • Yaroslavl, Russian Federation, 150062
      • Kosice, Slovakia, 040 66
      • Piestany, Slovakia, 921 01
      • Cape Town, South Africa, 7500
      • Cape Town, South Africa, 8001
      • Cape Town, South Africa, 7405
      • Durban, South Africa, 4001
      • Pretoria, South Africa, 0002
      • Pretoria, South Africa, 0084
      • Pretoria, South Africa, 0184
      • Stellenbosch, South Africa, 7600
      • Barcelona, Spain, 08036
      • Córdoba, Spain, 14004
      • La Coruna, Spain, 15006
      • Lugo, Spain, 27004
      • Madrid, Spain, 28046
      • Madrid, Spain, 28222
      • Madrid, Spain, 28009
      • Oviedo, Spain, 33006
      • Oviedo, Spain, 33012
      • Sabadell, Spain, 08208
      • Basingstoke, United Kingdom, RG24 9NA
      • Bath, United Kingdom, BA1 1RL
      • Cannock, United Kingdom, WS11 5XY
      • Greenock, United Kingdom, PA16 0XN
      • Leeds, United Kingdom, LS7 4SA
      • London, United Kingdom, EC1M 6BQ
      • Salford, United Kingdom, M6 8HD
      • Stoke-on-trent, United Kingdom, ST6 7AG
      • Wigan, United Kingdom, WN6 9EW
    • California
      • Huntington Beach, California, United States, 92646
    • Florida
      • Aventura, Florida, United States, 33180
      • Orlando, Florida, United States, 32804
    • Georgia
      • Atlanta, Georgia, United States, 30342
      • Decatur, Georgia, United States, 30033
      • Marietta, Georgia, United States, 30060
    • Idaho
      • Idaho Falls, Idaho, United States, 83404
    • Kansas
      • Wichita, Kansas, United States, 67207
    • Maryland
      • Cumberland, Maryland, United States, 21502
    • Michigan
      • St. Claire Shores, Michigan, United States, 48081
    • North Carolina
      • Charlotte, North Carolina, United States, 28210
      • Greensboro, North Carolina, United States, 27408
    • Pennsylvania
      • Duncansville, Pennsylvania, United States, 16635
    • South Carolina
      • Hickory, South Carolina, United States, 28602
    • Texas
      • Houston, Texas, United States, 77004

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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.
Placebo to tocilizumab administered intravenously every 4 weeks
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.
Administered intravenously (iv) every 4 weeks
Other Names:
  • RoActemra/Actemra
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.
Placebo to tocilizumab administered intravenously every 4 weeks
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.
Administered intravenously (iv) every 4 weeks
Other Names:
  • RoActemra/Actemra
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.
Administered intravenously (iv) every 4 weeks
Other Names:
  • RoActemra/Actemra

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Part 1: Percentage of Participants Achieving a 20% Improvement in Assessment in Ankylosing Spondylitis (ASAS20) at Week 12
Time Frame: Baseline and 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
Time Frame: Baseline and 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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Part 2: Percentage of Participants Achieving a 20% Improvement in Assessment in Ankylosing Spondylitis (ASAS20) at Week 24
Time Frame: Baseline and Week 24

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 24
Percentage of Participants Who Achieved a Value <2 in Each of the 4 ASAS Parameters at Week 12
Time Frame: Week 12

Assessment in Ankylosing Spondylitis (ASAS) is composed of four domains.

  • 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 mean of 10 self-assessment questions on a 100 mm VAS.
  • 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).

Each of the above 4 domains are measured on a scale from 0-100 mm, but reported on a 0-10 cm scale. A score of less than 2 units (20 mm) in each domain is defined as partial remission.

Week 12
Percentage of Participants Achieving a 40% Improvement in Assessment in Ankylosing Spondylitis (ASAS40) at Week 12
Time Frame: Baseline and Week 12

ASAS is composed of four domains. To achieve an ASAS40 response required improvement of ≥40% and ≥ 2 units (20 mm) in at least 3 domains and no worsening at all 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 40% Improvement in Assessment in Ankylosing Spondylitis (ASAS40) at Week 24
Time Frame: Baseline and Week 24

ASAS is composed of four domains. To achieve an ASAS40 response required improvement of ≥40% and ≥ 2 units (20 mm) in at least 3 domains and no worsening at all 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 24
Change From Baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)
Time Frame: Baseline and Week 12

The BASDAI is a patient-administered assessment of 6 parameters specific to AS. The following parameters were assessed on a 100-mm horizontal visual analogue: fatigue, spinal pain, peripheral arthritis, enthesitis, intensity of morning stiffness, and duration of morning stiffness. For questions 1 to 5, the left-hand extreme of the line (0) represents "none" (symptom-free) and the right-hand extreme (100) represents "very severe" (maximum severity). For question 6, a time axis was used, with the left-hand extreme of the line representing "0 hours" and the right-hand extreme representing "2 or more hours". The BASDAI score was calculated as follows:

BASDAI = [Q1 + Q2 + Q3 + Q4 + (Q5 + Q6)/2]/5. The total score is tabulated on a scale from 0 (best) to 10 cm (worst).

