Trial Outcomes & Findings for 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 (NCT NCT01209689)
NCT ID: NCT01209689
Last Updated: 2013-01-17
Results Overview
ASAS20 was defined as an improvement of ≥ 20% and an absolute improvement of ≥ 10 units on a 0-100 visual analog scale (VAS) from Baseline to Week 12 in 3 of 4 domains: 1-Patient global assessment (with extremes labelled none and severe), 2-Pain assessment (average total and nocturnal pain scores with extremes labelled no pain and most severe pain), 3-Function (represented by the Bath Ankylosing Spondylitis (BAS) Functional Index \[BASFI\] average of 10 questions regarding ability to perform specific tasks with extremes labelled easy and impossible), and 4-Inflammation (average of the last 2 questions on the 6-question BAS Disease Activity Index \[BASDAI\] concerning morning stiffness intensity with extremes labelled none and very severe and duration between 0 and 2 or more hours); and the absence of deterioration (of at least 20% and absolute change of at least 10 units on a 0-100 mm scale) in the remaining domain.
TERMINATED
PHASE3
113 participants
Baseline to Week 12
2013-01-17
Participant Flow
Because of the early termination of the study and the limited and varying duration of treatment, the 4 mg/kg and 8 mg/kg tocilizumab dose groups were combined in the efficacy and safety analyses and reporting.
Participant milestones
| Measure |
Tocilizumab 4 or 8 mg/kg
Patients received tocilizumab 4 or 8 mg/kg intravenously every 4 weeks for 24 weeks.
|
Placebo
Patients received placebo to tocilizumab intravenously every 4 weeks for 24 weeks.
|
|---|---|---|
|
Overall Study
STARTED
|
91
|
22
|
|
Overall Study
COMPLETED
|
0
|
0
|
|
Overall Study
NOT COMPLETED
|
91
|
22
|
Reasons for withdrawal
| Measure |
Tocilizumab 4 or 8 mg/kg
Patients received tocilizumab 4 or 8 mg/kg intravenously every 4 weeks for 24 weeks.
|
Placebo
Patients received placebo to tocilizumab intravenously every 4 weeks for 24 weeks.
|
|---|---|---|
|
Overall Study
Insufficient Therapeutic Response
|
7
|
2
|
|
Overall Study
Refused Treatment
|
8
|
3
|
|
Overall Study
Adverse Event
|
4
|
0
|
|
Overall Study
Violation of Selection Criteria at Entry
|
1
|
0
|
|
Overall Study
Failure to Return
|
3
|
0
|
|
Overall Study
Sponsor's Decision to Stop the Study
|
68
|
17
|
Baseline Characteristics
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
Baseline characteristics by cohort
| Measure |
Tocilizumab 4 or 8 mg/kg
n=91 Participants
Patients received tocilizumab 4 or 8 mg/kg intravenously every 4 weeks for 24 weeks.
|
Placebo
n=22 Participants
Patients received placebo to tocilizumab intravenously every 4 weeks for 24 weeks.
|
Total
n=113 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age Continuous
|
44.1 years
STANDARD_DEVIATION 12.08 • n=5 Participants
|
45.0 years
STANDARD_DEVIATION 12.66 • n=7 Participants
|
44.3 years
STANDARD_DEVIATION 12.14 • n=5 Participants
|
|
Sex: Female, Male
Female
|
29 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
37 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
62 Participants
n=5 Participants
|
14 Participants
n=7 Participants
|
76 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline to Week 12Population: Intent-to-treat population: All randomized patients who received at least 1 dose of treatment. The analysis only included assessments while patients were receiving double-blind treatment and that occurred prior to withdrawal or the date when all patients were unblinded (15 Jul 2011). Patients who withdrew or escaped were considered non-responders.
