Clinical Trial Results:
Prospective, multicentre, placebo controlled, double-blind study to compare the efficacy of maintenance treatment with Tocilizumab with or without glucocorticoid discontinuation in rheumatoid arthritis patients
Summary
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EudraCT number |
2014-004673-16 |
Trial protocol |
DE FR IT |
Global end of trial date |
09 Feb 2018
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Results information
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Results version number |
v1(current) |
This version publication date |
23 Feb 2019
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First version publication date |
23 Feb 2019
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Other versions |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
MA29585
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
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Sponsors
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Sponsor organisation name |
Hoffmann- LaRoche
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Sponsor organisation address |
Grenzacherstrasse 124, Basel, Switzerland, CH-4070
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Public contact |
Roche Trial Information Hotline, F. Hoffmann-La Roche AG., +41 61 6878333, global.trial_information@roche.com
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Scientific contact |
Roche Trial Information Hotline, F. Hoffmann-La Roche AG., +41 61 6878333, global.trial_information@roche.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
23 Apr 2018
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
09 Feb 2018
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Global end of trial reached? |
Yes
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Global end of trial date |
09 Feb 2018
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To compare the change in disease activity as assessed by Disease Activity Score 28 Erythrocyte Sedimentation Rate (DAS28 ESR) from randomization to Week 24 post-randomization, in subjects with stable low disease activity (LDA, DAS28 ESR score ≤ 3.2) who have been randomized to either continue or taper prednisone in a double-blinded fashion.
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Protection of trial subjects |
The study was conducted in accordance with the principles of the "Declaration of Helsinki" and Good Clinical Practice (GCP) according to the regulations and procedures described in the protocol. All the investigators were trained according to the applicable Sponsor standard operating procedures, and strictly adhered to the stated provisions. This was documented by investigator's signature on the protocol agreeing to carry out all of its terms in accordance with the applicable regulations and to follow International Conference on Harmonization (ICH) GCP guidelines. Approval from Institutional Review Boards (IRBs) and Ethics Committee (EC) was obtained before study start and was documented in a letter to investigator specifying the date the committee met, and granted approval. Approval from relevant competent authority was also obtained prior to starting the study. Protocol amendments were prepared by the Sponsor, and were submitted to IRB/EC and to Regulatory Authorities in accordance with the local regulatory requirements. Audits were performed by the Sponsor Quality Assurance group in compliance with GCP. An independent Data Monitoring Committee (iDMC) shared responsibility for evaluating the safety of the subjects participating in the trial at regular intervals throughout the study.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
29 Mar 2016
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
France: 13
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Country: Number of subjects enrolled |
Germany: 129
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Country: Number of subjects enrolled |
Italy: 15
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Country: Number of subjects enrolled |
Russian Federation: 52
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Country: Number of subjects enrolled |
Serbia: 44
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Country: Number of subjects enrolled |
Tunisia: 6
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Worldwide total number of subjects |
259
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EEA total number of subjects |
157
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
198
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From 65 to 84 years |
60
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85 years and over |
1
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Recruitment
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Recruitment details |
- | ||||||||||||||||||||||||||||||
Pre-assignment
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Screening details |
Overall, 314 patients were enrolled into the study. 246 subjects were Track TCZ-naive subjects and 68 subjects were Track TCZ-experienced subjects. A total of 9 TCZ-naive subjects failed to complete 4 weeks’ treatment with SPOL prednisone 5 mg/day and were withdrawn from the study prior to randomization. | ||||||||||||||||||||||||||||||
Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | ||||||||||||||||||||||||||||||
Roles blinded |
Subject, Investigator, Monitor | ||||||||||||||||||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Tocilizumab+prednisone (tapering dose) | ||||||||||||||||||||||||||||||
Arm description |
Participants will receive tocilizumab at a dose of 162 milligram (mg) once a week subcutaneously or 8 mg/kg intravenously every 4 weeks; and prednisone at a dose of 5 milligram per day (mg/day) with 1 mg decrements every 4 weeks or matching placebo orally for 24 weeks. | ||||||||||||||||||||||||||||||
Arm type |
Active comparator | ||||||||||||||||||||||||||||||
Investigational medicinal product name |
Tocilizumab
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Injection, Infusion
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Routes of administration |
Subcutaneous use, Intravenous use
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Dosage and administration details |
Participants will receive tocilizumab at a dose of 162 milligram (mg) once a week subcutaneously or 8 mg/kg intravenously every 4 weeks
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Investigational medicinal product name |
Prednisone
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Prednisone at a dose of 5 milligram per day (mg/day) with 1 mg decrements every 4 weeks or matching placebo orally for 24 weeks.