Baseline and Week 12
Change From Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI)
Time Frame: Baseline and Week 12
The Bath Ankylosing Spondylitis Functional Index (BASFI) is an assessment of function in AS patients. The participant provides their assessment of their ability to perform 10 activities on a 100 mm horizontal visual analog scale (VAS) ranging from 0 (easy) to 100 (impossible). The BASFI score is the mean of these values and is tabulated on a 0 (best) to 10 (worst) cm scale.
Baseline and Week 12
Change From Baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI)
Time Frame: Baseline and Week 12

The Bath Ankylosing Spondylitis Metrology Index linear function is a combined index of 5 clinical measurements (performed by the Joint Assessor) which reflect axial mobility in the AS patient. The measurements to assess mobility are:

  1. Tragus-to-wall;
  2. Modified Schober (lumbar flexion);
  3. Cervical rotation;
  4. Lateral spinal flexion;
  5. Intermalleolar distance.

The BASMI linear result is the average of the 5 assessments and ranges from 0 to 10. The higher the BASMI score the more severe the patient's limitation of movement due to their AS.

Baseline and Week 12
Change From Baseline in C-Reactive Protein
Time Frame: Baseline and Week 12
Levels of C-reactive protein (CRP) were measured from blood samples taken at Baseline and at Week 12.
Baseline and Week 12
Part 2: Area Under the Plasma Concentration Versus Time Curve of Tocilizumab
Time Frame: 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).
Area under the plasma concentration versus time curve (AUC) of tocilizumab at steady state after 12 weeks of treatment.
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).
Part 2: Peak Plasma Concentration of Tocilizumab
Time Frame: 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).
The peak plasma concentration (Cmax) of tocilizumab at steady state after 12 weeks of treatment.
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).
Part 2: Elimination Half-life of Tocilizumab
Time Frame: 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).
Elimination half-life of tocilizumab at steady state after 12 weeks of treatment.
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).
Part 2: Clearance of Tocilizumab
Time Frame: 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).
Clearance of tocilizumab at steady state after 12 weeks of treatment.
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).
Part 2: Volume of Distribution of Tocilizumab
Time Frame: 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).
Volume of distribution of tocilizumab at steady state after 12 weeks of treatment.
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).
Change From Baseline in the Level of Interleukin-6
Time Frame: Baseline and Week 12

Interleukin-6 levels were measured from blood samples taken pre-dose at Baseline and after 12 weeks of treatment.

The analysis was not performed for participants in Part 2 due to premature study termination.

Baseline and Week 12
Change From Baseline in Level of Soluble Interleukin-6 Receptor
Time Frame: Baseline and Week 12

Soluble Interleukin-6 receptor levels were measured from blood samples taken pre-dose at Baseline and after 12 weeks of treatment.

The analysis was not performed for participants in Part 2 due to premature study termination.

Baseline and Week 12
Number of Participants With Anti-tocilizumab Antibodies
Time Frame: From Baseline until end of study (a maximum treatment duration of 40 weeks).
A positive anti-tocilizumab antibody result was defined as a negative assay result at Baseline and a positive post-baseline screening assay with positive confirmation or neutralizing assay at the same visit.
From Baseline until end of study (a maximum treatment duration of 40 weeks).
Part 2: Radiographic Change According to the Modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS)
Time Frame: Baseline and Week 104

Radiographs were to be assessed using the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS). The mSASSS is a four-point scoring system for lateral radiographs of the lumbar and cervical spine and has been shown to reliably track disease progression over time, where:

  • 0 = No abnormality;
  • 1 = Erosion, sclerosis, or squaring;
  • 2 = Syndesmophyte;
  • 3 = Total bony bridging at each site.
Baseline and Week 104
Part 2: Percentage of Participants With a Reduction of Magnetic Resonance Imaging (MRI) Proven Spinal Inflammation
Time Frame: Baseline and Week 24
Magentic resonance imaging of the axial skeleton was to be performed at Baseline and Week 24. MRI scans will be evaluated using the ankylosing spondylitis spinal MRI activity (ASspiMRI-a) score, grading activity (0-6) per vertebral unit in 23 units.
Baseline and Week 24
Part 1: The Number of Participants With Adverse Events
Time Frame: Up to 40 weeks
A serious adverse event (AE) is any event that is fatal, life-threatening, requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant or requires intervention to prevent one or other of the outcomes listed above. The intensity of each AE was graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 4.02. A severe AE was any event of Grade 4 (life-threatening consequences; urgent intervention indicated) or 5 (death related to AE).
Up to 40 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Publications and helpful links

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Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2010

Primary Completion (Actual)

May 1, 2011

Study Completion (Actual)

December 1, 2011

Study Registration Dates

First Submitted

September 24, 2010

First Submitted That Met QC Criteria

September 24, 2010

First Posted (Estimate)

September 27, 2010

Study Record Updates

Last Update Posted (Estimate)

February 11, 2013

Last Update Submitted That Met QC Criteria

January 10, 2013

Last Verified

January 1, 2013

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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