ASAS20 was defined as an improvement of ≥ 20% and an absolute improvement of ≥ 10 units on a 0-100 visual analog scale (VAS) from Baseline to Week 12 in 3 of 4 domains: 1-Patient global assessment (with extremes labelled none and severe), 2-Pain assessment (average total and nocturnal pain scores with extremes labelled no pain and most severe pain), 3-Function (represented by the Bath Ankylosing Spondylitis (BAS) Functional Index \[BASFI\] average of 10 questions regarding ability to perform specific tasks with extremes labelled easy and impossible), and 4-Inflammation (average of the last 2 questions on the 6-question BAS Disease Activity Index \[BASDAI\] concerning morning stiffness intensity with extremes labelled none and very severe and duration between 0 and 2 or more hours); and the absence of deterioration (of at least 20% and absolute change of at least 10 units on a 0-100 mm scale) in the remaining domain.
Outcome measures
| Measure |
Tocilizumab 4 or 8 mg/kg
n=79 Participants
Patients received tocilizumab 4 or 8 mg/kg intravenously every 4 weeks for 24 weeks.
|
Placebo
n=21 Participants
Patients received placebo to tocilizumab intravenously every 4 weeks for 24 weeks.
|
|---|---|---|
|
Percentage of ASsessment in Ankylosing Spondylitis 20 (ASAS20) Responders at Week 12
|
12.7 Percentage of patients
|
14.3 Percentage of patients
|
Adverse Events
Tocilizumab
Placebo
Serious adverse events
| Measure |
Tocilizumab
n=95 participants at risk
Patients randomized to tocilizumab who received intravenous infusions of 4 mg/kg or 8 mg/kg tocilizumab once every 4 weeks for 24 weeks and patients randomized to placebo who switched or escaped to tocilizumab treatment.
|
Placebo
n=22 participants at risk
Patients received placebo to tocilizumab intravenously every 4 weeks for 24 weeks.
|
|---|---|---|
|
Immune system disorders
Anaphylactic reaction
|
2.1%
2/95 • For the tocilizumab group, adverse events (AE) were reported from randomization to the end of the study. For the placebo group, AEs were reported from randomization only until participants escaped or switched to tocilizumab.
Safety population: Patients who received at least 1 dose of study medication and had at least 1 post-baseline safety assessment. Patients were assigned to groups as treated; 95 patients in the combined tocilizumab groups, including 4 patients randomized to placebo who received escape therapy of 8 mg/kg tocilizumab at Week 16.
|
0.00%
0/22 • For the tocilizumab group, adverse events (AE) were reported from randomization to the end of the study. For the placebo group, AEs were reported from randomization only until participants escaped or switched to tocilizumab.
Safety population: Patients who received at least 1 dose of study medication and had at least 1 post-baseline safety assessment. Patients were assigned to groups as treated; 95 patients in the combined tocilizumab groups, including 4 patients randomized to placebo who received escape therapy of 8 mg/kg tocilizumab at Week 16.
|
|
Musculoskeletal and connective tissue disorders
Ankylosing spondylitis
|
1.1%
1/95 • For the tocilizumab group, adverse events (AE) were reported from randomization to the end of the study. For the placebo group, AEs were reported from randomization only until participants escaped or switched to tocilizumab.
Safety population: Patients who received at least 1 dose of study medication and had at least 1 post-baseline safety assessment. Patients were assigned to groups as treated; 95 patients in the combined tocilizumab groups, including 4 patients randomized to placebo who received escape therapy of 8 mg/kg tocilizumab at Week 16.
|
0.00%
0/22 • For the tocilizumab group, adverse events (AE) were reported from randomization to the end of the study. For the placebo group, AEs were reported from randomization only until participants escaped or switched to tocilizumab.
Safety population: Patients who received at least 1 dose of study medication and had at least 1 post-baseline safety assessment. Patients were assigned to groups as treated; 95 patients in the combined tocilizumab groups, including 4 patients randomized to placebo who received escape therapy of 8 mg/kg tocilizumab at Week 16.
|
|
Musculoskeletal and connective tissue disorders
Sacroiliitis
|
1.1%
1/95 • For the tocilizumab group, adverse events (AE) were reported from randomization to the end of the study. For the placebo group, AEs were reported from randomization only until participants escaped or switched to tocilizumab.
Safety population: Patients who received at least 1 dose of study medication and had at least 1 post-baseline safety assessment. Patients were assigned to groups as treated; 95 patients in the combined tocilizumab groups, including 4 patients randomized to placebo who received escape therapy of 8 mg/kg tocilizumab at Week 16.
|
0.00%
0/22 • For the tocilizumab group, adverse events (AE) were reported from randomization to the end of the study. For the placebo group, AEs were reported from randomization only until participants escaped or switched to tocilizumab.