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Investigational medicinal product name |
Prednisone
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Prednisone at a dose of 5 milligram per day (mg/day) or matching placebo orally for 24 weeks.
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Investigational medicinal product name |
Placebo matched to prednisone
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Prednisone at a dose of 5 milligram per day (mg/day) with 1 mg decrements every 4 weeks or matching placebo orally for 24 weeks.
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Arm title
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Tocilizumab+prednisone (constant dose) | ||||||||||||||||||||||||||||||
Arm description |
Participants will receive tocilizumab at a dose of 162 milligram (mg) once a week subcutaneously or 8 mg/kg intravenously every 4 weeks; and prednisone at a dose of 5 milligram per day (mg/day) or matching placebo orally for 24 weeks. | ||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||
Investigational medicinal product name |
Tocilizumab
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Injection, Infusion
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Routes of administration |
Subcutaneous use, Intravenous use
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Dosage and administration details |
Participants will receive tocilizumab at a dose of 162 milligram (mg) once a week subcutaneously or 8 mg/kg intravenously every 4 weeks
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Investigational medicinal product name |
Placebo matched to prednisone
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Prednisone at a dose of 5 milligram per day (mg/day) with 1 mg decrements every 4 weeks or matching placebo orally for 24 weeks.
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Baseline characteristics reporting groups
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Reporting group title |
Tocilizumab+prednisone (tapering dose)
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Reporting group description |
Participants will receive tocilizumab at a dose of 162 milligram (mg) once a week subcutaneously or 8 mg/kg intravenously every 4 weeks; and prednisone at a dose of 5 milligram per day (mg/day) with 1 mg decrements every 4 weeks or matching placebo orally for 24 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Tocilizumab+prednisone (constant dose)
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Reporting group description |
Participants will receive tocilizumab at a dose of 162 milligram (mg) once a week subcutaneously or 8 mg/kg intravenously every 4 weeks; and prednisone at a dose of 5 milligram per day (mg/day) or matching placebo orally for 24 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Tocilizumab+prednisone (tapering dose)
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Reporting group description |
Participants will receive tocilizumab at a dose of 162 milligram (mg) once a week subcutaneously or 8 mg/kg intravenously every 4 weeks; and prednisone at a dose of 5 milligram per day (mg/day) with 1 mg decrements every 4 weeks or matching placebo orally for 24 weeks. | ||
Reporting group title |
Tocilizumab+prednisone (constant dose)
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Reporting group description |
Participants will receive tocilizumab at a dose of 162 milligram (mg) once a week subcutaneously or 8 mg/kg intravenously every 4 weeks; and prednisone at a dose of 5 milligram per day (mg/day) or matching placebo orally for 24 weeks. |
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End point title |
Change from baseline in Disease Activity Score in 28 joints - Erythrocyte Sedimentation Rate (DAS28-ESR) at Week 24 post-randomization | ||||||||||||
End point description |
Comparing the impact on disease activity of continued versus tapered prednisone in Rheumatoid Arthritis participants with stable low disease activity (LDA) (DAS28-ESR score ≤ 3.2). The DAS28 is a combined index for measuring disease activity in RA. The index includes swollen and tender joint counts, ESR, and general health status.
