Trial Outcomes & Findings for A Long-Term Extension Study of WA22763 and NA25220 of Subcutaneous RoActemra/Actemra (Tocilizumab) in Patients With Moderate to Severe Rheumatoid Arthritis (NCT NCT01772316)
NCT ID: NCT01772316
Last Updated: 2016-11-07
Results Overview
An AE was defined as any untoward medical occurrence in a clinical investigation participant that was administered study drug, regardless of causal attribution.
COMPLETED
PHASE3
47 participants
Baseline up to follow-up (Week 104)
2016-11-07
Participant Flow
A total of 47 participants were enrolled in the trial and received treatment. All participants enrolled were included in the safety analysis. Of the 47 participants, 13 participants were not included in the statistical analysis for outcome measures because they did not meet eligibility criteria.
Participant milestones
| Measure |
Tocilizumab Subcutaneous (SC)
Participants received Tocilizumab 162 milligram (mg) given as 0.9 milliliter (mL) of a 180 milligram per milliliter (mg/mL) solution administered once a week (for participants entering from NCT01194414) or once every two weeks (for participants entering from NCT01232569) by subcutaneous (SC) injection and as a single fixed dose irrespective of body weight.
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Overall Study
STARTED
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47
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Overall Study
COMPLETED
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40
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Overall Study
NOT COMPLETED
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7
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Reasons for withdrawal
| Measure |
Tocilizumab Subcutaneous (SC)
Participants received Tocilizumab 162 milligram (mg) given as 0.9 milliliter (mL) of a 180 milligram per milliliter (mg/mL) solution administered once a week (for participants entering from NCT01194414) or once every two weeks (for participants entering from NCT01232569) by subcutaneous (SC) injection and as a single fixed dose irrespective of body weight.
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Overall Study
Serious adverse event
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1
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Overall Study
Inform consent withdrawn
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1
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Overall Study
Withdrawn by sponsor decision
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5
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Baseline Characteristics
A Long-Term Extension Study of WA22763 and NA25220 of Subcutaneous RoActemra/Actemra (Tocilizumab) in Patients With Moderate to Severe Rheumatoid Arthritis
Baseline characteristics by cohort
| Measure |
Tocilizumab Subcutaneous (SC)
n=47 Participants
Participants received Tocilizumab 162 mg given as 0.9 mL of a 180 mg/mL solution administered once a week (for participants entering from NCT01194414) or once every two weeks (for participants entering from NCT01232569) by SC injection and as a single fixed dose irrespective of body weight.
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Age, Continuous
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59.3 years
STANDARD_DEVIATION 10.3 • n=5 Participants
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Sex: Female, Male
Female
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40 Participants
n=5 Participants
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Sex: Female, Male
Male
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7 Participants
n=5 Participants
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PRIMARY outcome
Timeframe: Baseline up to follow-up (Week 104)Population: All participants receiving study drug were included in the safety analysis set.
An AE was defined as any untoward medical occurrence in a clinical investigation participant that was administered study drug, regardless of causal attribution.
Outcome measures
| Measure |
Tocilizumab Subcutaneous (SC)
n=47 Participants
Participants received Tocilizumab 162 mg given as 0.9 mL of a 180 mg/mL solution administered once a week (for participants entering from NCT01194414) or once every two weeks (for participants entering from NCT01232569) by SC injection and as a single fixed dose irrespective of body weight.
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Percentage of Participants With an Adverse Event (AE)
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83 percentage of participants
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PRIMARY outcome
Timeframe: Baseline up to follow-up (Week 104)Population: Per-protocol population included all participants who had at least one dose of study medication and at least one safety evaluation after dose administration.
Outcome measures
| Measure |
Tocilizumab Subcutaneous (SC)
n=34 Participants
Participants received Tocilizumab 162 mg given as 0.9 mL of a 180 mg/mL solution administered once a week (for participants entering from NCT01194414) or once every two weeks (for participants entering from NCT01232569) by SC injection and as a single fixed dose irrespective of body weight.
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Percentage of Participants Withdrawn From the Study Due to Lack of Therapeutic Response
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0 percentage of participants
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PRIMARY outcome
Timeframe: Baseline, Week 48Population: Per-protocol population included all participants who had at least one dose of study medication and at least one safety evaluation after dose administration. Number of participants analyzed represent number of participants who were evaluable for the outcome measure.