Safety population: Patients who received at least 1 dose of study medication and had at least 1 post-baseline safety assessment. Patients were assigned to groups as treated; 95 patients in the combined tocilizumab groups, including 4 patients randomized to placebo who received escape therapy of 8 mg/kg tocilizumab at Week 16.
|
|
Infections and infestations
Pasteurella infection
|
1.1%
1/95 • For the tocilizumab group, adverse events (AE) were reported from randomization to the end of the study. For the placebo group, AEs were reported from randomization only until participants escaped or switched to tocilizumab.
Safety population: Patients who received at least 1 dose of study medication and had at least 1 post-baseline safety assessment. Patients were assigned to groups as treated; 95 patients in the combined tocilizumab groups, including 4 patients randomized to placebo who received escape therapy of 8 mg/kg tocilizumab at Week 16.
|
0.00%
0/22 • For the tocilizumab group, adverse events (AE) were reported from randomization to the end of the study. For the placebo group, AEs were reported from randomization only until participants escaped or switched to tocilizumab.
Safety population: Patients who received at least 1 dose of study medication and had at least 1 post-baseline safety assessment. Patients were assigned to groups as treated; 95 patients in the combined tocilizumab groups, including 4 patients randomized to placebo who received escape therapy of 8 mg/kg tocilizumab at Week 16.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Thyroid cancer
|
1.1%
1/95 • For the tocilizumab group, adverse events (AE) were reported from randomization to the end of the study. For the placebo group, AEs were reported from randomization only until participants escaped or switched to tocilizumab.
Safety population: Patients who received at least 1 dose of study medication and had at least 1 post-baseline safety assessment. Patients were assigned to groups as treated; 95 patients in the combined tocilizumab groups, including 4 patients randomized to placebo who received escape therapy of 8 mg/kg tocilizumab at Week 16.
|
0.00%
0/22 • For the tocilizumab group, adverse events (AE) were reported from randomization to the end of the study. For the placebo group, AEs were reported from randomization only until participants escaped or switched to tocilizumab.
Safety population: Patients who received at least 1 dose of study medication and had at least 1 post-baseline safety assessment. Patients were assigned to groups as treated; 95 patients in the combined tocilizumab groups, including 4 patients randomized to placebo who received escape therapy of 8 mg/kg tocilizumab at Week 16.
|
Other adverse events
| Measure |
Tocilizumab
n=95 participants at risk
Patients randomized to tocilizumab who received intravenous infusions of 4 mg/kg or 8 mg/kg tocilizumab once every 4 weeks for 24 weeks and patients randomized to placebo who switched or escaped to tocilizumab treatment.
|
Placebo
n=22 participants at risk
Patients received placebo to tocilizumab intravenously every 4 weeks for 24 weeks.
|
|---|---|---|
|
Nervous system disorders
Headache
|
6.3%
6/95 • For the tocilizumab group, adverse events (AE) were reported from randomization to the end of the study. For the placebo group, AEs were reported from randomization only until participants escaped or switched to tocilizumab.
Safety population: Patients who received at least 1 dose of study medication and had at least 1 post-baseline safety assessment. Patients were assigned to groups as treated; 95 patients in the combined tocilizumab groups, including 4 patients randomized to placebo who received escape therapy of 8 mg/kg tocilizumab at Week 16.
|
4.5%
1/22 • For the tocilizumab group, adverse events (AE) were reported from randomization to the end of the study. For the placebo group, AEs were reported from randomization only until participants escaped or switched to tocilizumab.
Safety population: Patients who received at least 1 dose of study medication and had at least 1 post-baseline safety assessment. Patients were assigned to groups as treated; 95 patients in the combined tocilizumab groups, including 4 patients randomized to placebo who received escape therapy of 8 mg/kg tocilizumab at Week 16.
|
Additional Information
Medical Communications
Hoffmann-La Roche
Results disclosure agreements
- Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
- Publication restrictions are in place
Restriction type: OTHER