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End point type |
Primary
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End point timeframe |
Baseline to Week 24
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Statistical analysis title |
ANCOVA | ||||||||||||
Comparison groups |
Tocilizumab+prednisone (constant dose) v Tocilizumab+prednisone (tapering dose)
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Number of subjects included in analysis |
259
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
= 0.001 | ||||||||||||
Method |
ANCOVA | ||||||||||||
Parameter type |
Least Square Means | ||||||||||||
Point estimate |
0.613
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
0.346 | ||||||||||||
upper limit |
0.879 |
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End point title |
Treatment Success | ||||||||||||
End point description |
Comparing the proportion of participants who continued versus tapered prednisone with LDA (DAS28-ESR score ≤ 3.2) at Week 24 who did not suffer a flare due to RA and who showed no confirmed adrenal insufficiency requiring replacement therapy.
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End point type |
Secondary
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End point timeframe |
Week 24
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Statistical analysis title |
Odds Ratio | ||||||||||||
Comparison groups |
Tocilizumab+prednisone (constant dose) v Tocilizumab+prednisone (tapering dose)
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Number of subjects included in analysis |
259
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Analysis specification |
Pre-specified
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Analysis type |
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P-value |
= 0.018 | ||||||||||||
Method |
Regression, Logistic | ||||||||||||
Parameter type |
Odds ratio (OR) | ||||||||||||
Point estimate |
0.5
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
0.285 | ||||||||||||
upper limit |
0.889 | ||||||||||||
Statistical analysis title |
Relative Risk | ||||||||||||
Comparison groups |
Tocilizumab+prednisone (constant dose) v Tocilizumab+prednisone (tapering dose)
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Number of subjects included in analysis |
259
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Analysis specification |
Pre-specified
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Analysis type |
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P-value |
= 0.021 | ||||||||||||
Method |
Cochran-Mantel-Haenszel | ||||||||||||
Parameter type |
Relative Risk | ||||||||||||
Point estimate |
0.833
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
0.714 | ||||||||||||
upper limit |
0.972 |
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End point title |
Change from baseline in clinical disease activity index (CDAI) at Week 24 | ||||||||||||
End point description |
Comparison between participants who continued versus tapered prednisone in Clinical Disease Activity Index (CDAI) score.
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End point type |
Secondary
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End point timeframe |
Baseline and Week 24
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Statistical analysis title |
Least Square Means | ||||||||||||
Comparison groups |
Tocilizumab+prednisone (tapering dose) v Tocilizumab+prednisone (constant dose)
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Number of subjects included in analysis |
259
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Analysis specification |
Pre-specified
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Analysis type |
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P-value |
= 0.006 | ||||||||||||
Method |
ANCOVA | ||||||||||||
Parameter type |
Least Square Means | ||||||||||||
Point estimate |
2.342
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
0.661 | ||||||||||||
upper limit |
4.023 |
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End point title |
Percentage of participants with >=1 flare | ||||||||||||
End point description |
Percentage of participants with >=1 flare
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End point type |
Secondary
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End point timeframe |
24 weeks
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No statistical analyses for this end point |
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End point title |
Percentage of participants with >=1 administration of flare rescue medication | ||||||||||||
End point description |
The proportion of participants with at least one administration of RA flare rescue medication.
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End point type |
Secondary
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End point timeframe |
Randomization to 24 weeks
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No statistical analyses for this end point |
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End point title |
Time to first administration of flare rescue medication | ||||||||||||
End point description |
Time of onset of first administration of RA flare rescue medication since randomization date
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End point type |
Secondary
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End point timeframe |
Randomization to 24 weeks
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No statistical analyses for this end point |
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End point title |
Number of administrations of flare rescue medication | |||||||||||||||||||||||||||
End point description |
Proportion of participants who received courses of RA flare rescue medication by number of courses received.