The DAS28 is a combined index for measuring disease activity in rheumatoid arthritis. The index included swollen joint count (SJC), tender joint count (TJC), acute phase response (ESR or high sensitivity C-reactive protein \[hsCRP\]) and general health status (GH). For this study, ESR was used to calculate DAS28 score. The index was calculated using the following formula: DAS28 = (0.56 × √\[TJC 28\]) + (0.28 × √\[SJC 28\]) + (0.7 × ln\[ESR\]) + (0.014 × GH). The DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity. Change in DAS28ESR=DAS28-ESR at Week 48 - DAS28-ESR at Baseline.
Outcome measures
| Measure |
Tocilizumab Subcutaneous (SC)
n=30 Participants
Participants received Tocilizumab 162 mg given as 0.9 mL of a 180 mg/mL solution administered once a week (for participants entering from NCT01194414) or once every two weeks (for participants entering from NCT01232569) by SC injection and as a single fixed dose irrespective of body weight.
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Change From Baseline in Disease Activity Score 28 - Erythrocyte Sedimentation Rate (DAS28-ESR) at Week 48
Baseline
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2.9 units on a scale
Standard Deviation 1.4
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Change From Baseline in Disease Activity Score 28 - Erythrocyte Sedimentation Rate (DAS28-ESR) at Week 48
Change at Week 48
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-0.832 units on a scale
Standard Deviation 0.292
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PRIMARY outcome
Timeframe: Baseline, Week 96Population: Per-protocol population included all participants who had at least one dose of study medication and at least one safety evaluation after dose administration. Number of participants analyzed represent number of participants who were evaluable for the outcome measure.
The DAS28 is a combined index for measuring disease activity in rheumatoid arthritis. The index included SJC, TJC, acute phase response (ESR or high sensitivity C-reactive protein \[hsCRP\]) and general health status. For this study, ESR was used to calculate DAS28 score. The index was calculated using the following formula: DAS28 = (0.56 × √\[TJC28\]) + (0.28 × √\[SJC28\]) + (0.7 × ln\[ESR\]) + (0.014 × GH). The DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity. Change in DAS28ESR=DAS28-ESR at Week 96 - DAS28-ESR at Baseline.
Outcome measures
| Measure |
Tocilizumab Subcutaneous (SC)
n=30 Participants
Participants received Tocilizumab 162 mg given as 0.9 mL of a 180 mg/mL solution administered once a week (for participants entering from NCT01194414) or once every two weeks (for participants entering from NCT01232569) by SC injection and as a single fixed dose irrespective of body weight.
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Change From Baseline in DAS28-ESR at Week 96
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-0.804 units on a scale
Standard Deviation 0.230
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PRIMARY outcome
Timeframe: Baseline, Week 48Population: Per-protocol population included all participants who had at least one dose of study medication and at least one safety evaluation after dose administration. Number of participants analyzed represent number of participants who were evaluable for the outcome measure.
The SDAI was the numerical sum of five outcome parameter: SJC and TJC, Patient Global Assessment of Disease Activity (PGA) and Investigator Global Assessment of Disease Activity (IGA), and level of hsCRP. The index was calculated using the following formula SDAI = TJC28 + SJC28 + PGA + IGA + CRP. Change in SDAI = SDAI at Week 48 - SDAI at Baseline. SDAI total score = 0-86. SDAI \<=3.3 indicates clinical remission, \>3.4 to 11 = low disease activity, \>11 to 26 = moderate disease activity, and \>26 = high (or severe) disease activity. Here, n signifies the number of subjects evaluable at the specified time points.
Outcome measures
| Measure |
Tocilizumab Subcutaneous (SC)
n=30 Participants
Participants received Tocilizumab 162 mg given as 0.9 mL of a 180 mg/mL solution administered once a week (for participants entering from NCT01194414) or once every two weeks (for participants entering from NCT01232569) by SC injection and as a single fixed dose irrespective of body weight.
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Change From Baseline in Simplified Disease Activity Index (SDAI) at Week 48
Baseline
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12.2 units on a scale
Standard Deviation 10.7
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Change From Baseline in Simplified Disease Activity Index (SDAI) at Week 48
Change at Week 48
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-7.572 units on a scale
Standard Deviation 2.115
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PRIMARY outcome
Timeframe: Baseline, Week 96Population: Per-protocol population included all participants who had at least one dose of study medication and at least one safety evaluation after dose administration. Number of participants analyzed represent number of participants who were evaluable for the outcome measure.
The SDAI was the numerical sum of five outcome parameter: SJC and TJC, PGA and IGA, and level of hsCRP. The index was calculated using the following formula SDAI = TJC28 + SJC28 + PGA + IGA + CRP. Change in SDAI = SDAI at Week 96 - SDAI at Baseline. SDAI total score = 0-86. SDAI \<=3.3 indicates clinical remission, \>3.4 to 11 = low disease activity, \>11 to 26 = moderate disease activity, and \>26 = high (or severe) disease activity.
Outcome measures
| Measure |
Tocilizumab Subcutaneous (SC)
n=30 Participants
Participants received Tocilizumab 162 mg given as 0.9 mL of a 180 mg/mL solution administered once a week (for participants entering from NCT01194414) or once every two weeks (for participants entering from NCT01232569) by SC injection and as a single fixed dose irrespective of body weight.
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Change From Baseline in SDAI at Week 96
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-6.599 units on a scale
Standard Deviation 2.210
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PRIMARY outcome
Timeframe: Baseline, Week 48Population: Per-protocol population included all participants who had at least one dose of study medication and at least one safety evaluation after dose administration. Number of participants analyzed represent number of participants who were evaluable for the outcome measure.
An assessment of 66 joints for swelling and 68 joints for tenderness was made. Joints were assessed and classified as tender/not tender and swollen/not swollen by pressure and joint manipulation on physical examination. A smaller number indicated improvement. Here, 'n' represents the number of participants with a measure at specified time point.
Outcome measures
| Measure |
Tocilizumab Subcutaneous (SC)
n=33 Participants
Participants received Tocilizumab 162 mg given as 0.9 mL of a 180 mg/mL solution administered once a week (for participants entering from NCT01194414) or once every two weeks (for participants entering from NCT01232569) by SC injection and as a single fixed dose irrespective of body weight.
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Change From Baseline in Total Tender Joint Count (TJC) at Week 48
Baseline
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2.5 units on a scale
Standard Deviation 4.1
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Change From Baseline in Total Tender Joint Count (TJC) at Week 48
Change at Week 48
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1.3 units on a scale
Standard Deviation 2.0
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PRIMARY outcome
Timeframe: Baseline, Week 96Population: Per-protocol population included all participants who had at least one dose of study medication and at least one safety evaluation after dose administration. Number of participants analyzed represent number of participants who were evaluable for the outcome measure.
An assessment of 66 joints for swelling and 68 joints for tenderness was made. Joints were assessed and classified as tender/not tender and swollen/not swollen by pressure and joint manipulation on physical examination. A smaller number indicated improvement.
Outcome measures
| Measure |
Tocilizumab Subcutaneous (SC)
n=33 Participants
Participants received Tocilizumab 162 mg given as 0.9 mL of a 180 mg/mL solution administered once a week (for participants entering from NCT01194414) or once every two weeks (for participants entering from NCT01232569) by SC injection and as a single fixed dose irrespective of body weight.
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Change From Baseline in Total TJC at Week 96
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1.5 units on a scale
Standard Deviation 3.6
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PRIMARY outcome
Timeframe: Baseline, Week 48Population: Per-protocol population included all participants who had at least one dose of study medication and at least one safety evaluation after dose administration.
An assessment of 66 joints for swelling and 68 joints for tenderness was made. Joints were assessed and classified as tender/not tender and swollen/not swollen by pressure and joint manipulation on physical examination. A negative number indicated improvement.
Outcome measures
| Measure |
Tocilizumab Subcutaneous (SC)
n=34 Participants
Participants received Tocilizumab 162 mg given as 0.9 mL of a 180 mg/mL solution administered once a week (for participants entering from NCT01194414) or once every two weeks (for participants entering from NCT01232569) by SC injection and as a single fixed dose irrespective of body weight.
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|---|---|
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Change From Baseline in Swollen Joint Count (SJC) at Week 48
Baseline
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1.8 units on a scale
Standard Deviation 3.4
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Change From Baseline in Swollen Joint Count (SJC) at Week 48
Change at Week 48
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-1.531 units on a scale
Standard Deviation 0.587
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PRIMARY outcome
Timeframe: Baseline, Week 96Population: Per-protocol population included all participants who had at least one dose of study medication and at least one safety evaluation after dose administration.
An assessment of 66 joints for swelling and 68 joints for tenderness was made. Joints were assessed and classified as tender/not tender and swollen/not swollen by pressure and joint manipulation on physical examination. Change in SJC = SJC at Week 96 - SJC at Baseline. A negative number indicated improvement.
Outcome measures
| Measure |
Tocilizumab Subcutaneous (SC)
n=34 Participants
Participants received Tocilizumab 162 mg given as 0.9 mL of a 180 mg/mL solution administered once a week (for participants entering from NCT01194414) or once every two weeks (for participants entering from NCT01232569) by SC injection and as a single fixed dose irrespective of body weight.
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Change From Baseline in SJC at Week 96
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-1.188 units on a scale
Standard Deviation 0.543
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SECONDARY outcome
Timeframe: Week 48, Week 96Population: Per-protocol population included all participants who had at least one dose of study medication and at least one safety evaluation after dose administration.
Outcome measures
| Measure |
Tocilizumab Subcutaneous (SC)
n=34 Participants
Participants received Tocilizumab 162 mg given as 0.9 mL of a 180 mg/mL solution administered once a week (for participants entering from NCT01194414) or once every two weeks (for participants entering from NCT01232569) by SC injection and as a single fixed dose irrespective of body weight.
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Percentage of Participants With Remission (DAS28 <2.6 or SDAI </=3.3) at Weeks 48 and 96
DAS <2.6 at Week 48
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71.9 percentage of participants
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Percentage of Participants With Remission (DAS28 <2.6 or SDAI </=3.3) at Weeks 48 and 96
DAS <2.6 at Week 96
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62.5 percentage of participants
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Percentage of Participants With Remission (DAS28 <2.6 or SDAI </=3.3) at Weeks 48 and 96
SDAI </=3.3 at Week 48
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28.6 percentage of participants
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Percentage of Participants With Remission (DAS28 <2.6 or SDAI </=3.3) at Weeks 48 and 96
SDAI </=3.3 at Week 96
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29.6 percentage of participants
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SECONDARY outcome
Timeframe: Randomization of first participant to clinical cutoff date (19MAY2015) (approximately 29 months)Population: Per-protocol population included all participants who had at least one dose of study medication and at least one safety evaluation after dose administration.
Outcome measures
| Measure |
Tocilizumab Subcutaneous (SC)
n=34 Participants
Participants received Tocilizumab 162 mg given as 0.9 mL of a 180 mg/mL solution administered once a week (for participants entering from NCT01194414) or once every two weeks (for participants entering from NCT01232569) by SC injection and as a single fixed dose irrespective of body weight.
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Percentage of Participants With Disease-Modifying Antirheumatic Drugs (DMARDs)/Corticosteroid Dose Reductions and/or Discontinuation
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38.2 percentage of participants
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SECONDARY outcome
Timeframe: Baseline, Week 48, Week 96Population: Per-protocol population included all participants who had at least one dose of study medication and at least one safety evaluation after dose administration. Here, 'n' represents the number of participants with a measure at the specified time point.
This assessment represents the patient's overall assessment of their current disease activity on a 100 millimeter (mm) horizontal VAS. The extreme left end of the line should be described as "no disease activity" (symptom free and no arthritis symptoms) and the extreme right end as "maximum disease activity" (maximum arthritis disease activity). Scores ranged from 0 to 100 with a higher score indicating more disease activity. A negative change score indicated less disease activity.
Outcome measures
| Measure |
Tocilizumab Subcutaneous (SC)
n=34 Participants
Participants received Tocilizumab 162 mg given as 0.9 mL of a 180 mg/mL solution administered once a week (for participants entering from NCT01194414) or once every two weeks (for participants entering from NCT01232569) by SC injection and as a single fixed dose irrespective of body weight.
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Patient Global Visual Analog Score (VAS) at Specified Time Points
Baseline (n=34)
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30.8 units on a scale
Standard Deviation 21.8
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Patient Global Visual Analog Score (VAS) at Specified Time Points
Week 48 (n=33)
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30.0 units on a scale
Standard Deviation 22.6
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Patient Global Visual Analog Score (VAS) at Specified Time Points
Week 96 (n=33)
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26.0 units on a scale
Standard Deviation 21.8
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SECONDARY outcome
Timeframe: Baseline, Week 48, Week 96Population: Per-protocol population included all participants who had at least one dose of study medication and at least one safety evaluation after dose administration. Here, 'n' represents the number of participants with a measure at the specified time point.
This assessment represents the patient's assessment of his/her current level of pain on a 100 mm horizontal VAS. The extreme left end of the line should be described as "no pain" and the extreme right end as "unbearable pain". Scores ranged from 0 to 100 with a higher score indicating more pain. A negative change score indicated less pain.
Outcome measures
| Measure |
Tocilizumab Subcutaneous (SC)
n=34 Participants
Participants received Tocilizumab 162 mg given as 0.9 mL of a 180 mg/mL solution administered once a week (for participants entering from NCT01194414) or once every two weeks (for participants entering from NCT01232569) by SC injection and as a single fixed dose irrespective of body weight.
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Patient Pain VAS Score at Specified Time Points
Week 96 (n=33)
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27.0 units on a scale
Standard Deviation 22.2
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Patient Pain VAS Score at Specified Time Points
Baseline (n=34)
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32.4 units on a scale
Standard Deviation 21.8
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Patient Pain VAS Score at Specified Time Points
Week 48 (n=33)
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29.8 units on a scale
Standard Deviation 21.3
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SECONDARY outcome
Timeframe: Baseline, Week 48, Week 96Population: Per-protocol population included all participants who had at least one dose of study medication and at least one safety evaluation after dose administration. Here, 'n' represents the number of participants with a measure at the specified time point.
The HAQ-DI is a questionnaire specific for rheumatoid arthritis and consists of 20 questions referring to 8 domains: Dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities. Minimum score was 0, maximum score was 3. A smaller score indicated improvement.
Outcome measures
| Measure |
Tocilizumab Subcutaneous (SC)
n=34 Participants
Participants received Tocilizumab 162 mg given as 0.9 mL of a 180 mg/mL solution administered once a week (for participants entering from NCT01194414) or once every two weeks (for participants entering from NCT01232569) by SC injection and as a single fixed dose irrespective of body weight.
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Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Specified Time Points
Baseline (n=34)
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0.8 units on a scale
Standard Deviation 0.6
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Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Specified Time Points
Week 48 (n=33)
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0.7 units on a scale
Standard Deviation 0.5
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Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Specified Time Points
Week 96 (n=33)
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0.8 units on a scale
Standard Deviation 0.7
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Adverse Events
Tocilizumab Subcutaneous (SC)
Serious adverse events
| Measure |
Tocilizumab Subcutaneous (SC)
n=47 participants at risk
Participants received Tocilizumab 162 mg given as 0.9 mL of a 180 mg/mL solution administered once a week (for participants entering from NCT01194414) or once every two weeks (for participants entering from NCT01232569) by SC injection and as a single fixed dose irrespective of body weight.
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Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer
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2.1%
1/47 • Baseline up to follow-up (Week 104)
An AE was defined as any untoward medical occurrence in a clinical investigation participant that was administered study drug, regardless of causal attribution.
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Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon cancer
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2.1%
1/47 • Baseline up to follow-up (Week 104)
An AE was defined as any untoward medical occurrence in a clinical investigation participant that was administered study drug, regardless of causal attribution.
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Renal and urinary disorders
Renal colic
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2.1%
1/47 • Baseline up to follow-up (Week 104)
An AE was defined as any untoward medical occurrence in a clinical investigation participant that was administered study drug, regardless of causal attribution.
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Other adverse events
| Measure |
Tocilizumab Subcutaneous (SC)
n=47 participants at risk
Participants received Tocilizumab 162 mg given as 0.9 mL of a 180 mg/mL solution administered once a week (for participants entering from NCT01194414) or once every two weeks (for participants entering from NCT01232569) by SC injection and as a single fixed dose irrespective of body weight.
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|---|---|
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Blood and lymphatic system disorders
Neutropenia
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6.4%
3/47 • Baseline up to follow-up (Week 104)
An AE was defined as any untoward medical occurrence in a clinical investigation participant that was administered study drug, regardless of causal attribution.
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Infections and infestations
Gastroenteritis
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6.4%
3/47 • Baseline up to follow-up (Week 104)
An AE was defined as any untoward medical occurrence in a clinical investigation participant that was administered study drug, regardless of causal attribution.
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Infections and infestations
Respiratory tract infection
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27.7%
13/47 • Baseline up to follow-up (Week 104)
An AE was defined as any untoward medical occurrence in a clinical investigation participant that was administered study drug, regardless of causal attribution.
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Infections and infestations
Urinary tract infection
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10.6%
5/47 • Baseline up to follow-up (Week 104)
An AE was defined as any untoward medical occurrence in a clinical investigation participant that was administered study drug, regardless of causal attribution.
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Injury, poisoning and procedural complications
Wound
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6.4%
3/47 • Baseline up to follow-up (Week 104)
An AE was defined as any untoward medical occurrence in a clinical investigation participant that was administered study drug, regardless of causal attribution.
|
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Musculoskeletal and connective tissue disorders
Back pain
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14.9%
7/47 • Baseline up to follow-up (Week 104)
An AE was defined as any untoward medical occurrence in a clinical investigation participant that was administered study drug, regardless of causal attribution.
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Musculoskeletal and connective tissue disorders
Pain in extremity
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6.4%
3/47 • Baseline up to follow-up (Week 104)
An AE was defined as any untoward medical occurrence in a clinical investigation participant that was administered study drug, regardless of causal attribution.
|
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Respiratory, thoracic and mediastinal disorders
Cough
|
6.4%
3/47 • Baseline up to follow-up (Week 104)
An AE was defined as any untoward medical occurrence in a clinical investigation participant that was administered study drug, regardless of causal attribution.
|
Additional Information
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