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End point type |
Secondary
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End point timeframe |
Randomization to 24 weeks
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No statistical analyses for this end point |
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End point title |
Cumulative prednisone exposure (dose) | |||||||||||||||||||||
End point description |
In Post-randomization prednisone arm, Cumulative dose = (number of capsules taken during week 1 to 4 * 1 mg) + (3/4 * number of capsules taken during week 5 to 8 * 1 mg) + (1/2 * number of capsules taken during week 9 to 12 * 1 mg) + (1/4 * number of capsules taken during week 13 to 16 * 1 mg). In continued arm, cumulative dose = (1/4 * number of capsule taken * 5 mg). Cumulative prednisone dose is defined as cumulative blinded prednisone + cumulative flare rescue prednisone.
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End point type |
Secondary
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End point timeframe |
Randomization to 24 weeks
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No statistical analyses for this end point |
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End point title |
Percentage of participants who maintain LDA (DAS28 ESR score <=3.2) or remission (DAS28 ESR score <2.6) and the percentage of participants who maintain the baseline disease activity level | |||||||||||||||||||||||||||
End point description |
The proportion of participants who maintained LDA and the proportion of participants who maintained the baseline disease activity level at Week 24. LDA was defined as DAS28 ESR score <= 3.2. Remission was defined as DAS28 ESR score <= 2.6. Participants who maintained the baseline activity was defined as DAS28-ESR at Week 24 <= DAS28-ESR at baseline.
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End point type |
Secondary
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End point timeframe |
Randomization to Week 24
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No statistical analyses for this end point |
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End point title |
Percentage of participants who permanently discontinue study treatment due to insufficient flare control | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
24 weeks
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No statistical analyses for this end point |
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End point title |
Change from baseline in simplified disease activity index (SDAI) at Week 24 | ||||||||||||
End point description |
The SDAI is the numerical sum of five outcome parameters: tender and swollen joint count (based on a 28-joint assessment), patient and physician global assessment of disease activity [visual analogue scale (VAS) 0-10 cm] and level of C-reactive protein (mg/dl, normal <1 mg/dl).
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End point type |
Secondary
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End point timeframe |
Randomization to Week 24
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Statistical analysis title |
Least Square Means | ||||||||||||
Comparison groups |
Tocilizumab+prednisone (tapering dose) v Tocilizumab+prednisone (constant dose)
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Number of subjects included in analysis |
259
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Analysis specification |
Pre-specified
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Analysis type |
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P-value |
= 0.009 | ||||||||||||
Method |
ANCOVA | ||||||||||||
Parameter type |
Least Square Means | ||||||||||||
Point estimate |
2.264
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
0.574 | ||||||||||||
upper limit |
3.953 |
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End point title |
Time to first RA flare | ||||||||||||
End point description |
The mean time of onset for the first RA flare since randomization.
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End point type |
Secondary
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End point timeframe |
Randomization to 24 weeks
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No statistical analyses for this end point |
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End point title |
Number of RA flares | ||||||||||||||||||||||||
End point description |
Number of visits with RA flares reported.
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End point type |
Secondary
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End point timeframe |
Randomization to 24 weeks
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No statistical analyses for this end point |
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End point title |
Changes from baseline in American College of Rheumatology (ACR) core set components at Week 24: Swollen 66 Joint Counts | ||||||||||||
End point description |
Count of swollen joints based upon 66 assessed joints.
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End point type |
Secondary
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End point timeframe |
Baseline to Week 24
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No statistical analyses for this end point |
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End point title |
Changes from baseline in American College of Rheumatology (ACR) core set components at Week 24: Tender 68 Joint Counts | ||||||||||||
End point description |
Count of tender joints based on 68 assessed joints.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline to Week 24
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Changes from baseline in American College of Rheumatology (ACR) core set components at Week 24: Patient's Assessment of Pain | ||||||||||||
End point description |
Scored on a Visual Analogue Scale (VAS) from 0 to 100 mm.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline to Week 24
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Changes from baseline in American College of Rheumatology (ACR) core set components at Week 24: Patient’s global assessment of disease activity | ||||||||||||
End point description |
Scored on a Visual Analogue Scale (VAS) from 0 to 10 cm.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline to Week 24
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Changes from baseline in American College of Rheumatology (ACR) core set components at Week 24: Physician’s Global Assessment of Disease Activity | ||||||||||||
End point description |
Scored on a Visual Analogue Scale (VAS) from 0 to 10 cm.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline to Week 24
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Changes from baseline in American College of Rheumatology (ACR) core set components at Week 24: Health Assessment Questionnaire–Disability Index (HAQ-DI) | ||||||||||||
End point description |
|||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline to Week 24
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Changes from baseline in American College of Rheumatology (ACR) core set components at Week 24: High Sensitivity C-Reactive Protein (hsCRP) | ||||||||||||
End point description |
|||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline to Week 24
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Changes from baseline in American College of Rheumatology (ACR) core set components at Week 24: Erythrocyte Sedimentation Rate (ESR) | ||||||||||||
End point description |
|||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline to Week 24
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Changes from baseline in Rheumatoid Arthritis Impact of Disease (RAID) Final score | ||||||||||||
End point description |
The RAID is a participant-completed questionnaire specific for RA consisting of a 1-10 rating for pain, functional disability, fatigue, sleep, physical well-being, emotional well-being and coping. Scores are weighted to produce a final numerical result.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline and Week 24
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||
End point title |
Changes from baseline in Work Productivity and Activity Impairment Questionnaire: Specific Health Problem (WPAI:SHP) score | ||||||||||||||||||||||||
End point description |
The WPAI:SHP is a 6-item questionnaire evaluating the effect of the underlying disease or condition on the participant’s ability to work and perform regular activities
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
Baseline and Week 24
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse events information
|
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Timeframe for reporting adverse events |
Randomization to Week 28
|
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Assessment type |
Non-systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
|
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
20.1
|
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Reporting groups
|
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Reporting group title |
Tocilizumab+prednisone (constant dose)
|
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Reporting group description |
Participants will receive tocilizumab at a dose of 162 milligram (mg) once a week subcutaneously; and prednisone at a dose of 5 milligram per day (mg/day) or matching placebo orally for 24 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Tocilizumab+prednisone (tapering dose)
|
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Reporting group description |
Participants will receive tocilizumab at a dose of 162 milligram (mg) once a week subcutaneously; and prednisone at a dose of 5 milligram per day (mg/day) with 1 mg decrements every 4 weeks or matching placebo orally for 24 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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|
|||
Substantial protocol amendments (globally) |
|||
Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
05 Jun 2015 |
Open-label prednisone tablets were to be offered during the 4 weeks preceding
randomization for patients in both tracks and provided for the treatment of any flare
following randomization (during the 24-week Tapering Phase); To facilitate the conduct and analysis of NSAIDs use, NSAID average use was captured as mean daily intake by considering the number of days on which NSAIDs had been taken during a period of interest (at screening, Week 12, and Week 24);Increasing the dose of NSAIDs during a flare was discouraged to minimize any confounding effect of NSAID use; In order to minimize screen failures due to temporary ailments or abnormalities, patients could be re-screened or re-tested, depending on the inclusion/exclusion criteria they failed, if authorized by the Sponsor; Timing of assessments of immunogenicity was clarified so that immunogenicity
sampling was event-driven and therefore only patients who experienced anaphylaxis or other hypersensitivity reaction were evaluated at the time of the event and 8 weeks after, as part of standard immunogenicity sampling protocol. |
||
22 Jun 2016 |
Amendment based on requests from the iDMC, investigator feedback, updated internal guidance and definitions, newly identified errata and updates to the IB. |
||
Interruptions (globally) |
|||
Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |