Clinical Trial Results:
A Randomized, Double-blind, Parallel, Placebo-controlled Study Assessing the Efficacy and Safety of Sarilumab Added to Non-biologic DMARD Therapy in Patients With Rheumatoid Arthritis Who Are Inadequate Responders to or Intolerant of TNF-α Antagonists
|
Summary
|
|
EudraCT number |
2011-003538-16 |
Trial protocol |
LT CZ HU ES DE PT GR AT IT SK PL |
Global end of trial date |
23 Mar 2015
|
|
Results information
|
|
Results version number |
v2(current) |
This version publication date |
10 Sep 2017
|
First version publication date |
07 Apr 2016
|
Other versions |
v1 |
Version creation reason |
|
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
|
|||
|
Trial identification
|
|||
Sponsor protocol code |
EFC10832
|
||
|
Additional study identifiers
|
|||
ISRCTN number |
- | ||
US NCT number |
NCT01709578 | ||
WHO universal trial number (UTN) |
U1111-1115-8466 | ||
|
Sponsors
|
|||
Sponsor organisation name |
Sanofi aventis recherche & développement
|
||
Sponsor organisation address |
1 avenue Pierre Brossolette,, Chilly-Mazarin, France, 91380
|
||
Public contact |
Trial Transparency Team, Sanofi aventis recherche & développement, Contact-US@sanofi.com
|
||
Scientific contact |
Trial Transparency Team, Sanofi aventis recherche & développement, Contact-US@sanofi.com
|
||
|
Paediatric regulatory details
|
|||
Is trial part of an agreed paediatric investigation plan (PIP) |
No
|
||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
|
Results analysis stage
|
|||
Analysis stage |
Final
|
||
Date of interim/final analysis |
22 Apr 2015
|
||
Is this the analysis of the primary completion data? |
No
|
||
Global end of trial reached? |
Yes
|
||
Global end of trial date |
23 Mar 2015
|
||
Was the trial ended prematurely? |
No
|
||
|
General information about the trial
|
|||
Main objective of the trial |
To demonstrate that sarilumab added to non-biologic disease modifying anti-rheumatic drugs (DMARDs) was effective in reducing the signs and symptoms at Week 24 and improving physical function at Week 12 in subjects with active rheumatoid arthritis (RA) who were inadequate responders to or intolerant of tumor necrosis factor alpha (TNF-α) antagonists.
|
||
Protection of trial subjects |
Subjects were fully informed of all pertinent aspects of the clinical trial as well as the possibility to discontinue at any time in language and terms appropriate for the subject and considering the local culture. During the course of the trial, subjects were provided with individual subject cards indicating the nature of the trial the subject is participating, contact details and any information needed in the event of a medical emergency. Collected personal data and human biological samples were processed in compliance with the Sanofi Aventis Group Personal Data Protection Charter ensuring that the Group abides by the laws governing personal data protection in force in all countries in which it operates.
|
||
Background therapy |
Subjects continued to receive regular treatment with at least one of the permitted background therapies that included hydroxychloroquine, methotrexate, sulfasalazine, leflunomide which were dispensed according to the local practice. | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
29 Oct 2012
|
||
Long term follow-up planned |
No
|
||
Independent data monitoring committee (IDMC) involvement? |
Yes
|
||
|
Population of trial subjects
|
|||
Number of subjects enrolled per country |
|||
Country: Number of subjects enrolled |
Canada: 2
|
||
Country: Number of subjects enrolled |
Chile: 3
|
||
Country: Number of subjects enrolled |
Colombia: 19
|
||
Country: Number of subjects enrolled |
Czech Republic: 13
|
||
Country: Number of subjects enrolled |
Ecuador: 11
|
||
Country: Number of subjects enrolled |
Germany: 28
|
||
Country: Number of subjects enrolled |
Greece: 2
|
||
Country: Number of subjects enrolled |
Guatemala: 13
|
||
Country: Number of subjects enrolled |
Hungary: 3
|
||
Country: Number of subjects enrolled |
Israel: 2
|
||
Country: Number of subjects enrolled |
Italy: 2
|
||
Country: Number of subjects enrolled |
Korea, Republic of: 2
|
||
Country: Number of subjects enrolled |
Lithuania: 5
|
||
Country: Number of subjects enrolled |
Mexico: 62
|
||
Country: Number of subjects enrolled |
New Zealand: 10
|
||
Country: Number of subjects enrolled |
Peru: 49
|
||
Country: Number of subjects enrolled |
Poland: 59
|
||
Country: Number of subjects enrolled |
Portugal: 1
|
||
Country: Number of subjects enrolled |
Russian Federation: 15
|
||
Country: Number of subjects enrolled |
Spain: 18
|
||
Country: Number of subjects enrolled |
Taiwan: 1
|
||
Country: Number of subjects enrolled |
Turkey: 1
|
||
Country: Number of subjects enrolled |
Ukraine: 8
|
||
Country: Number of subjects enrolled |
United States: 147
|
||
Country: Number of subjects enrolled |
Argentina: 52
|
||
Country: Number of subjects enrolled |
Australia: 5
|
||
Country: Number of subjects enrolled |
Brazil: 13
|
||
Worldwide total number of subjects |
546
|
||
EEA total number of subjects |
131
|
||
Number of subjects enrolled per age group |
|||
In utero |
0
|
||
Preterm newborn - gestational age < 37 wk |
0
|
||
Newborns (0-27 days) |
0
|
||
Infants and toddlers (28 days-23 months) |
0
|
||
Children (2-11 years) |
0
|
||
Adolescents (12-17 years) |
0
|
||
Adults (18-64 years) |
456
|
||
From 65 to 84 years |
88
|
||
85 years and over |
2
|
||
|
|||||||||||||||||||||||||||||||||||||
|
Recruitment
|
|||||||||||||||||||||||||||||||||||||
Recruitment details |
The study was conducted at 240 centres in 27 countries. A total of 1224 subjects were screened between 29 October 2012 and 7 August 2014, of whom 546 subjects were randomized and 678 were screen failures. Screen failures were mainly due to failure to meet inclusion criteria. | ||||||||||||||||||||||||||||||||||||
|
Pre-assignment
|
|||||||||||||||||||||||||||||||||||||
Screening details |
Subjects were randomized 1:1:1 (placebo q2w: sarilumab 150 mg q2w: sarilumab 200 mg q2w) via a centralized randomization system using an interactive voice response system stratified by region and number of previous anti-tumor necrosis factor therapy (1 versus >1). | ||||||||||||||||||||||||||||||||||||
|
Period 1
|
|||||||||||||||||||||||||||||||||||||
Period 1 title |
Overall Study (overall period)
|
||||||||||||||||||||||||||||||||||||
Is this the baseline period? |
Yes | ||||||||||||||||||||||||||||||||||||
Allocation method |
Randomised - controlled
|
||||||||||||||||||||||||||||||||||||
Blinding used |
Double blind | ||||||||||||||||||||||||||||||||||||
Roles blinded |
Subject, Investigator, Carer, Assessor | ||||||||||||||||||||||||||||||||||||
|
Arms
|
|||||||||||||||||||||||||||||||||||||
Are arms mutually exclusive |
Yes
|
||||||||||||||||||||||||||||||||||||
|
Arm title
|
Placebo q2w | ||||||||||||||||||||||||||||||||||||
Arm description |
Placebo matched to sarilumab once every 2 weeks (q2w) was added to one or a combination of the non-biologic DMARD for 24 weeks. | ||||||||||||||||||||||||||||||||||||
Arm type |
Placebo | ||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Placebo
|
||||||||||||||||||||||||||||||||||||
Investigational medicinal product code |
|||||||||||||||||||||||||||||||||||||
Other name |
|||||||||||||||||||||||||||||||||||||
Pharmaceutical forms |
Solution for injection in pre-filled syringe
|
||||||||||||||||||||||||||||||||||||
Routes of administration |
Subcutaneous use
|
||||||||||||||||||||||||||||||||||||
Dosage and administration details |
Placebo matched to sarilumab administered subcutaneously in abdomen, thigh or upper arm.
|
||||||||||||||||||||||||||||||||||||
|
Arm title
|
Sarilumab 150 mg q2w | ||||||||||||||||||||||||||||||||||||
Arm description |
Sarilumab 150 mg q2w was added to one or a combination of the non-biologic DMARD for 24 weeks. | ||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Sarilumab
|
||||||||||||||||||||||||||||||||||||
Investigational medicinal product code |
SAR153191
|
||||||||||||||||||||||||||||||||||||
Other name |
REGN88
|
||||||||||||||||||||||||||||||||||||
Pharmaceutical forms |
Solution for injection in pre-filled syringe
|
||||||||||||||||||||||||||||||||||||
Routes of administration |
Subcutaneous use
|
||||||||||||||||||||||||||||||||||||
Dosage and administration details |
Sarilumab 150 mg administered subcutaneously in abdomen, thigh or upper arm.
|
||||||||||||||||||||||||||||||||||||
|
Arm title
|
Sarilumab 200 mg q2w | ||||||||||||||||||||||||||||||||||||
Arm description |
Sarilumab 200 mg q2w was added to one or a combination of the non-biologic DMARD for 24 weeks. | ||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Sarilumab
|
||||||||||||||||||||||||||||||||||||
Investigational medicinal product code |
SAR153191
|
||||||||||||||||||||||||||||||||||||
Other name |
REGN88
|
||||||||||||||||||||||||||||||||||||
Pharmaceutical forms |
Solution for injection in pre-filled syringe
|
||||||||||||||||||||||||||||||||||||
Routes of administration |
Subcutaneous use
|
||||||||||||||||||||||||||||||||||||
Dosage and administration details |
Sarilumab 200 mg administered subcutaneously in abdomen, thigh or upper arm.
|
||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Baseline characteristics reporting groups
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo q2w
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Placebo matched to sarilumab once every 2 weeks (q2w) was added to one or a combination of the non-biologic DMARD for 24 weeks. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Sarilumab 150 mg q2w
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Sarilumab 150 mg q2w was added to one or a combination of the non-biologic DMARD for 24 weeks. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Sarilumab 200 mg q2w
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Sarilumab 200 mg q2w was added to one or a combination of the non-biologic DMARD for 24 weeks. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||
|
End points reporting groups
|
|||
Reporting group title |
Placebo q2w
|
||
Reporting group description |
Placebo matched to sarilumab once every 2 weeks (q2w) was added to one or a combination of the non-biologic DMARD for 24 weeks. | ||
Reporting group title |
Sarilumab 150 mg q2w
|
||
Reporting group description |
Sarilumab 150 mg q2w was added to one or a combination of the non-biologic DMARD for 24 weeks. | ||
Reporting group title |
Sarilumab 200 mg q2w
|
||
Reporting group description |
Sarilumab 200 mg q2w was added to one or a combination of the non-biologic DMARD for 24 weeks. | ||
|
|||||||||||||||||
End point title |
Percentage of Subjects Who Achieved at Least 20% Improvement in the American College of Rheumatology (ACR20) Criteria at Week 24 | ||||||||||||||||
End point description |
ACR responses were assessed with a composite rating scale of the American College of Rheumatology that includes 7 variables: tender joint count (TJC); swollen joint count (SJC); levels of an acute phase reactant (C-reactive Protein levels [CRP]); subject's assessment of pain; subject's global assessment of disease activity; physician's global assessment of disease activity; subject's assessment of physical function (HAQ-DI). ACR20 is defined as achieving at least 20% improvement in both TJC and SJC, and at least 20% improvement in at least 3 of the 5 other assessments of the ACR. Analysis was performed on intent-to-treat (ITT) population included all randomized subjects.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Week 24
|
||||||||||||||||
|
|||||||||||||||||
Statistical analysis title |
Placebo q2w vs Sarilumab 150 mg q2w | ||||||||||||||||
Statistical analysis description |
A hierarchical testing procedure was used to control type I error rate at 0.05 and handle multiple endpoint analyses. Testing was then performed sequentially in the order the endpoints were reported. The hierarchical testing sequence continued only when previous endpoint was statistically significant at 0.025 level.
|
||||||||||||||||
Comparison groups |
Placebo q2w v Sarilumab 150 mg q2w
|
||||||||||||||||
Number of subjects included in analysis |
362
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
superiority | ||||||||||||||||
P-value |
< 0.0001 [1] | ||||||||||||||||
Method |
Mantel-Haenszel | ||||||||||||||||
Parameter type |
Odds ratio (OR) | ||||||||||||||||
Point estimate |
2.711
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
1.73 | ||||||||||||||||
upper limit |
4.247 | ||||||||||||||||
| Notes [1] - Threshold for significance at 0.025 level |
|||||||||||||||||
Statistical analysis title |
Placebo q2w vs Sarilumab 200 mg q2w | ||||||||||||||||
Statistical analysis description |
Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
|
||||||||||||||||
Comparison groups |
Placebo q2w v Sarilumab 200 mg q2w
|
||||||||||||||||
Number of subjects included in analysis |
365
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
superiority | ||||||||||||||||
P-value |
< 0.0001 [2] | ||||||||||||||||
Method |
Mantel-Haenszel | ||||||||||||||||
Parameter type |
Odds ratio (OR) | ||||||||||||||||
Point estimate |
3.284
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
2.108 | ||||||||||||||||
upper limit |
5.115 | ||||||||||||||||
| Notes [2] - Threshold for significance at 0.025 level |
|||||||||||||||||
|
|||||||||||||||||
End point title |
Change From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 12 | ||||||||||||||||
End point description |
Physical function was assessed by HAQ-DI. It consisted of at least 2 questions per category, subject reported ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week rated on a 4-point scale where 0 = no difficulty; 1 = some difficulty; 2 = much difficulty; 3 = unable to do. Overall score was the sum of category scores and divided by the number of categories answered, ranging from 0 to 3, where 0 = no disability and 3 = unable to do, high-dependency disability. Least-squares (LS) means and standard errors (SE) at Week 12 were obtained from a mixed-effect model with repeated measures (MMRM) with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline HAQ-DI as a covariate. Analysis was performed on ITT population. Number of subjects analyzed = number of subjects with HAQ-DI assessment at both baseline and Week 12.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Baseline, Week 12
|
||||||||||||||||
|
|||||||||||||||||
Statistical analysis title |
Placebo q2w vs Sarilumab 150 mg q2w | ||||||||||||||||
Statistical analysis description |
Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
|
||||||||||||||||
Comparison groups |
Placebo q2w v Sarilumab 150 mg q2w
|
||||||||||||||||
Number of subjects included in analysis |
335
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
superiority | ||||||||||||||||
P-value |
= 0.0007 [3] | ||||||||||||||||
Method |
Mixed models analysis | ||||||||||||||||
Parameter type |
LS mean difference | ||||||||||||||||
Point estimate |
-0.202
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
-0.318 | ||||||||||||||||
upper limit |
-0.086 | ||||||||||||||||
| Notes [3] - Threshold for significance at 0.025 level |
|||||||||||||||||
Statistical analysis title |
Placebo q2w vs Sarilumab 200 mg q2w | ||||||||||||||||
Statistical analysis description |
Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
|
||||||||||||||||
Comparison groups |
Placebo q2w v Sarilumab 200 mg q2w
|
||||||||||||||||
Number of subjects included in analysis |
341
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
superiority | ||||||||||||||||
P-value |
= 0.0004 [4] | ||||||||||||||||
Method |
Mixed models analysis | ||||||||||||||||
Parameter type |
LS Mean Difference | ||||||||||||||||
Point estimate |
-0.21
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
-0.325 | ||||||||||||||||
upper limit |
-0.095 | ||||||||||||||||
| Notes [4] - Threshold for significance at 0.025 level |
|||||||||||||||||
|
|||||||||||||||||
End point title |
Change From Baseline in Disease Activity Score for 28 Joints -C-Reactive Protein (DAS28-CRP) Score at Week 24 | ||||||||||||||||
End point description |
DAS28 is a composite score of 4 variables:TJC (28 joints);SJC (28 joints);General health (GH) assessment by the subject assessed from the ACR (RA) core set questionnaire (subject global assessment) in 100 mm visual analog scale(VAS). Marker of inflammation assessed by the high sensitivity C-reactive protein (hs-CRP) in mg/L. The DAS28 score indicate the current disease activity of the RA. DAS28 total score ranges from 2-10. A DAS28 score above 5.1 means high disease activity, score below 3.2 indicates low disease activity and a score below 2.6 means disease remission. LS means and SE at Week 24 by MMRM with treatment, region, number of previous anti-TNFs,visit,and treatment-by-visit interaction as fixed effects and baseline DAS28-CRP score as a covariate. Analysis was performed on ITT population. Number of subjects analyzed=number of subjects with DAS28-CRP Score at both baseline and Week 24.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Baseline, Week 24
|
||||||||||||||||
|
|||||||||||||||||
Statistical analysis title |
Placebo q2w vs Sarilumab 150 mg q2w | ||||||||||||||||
Statistical analysis description |
Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
|
||||||||||||||||
Comparison groups |
Placebo q2w v Sarilumab 150 mg q2w
|
||||||||||||||||
Number of subjects included in analysis |
225
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
superiority | ||||||||||||||||
P-value |
< 0.0001 [5] | ||||||||||||||||
Method |
Mixed models analysis | ||||||||||||||||
Parameter type |
LS Mean Difference | ||||||||||||||||
Point estimate |
-0.971
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
-1.283 | ||||||||||||||||
upper limit |
-0.658 | ||||||||||||||||
| Notes [5] - Threshold for significance at 0.025 level |
|||||||||||||||||
Statistical analysis title |
Placebo q2w vs Sarilumab 200 mg q2w | ||||||||||||||||
Statistical analysis description |
Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
|
||||||||||||||||
Comparison groups |
Placebo q2w v Sarilumab 200 mg q2w
|
||||||||||||||||
Number of subjects included in analysis |
235
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
superiority | ||||||||||||||||
P-value |
< 0.0001 [6] | ||||||||||||||||
Method |
Mixed models analysis | ||||||||||||||||
Parameter type |
LS Mean Difference | ||||||||||||||||
Point estimate |
-1.444
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
-1.752 | ||||||||||||||||
upper limit |
-1.135 | ||||||||||||||||
| Notes [6] - Threshold for significance at 0.025 level |
|||||||||||||||||
|
|||||||||||||||||
End point title |
Percentage of Subjects Achieving ACR50 Criteria at Week 24 | ||||||||||||||||
End point description |
ACR responses were assessed with a composite rating scale of the American College of Rheumatology that includes 7 variables: TJC; SJC; levels of an acute phase reactant (CRP level); subject’s assessment of pain; subject’s global assessment of disease activity; physician’s global assessment of disease activity; subject’s assessment of physical function (HAQ-DI). ACR50 is defined as achieving at least 50% improvement in both TJC and SJC, and at least 50% improvement in at least 3 of the 5 other assessments of the ACR. Analysis was performed on ITT population.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Week 24
|
||||||||||||||||
|
|||||||||||||||||
Statistical analysis title |
Placebo q2w vs Sarilumab 150 mg q2w | ||||||||||||||||
Statistical analysis description |
Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
|
||||||||||||||||
Comparison groups |
Placebo q2w v Sarilumab 150 mg q2w
|
||||||||||||||||
Number of subjects included in analysis |
362
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
superiority | ||||||||||||||||
P-value |
< 0.0001 [7] | ||||||||||||||||
Method |
Mantel-Haenszel | ||||||||||||||||
Parameter type |
Odds ratio (OR) | ||||||||||||||||
Point estimate |
2.958
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
1.764 | ||||||||||||||||
upper limit |
4.959 | ||||||||||||||||
| Notes [7] - Threshold for significance at 0.025 level |
|||||||||||||||||
Statistical analysis title |
Placebo q2w vs Sarilumab 200 mg q2w | ||||||||||||||||
Statistical analysis description |
Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
|
||||||||||||||||
Comparison groups |
Placebo q2w v Sarilumab 200 mg q2w
|
||||||||||||||||
Number of subjects included in analysis |
365
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
superiority | ||||||||||||||||
P-value |
< 0.0001 [8] | ||||||||||||||||
Method |
Mantel-Haenszel | ||||||||||||||||
Parameter type |
Odds ratio (OR) | ||||||||||||||||
Point estimate |
3.374
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
2.045 | ||||||||||||||||
upper limit |
5.566 | ||||||||||||||||
| Notes [8] - Threshold for significance was 0.025 level |
|||||||||||||||||
|
|||||||||||||||||
End point title |
Percentage of Subjects Achieving ACR70 Criteria at Week 24 | ||||||||||||||||
End point description |
ACR responses were assessed with a composite rating scale of the American College of Rheumatology that includes 7 variables: TJC; SJC; levels of an acute phase reactant (CRP level); subject’s assessment of pain; subject’s global assessment of disease activity; physician’s global assessment of disease activity; subject’s assessment of physical function (HAQ-DI). ACR70 is defined as achieving at least 70% improvement in both TJC and SJC, and at least 70% improvement in at least 3 of the 5 other assessments of the ACR. Analysis was performed on ITT population.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Week 24
|
||||||||||||||||
|
|||||||||||||||||
Statistical analysis title |
Placebo q2w vs Sarilumab 150 mg q2w | ||||||||||||||||
Statistical analysis description |
Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
|
||||||||||||||||
Comparison groups |
Placebo q2w v Sarilumab 150 mg q2w
|
||||||||||||||||
Number of subjects included in analysis |
362
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
superiority | ||||||||||||||||
P-value |
= 0.0002 [9] | ||||||||||||||||
Method |
Mantel-Haenszel | ||||||||||||||||
Parameter type |
Odds ratio (OR) | ||||||||||||||||
Point estimate |
3.607
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
1.774 | ||||||||||||||||
upper limit |
7.332 | ||||||||||||||||
| Notes [9] - Threshold for significance at 0.025 level |
|||||||||||||||||
Statistical analysis title |
Placebo q2w vs Sarilumab 200 mg q2w | ||||||||||||||||
Statistical analysis description |
Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
|
||||||||||||||||
Comparison groups |
Placebo q2w v Sarilumab 200 mg q2w
|
||||||||||||||||
Number of subjects included in analysis |
365
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
superiority | ||||||||||||||||
P-value |
= 0.0056 [10] | ||||||||||||||||
Method |
Mantel-Haenszel | ||||||||||||||||
Parameter type |
Odds ratio (OR) | ||||||||||||||||
Point estimate |
2.653
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
1.308 | ||||||||||||||||
upper limit |
5.383 | ||||||||||||||||
| Notes [10] - Threshold for significance at 0.025 level |
|||||||||||||||||
|
|||||||||||||||||
End point title |
Percentage of Subjects Achieving Clinical Remission Score (DAS28-CRP) <2.6 at Week 24 | ||||||||||||||||
End point description |
DAS28 is a composite score that includes 4 variables: TJC (based on 28 joints); SJC (based on 28 joints); GH by the subject assessed from the ACR rheumatoid arthritis core set questionnaire (subject global assessment) in 100 mm VAS; marker of inflammation assessed by hs-CRP in mg/L. The DAS28 provides a number indicating the current activity of the RA. DAS28 total score ranges from 2-10. A DAS28 score above 5.1 means high disease activity, whereas a DAS28 score below 3.2 indicates low disease activity and a DAS28 score below 2.6 means disease remission. Analysis was performed on ITT population.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Week 24
|
||||||||||||||||
|
|||||||||||||||||
Statistical analysis title |
Placebo q2w vs Sarilumab 150 mg q2w | ||||||||||||||||
Statistical analysis description |
Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
|
||||||||||||||||
Comparison groups |
Placebo q2w v Sarilumab 150 mg q2w
|
||||||||||||||||
Number of subjects included in analysis |
362
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
superiority | ||||||||||||||||
P-value |
< 0.0001 [11] | ||||||||||||||||
Method |
Mantel-Haenszel | ||||||||||||||||
Parameter type |
Odds ratio (OR) | ||||||||||||||||
Point estimate |
4.622
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
2.339 | ||||||||||||||||
upper limit |
9.132 | ||||||||||||||||
| Notes [11] - Threshold for significance at 0.025 level |
|||||||||||||||||
Statistical analysis title |
Copy of Placebo q2w vs Sarilumab 200 mg q2w | ||||||||||||||||
Statistical analysis description |
Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
|
||||||||||||||||
Comparison groups |
Placebo q2w v Sarilumab 200 mg q2w
|
||||||||||||||||
Number of subjects included in analysis |
365
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
superiority | ||||||||||||||||
P-value |
< 0.0001 [12] | ||||||||||||||||
Method |
Mantel-Haenszel | ||||||||||||||||
Parameter type |
Odds ratio (OR) | ||||||||||||||||
Point estimate |
5.801
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
2.948 | ||||||||||||||||
upper limit |
11.413 | ||||||||||||||||
| Notes [12] - Threshold for significance at 0.025 level |
|||||||||||||||||
|
|||||||||||||||||
End point title |
Change From Baseline in Clinical Disease Activity Index (CDAI) at Week 24 | ||||||||||||||||
End point description |
CDAI is a composite index constructed to measure clinical remission in RA that does not include a laboratory test, and is a numerical summation of 4 components: TJC (28 joints), SJC (28 joints), Subject’s Global Assessment of Disease Activity VAS (in cm), and Physician’s Global Assessment of Disease VAS (in cm). Total scores ranges from 0 to 76 with a negative change in CDAI score indicating an improvement in disease activity and a positive change in score indicating a worsening of disease activity. LS means and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline CDAI as a covariate. Analysis was performed on ITT population. Number of subjects analyzed=number of subjects with CDAI assessment at both baseline and Week 24.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Baseline, Week 24
|
||||||||||||||||
|
|||||||||||||||||
Statistical analysis title |
Placebo q2w vs Sarilumab 150 mg q2w | ||||||||||||||||
Statistical analysis description |
Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
|
||||||||||||||||
Comparison groups |
Placebo q2w v Sarilumab 150 mg q2w
|
||||||||||||||||
Number of subjects included in analysis |
227
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
superiority | ||||||||||||||||
P-value |
< 0.0001 [13] | ||||||||||||||||
Method |
Mixed models analysis | ||||||||||||||||
Parameter type |
LS Mean Difference | ||||||||||||||||
Point estimate |
-7.306
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
-10.444 | ||||||||||||||||
upper limit |
-4.167 | ||||||||||||||||
| Notes [13] - Threshold for significance at 0.025 level |
|||||||||||||||||
Statistical analysis title |
Placebo q2w vs Sarilumab 200 mg q2w | ||||||||||||||||
Statistical analysis description |
Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
|
||||||||||||||||
Comparison groups |
Placebo q2w v Sarilumab 200 mg q2w
|
||||||||||||||||
Number of subjects included in analysis |
236
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
superiority | ||||||||||||||||
P-value |
< 0.0001 [14] | ||||||||||||||||
Method |
Mixed models analysis | ||||||||||||||||
Parameter type |
LS Mean Difference | ||||||||||||||||
Point estimate |
-9.727
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
-12.833 | ||||||||||||||||
upper limit |
-6.622 | ||||||||||||||||
| Notes [14] - Threshold for significance at 0.025 level |
|||||||||||||||||
|
|||||||||||||||||
End point title |
Change From Baseline in HAQ-DI at Week 24 | ||||||||||||||||
End point description |
Physical function was assessed by HAQ-DI. It consisted of at least 2 questions per category, subject reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week rated on a 4-point scale where 0 = no difficulty; 1 = some difficulty; 2 = much difficulty; 3 = unable to do. Overall score was computed as the sum of category scores and divided by the number of categories answered, ranging from 0 to 3, where 0 = no disability and 3 = unable to do, high-dependency disability. LS means and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline HAQ-DI as a covariate. Analysis was performed on ITT population. Number of subjects analyzed = number of subjects with HAQ-DI assessment at both baseline and Week 24.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Baseline, Week 24
|
||||||||||||||||
|
|||||||||||||||||
Statistical analysis title |
Placebo q2w vs Sarilumab 150 mg q2w | ||||||||||||||||
Statistical analysis description |
Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
|
||||||||||||||||
Comparison groups |
Placebo q2w v Sarilumab 150 mg q2w
|
||||||||||||||||
Number of subjects included in analysis |
228
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
superiority | ||||||||||||||||
P-value |
= 0.0078 [15] | ||||||||||||||||
Method |
Mixed models analysis | ||||||||||||||||
Parameter type |
LS Mean Difference | ||||||||||||||||
Point estimate |
-0.183
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
-0.318 | ||||||||||||||||
upper limit |
-0.048 | ||||||||||||||||
| Notes [15] - Threshold for significance was 0.025 level |
|||||||||||||||||
Statistical analysis title |
Placebo q2w vs Sarilumab 200 mg q2w | ||||||||||||||||
Statistical analysis description |
Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
|
||||||||||||||||
Comparison groups |
Placebo q2w v Sarilumab 200 mg q2w
|
||||||||||||||||
Number of subjects included in analysis |
237
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
superiority | ||||||||||||||||
P-value |
= 0.0004 [16] | ||||||||||||||||
Method |
Mixed models analysis | ||||||||||||||||
Parameter type |
LS Mean Difference | ||||||||||||||||
Point estimate |
-0.242
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
-0.376 | ||||||||||||||||
upper limit |
-0.109 | ||||||||||||||||
| Notes [16] - Threshold for significance was 0.025 level |
|||||||||||||||||
|
|||||||||||||||||
End point title |
Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Physical Component Summary Scores (PCS) at Week 24 | ||||||||||||||||
End point description |
SF-36 a 36-item questionnaire measuring health-related quality of life (HRQL) covering 2 summary measures: PCS and mental component summary (MCS). The SF-36 consists of 8 subscales. The PCS had 4 subscales: physical function, role limitations due to physical problems, pain, and general health perception. The MCS had 4 subscales: vitality, social function, role limitations due to emotional problems, and mental health. Reporting on subscale that have between 2-6 choices per item using Likert-type responses. Summations of item scores give the subscale scores, which range from 0 to 100; zero= worst HRQL, 100=best HRQL. Higher scores indicate better health and well-being. LS mean and SE at Week 24 by MMRM with treatment,region,number of previous anti TNFs,visit,and treatment-by-visit interaction as fixed effects and baseline SF-36 PCS as a covariate. Analysis was performed on ITT population. Number of subjects analyzed = subjects with SF-36 PCS assessment at both baseline and Week 24.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Baseline, Week 24
|
||||||||||||||||
|
|||||||||||||||||
Statistical analysis title |
Placebo q2w vs Sarilumab 150 mg q2w | ||||||||||||||||
Statistical analysis description |
Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
|
||||||||||||||||
Comparison groups |
Placebo q2w v Sarilumab 150 mg q2w
|
||||||||||||||||
Number of subjects included in analysis |
222
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
superiority | ||||||||||||||||
P-value |
= 0.0004 [17] | ||||||||||||||||
Method |
Mixed models analysis | ||||||||||||||||
Parameter type |
LS Mean Difference | ||||||||||||||||
Point estimate |
3.25
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
1.45 | ||||||||||||||||
upper limit |
5.049 | ||||||||||||||||
| Notes [17] - Threshold for significance at 0.025 level |
|||||||||||||||||
Statistical analysis title |
Placebo q2w vs Sarilumab 200 mg q2w | ||||||||||||||||
Statistical analysis description |
Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
|
||||||||||||||||
Comparison groups |
Placebo q2w v Sarilumab 200 mg q2w
|
||||||||||||||||
Number of subjects included in analysis |
233
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
superiority | ||||||||||||||||
P-value |
< 0.0001 [18] | ||||||||||||||||
Method |
Mixed models analysis | ||||||||||||||||
Parameter type |
LS Mean Difference | ||||||||||||||||
Point estimate |
4.075
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
2.305 | ||||||||||||||||
upper limit |
5.846 | ||||||||||||||||
| Notes [18] - Threshold for significance at 0.025 level |
|||||||||||||||||
|
|||||||||||||||||
End point title |
Change From Baseline in SF-36 MCS at Week 24 | ||||||||||||||||
End point description |
SF-36 is 36-item questionnaire measuring HRQL covering PCS and MCS. The SF-36 is of 8 subscales. The PCS is represented by 4 subscales: physical function, role limitations due to physical problems, pain, and general health perception. The MCS is represented by 4 subscales: vitality, social function, role limitations due to emotional problems, and mental health. Subjects self-report on items in a subscale that have between 2-6 choices per item using Likert-type responses. Summations of item scores of the same subscale give the subscale scores, which range from 0to100; zero= worst HRQL, 100=best HRQL. Higher scores indicate better health and well-being. LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs,visit and treatment-by-visit interaction as fixed effects and baseline SF-36 MCS as a covariate. Analysis was performed on ITT population. Number of subjects analyzed=subjects with SF-36 MCS assessment at both baseline and Week 24.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Baseline, Week 24
|
||||||||||||||||
|
|||||||||||||||||
Statistical analysis title |
Placebo q2w vs Sarilumab 150 mg q2w | ||||||||||||||||
Statistical analysis description |
Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
|
||||||||||||||||
Comparison groups |
Placebo q2w v Sarilumab 150 mg q2w
|
||||||||||||||||
Number of subjects included in analysis |
222
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
superiority | ||||||||||||||||
P-value |
= 0.2026 [19] | ||||||||||||||||
Method |
Mixed models analysis | ||||||||||||||||
Parameter type |
LS Mean Difference | ||||||||||||||||
Point estimate |
1.515
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
-0.818 | ||||||||||||||||
upper limit |
3.848 | ||||||||||||||||
| Notes [19] - Threshold for significance at 0.025 level |
|||||||||||||||||
Statistical analysis title |
Placebo q2w vs Sarilumab 200 mg q2w | ||||||||||||||||
Statistical analysis description |
Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).
|
||||||||||||||||
Comparison groups |
Placebo q2w v Sarilumab 200 mg q2w
|
||||||||||||||||
Number of subjects included in analysis |
233
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
superiority | ||||||||||||||||
P-value |
= 0.0854 [20] | ||||||||||||||||
Method |
Mixed models analysis | ||||||||||||||||
Parameter type |
LS Mean Difference | ||||||||||||||||
Point estimate |
2.013
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
-0.282 | ||||||||||||||||
upper limit |
4.309 | ||||||||||||||||
| Notes [20] - Threshold for significance at 0.025 level |
|||||||||||||||||
|
|||||||||||||||||
End point title |
Change From Baseline in the Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-fatigue) Score at Week 24 | ||||||||||||||||
End point description |
The FACIT-Fatigue is a 13-item questionnaire assessing fatigue where subjects scored each item on a 5-point scale (0-4): 0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, 4=very much. A total score ranging from 0 to 52. A higher score corresponded to a lower level of fatigue. A positive change from baseline score indicates an improvement. LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline FACIT-fatigue as a covariate. Analysis was performed on ITT population. Number of Subjects analyzed = number of subjects with FACIT-fatigue score assessment at both baseline and Week 24.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Baseline, Week 24
|
||||||||||||||||
|
|||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||
|
|||||||||||||||||
End point title |
Change From Baseline in Morning Stiffness VAS at Week 24 | ||||||||||||||||
End point description |
RA is associated with stiffness of joints, especially in the morning after prolonged stationery state. The degree of stiffness can be an indicator of disease severity. The severity of morning stiffness was assessed on a VAS scale from 0 mm (no problem) to 100 mm (major problem). LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline Morning Stiffness as a covariate. Analysis was performed on ITT population. Number of subjects analyzed = number of subjects with morning stiffness VAS assessment at both baseline and Week 24.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Baseline, Week 24
|
||||||||||||||||
|
|||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||
|
|||||||||||||||||
End point title |
Change From Baseline in Work Productivity Survey - Rheumatoid Arthritis (WPS-RA) at Week 24: Work Days Missed Due to RA | ||||||||||||||||
End point description |
The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on subject self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Number of work days missed in the last month by the subject was reported. LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate. Analysis was performed on ITT population. Number of subjects analyzed = subjects with WPS-RA individual items assessment at both baseline and Week 24.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Baseline, Week 24
|
||||||||||||||||
|
|||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||
|
|||||||||||||||||
End point title |
Change From Baseline in WPS-RA at Week 24: Days With Work Productivity Reduced by ≥ 50% Due to RA | ||||||||||||||||
End point description |
The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on subject self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Number of work days with reduced productivity by ≥ 50% in the last month by the subject was reported. LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate. Analysis was performed on ITT population. Number of subjects analyzed=subjects with WPS-RA individual items assessment at both baseline and Week 24.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Baseline, Week 24
|
||||||||||||||||
|
|||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||
|
|||||||||||||||||
End point title |
Change From Baseline in WPS-RA at Week 24: RA Interference With Work Productivity | ||||||||||||||||
End point description |
The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer administered and was based on subject self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Interference in the last month with work productivity is measured on a scale that ranges from 0 (no interference) to 10 (complete interference). LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate. Analysis was performed on ITT population. Number of subjects analyzed = subjects with WPS-RA individual items assessment at both baseline and Week 24.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Baseline, Week 24
|
||||||||||||||||
|
|||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||
|
|||||||||||||||||
End point title |
Change From Baseline in WPS-RA at Week 24: House Work Days Missed Due to RA | ||||||||||||||||
End point description |
The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on subject self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Number of days with no household work in the last month by the subject was reported. LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate. Analysis was performed on ITT population. Number of subjects analyzed = subjects with WPS-RA individual items assessment at both baseline and Week 24.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Baseline, Week 24
|
||||||||||||||||
|
|||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||
|
|||||||||||||||||
End point title |
Change From Baseline in WPS-RA at Week 24: Days With Household Work Productivity Reduced by ≥ 50% Due to RA | ||||||||||||||||
End point description |
The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on subject self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Number of days with reduced household work productivity by ≥ 50% in the last month by the subject was reported. LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate. Analysis was performed on ITT population. Number of subjects analyzed = subjects with WPS-RA individual items assessment at both baseline and Week 24.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Baseline, Week 24
|
||||||||||||||||
|
|||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||
|
|||||||||||||||||
End point title |
Change From Baseline in WPS-RA at Week 24: Days With Family/Social/Leisure Activities Missed Due to RA | ||||||||||||||||
End point description |
The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on subject self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Number of days missed of family/social/leisure activities in the last month by the subject was reported. LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.Analysis was performed on ITT population. Number of subjects analyzed = subjects with WPS-RA individual items assessment at both baseline and Week 24.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Baseline, Week 24
|
||||||||||||||||
|
|||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||
|
|||||||||||||||||
End point title |
Change From Baseline in WPS-RA at Week 24: Days With Outside Help Hired Due to RA | ||||||||||||||||
End point description |
The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on subject self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Number of days with outside help hired in the last month by the subject was reported. LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.Analysis was performed on ITT population. Number of subjects analyzed = subjects with WPS-RA individual items assessment at both baseline and Week 24.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Baseline, Week 24
|
||||||||||||||||
|
|||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||
|
|||||||||||||||||
End point title |
Change From Baseline in WPS-RA at Week 24: RA Interference With Household Work Productivity | ||||||||||||||||
End point description |
The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on subject self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). The RA interference in the last month with household work productivity was measured on a scale that ranges from 0 (no interference) to 10 (complete interference). LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate. Analysis was performed on ITT population. Number of subjects analyzed = subjects with WPS-RA individual items assessment at both baseline and Week 24.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Baseline, Week 24
|
||||||||||||||||
|
|||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||
|
|||||||||||||||||
End point title |
Change From Baseline in Rheumatoid Arthritis Impact of Disease (RAID) Scores at Week 24 | ||||||||||||||||
End point description |
RAID is a composite measure of the impact of RA on subjects that takes into account 7 domains: pain, functional disability, fatigue, physical and emotional well being, quality of sleep, and coping. The RAID is calculated based on 7 numerical rating scales (NRS) questions. Range of the final RAID value is 0-10 where 0= not affected, very good and 10 = most affected weighted and calculated with a total score range of 0 (not affected, very good) to 10 (most affected). A higher RAID value indicate worse status and lower indicate not affected. LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline RAID as a covariate. Analysis was performed on ITT population. Number of subjects analyzed = number of subjects with RAID score assessment at both baseline and Week 24.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Baseline, Week 24
|
||||||||||||||||
|
|||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||
|
|||||||||||||||||
End point title |
Change From Baseline in European Quality of Life-5 Dimension 3 Level (EQ-5D-3L) VAS Scores at Week 24 | ||||||||||||||||
End point description |
The EQ-5D-3L is a standardized, generic measure of health outcome. EQ-5D was designed for self-completion by subjects. The EQ-5D was specifically included to address concerns regarding the health economic impact of RA. The EQ-5D-3L comprises 5 questions on mobility, self-care, pain, usual activities, and psychological status with 3 possible answers for each item (1=no problem, 2=moderate problems, 3=severe problems) and a vertical VAS that allows the subjects to indicate their health state today that can range from 0 (worst imaginable) to 100 (best imaginable). LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline EQ-5D-3L Scores as a covariate. Analysis was performed on ITT population. Number of subjects analyzed = number of subjects with EQ-5D-3L score assessment at both baseline and Week 24.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Baseline, Week 24
|
||||||||||||||||
|
|||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||
|
|||||||||||||||||||||||||||||
End point title |
Percentage of Subjects Achieving ACR20, ACR50 and ACR70 Criteria at Week 12 | ||||||||||||||||||||||||||||
End point description |
ACR responses were assessed with a composite rating scale of the American College of Rheumatology that includes 7 variables: TJC; SJC; levels of an acute phase reactant (CRP level); subject’s assessment of pain; subject’s global assessment of disease activity; physician’s global assessment of disease activity; subject’s assessment of physical function (HAQ-DI). ACR20 is defined as achieving at least 20% improvement in both TJC and SJC, and at least 20% improvement in at least 3 of the 5 other assessments of the ACR. ACR50 is defined as achieving at least 50% improvement in both TJC and SJC, and at least 50% improvement in at least 3 of the 5 other assessments of the ACR. ACR70 is defined as achieving at least 70% improvement in both TJC and SJC, and at least 70% improvement in at least 3 of the 5 other assessments of the ACR. Analysis was performed on ITT population.
|
||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||
End point timeframe |
Week 12
|
||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||
|
|||||||||||||||||
End point title |
Changes From Baseline in Disease Activity Score (DAS) 28 at Week 12 | ||||||||||||||||
End point description |
DAS28 is a composite score that includes 4 variables: TJC (based on 28 joints); SJC (based on 28 joints); GH by the subject assessed from the ACR rheumatoid arthritis core set questionnaire (subject global assessment) in 100 mm VAS; marker of inflammation assessed by hs-CRP in mg/L. The DAS28 provides a number indicating the current activity of the RA. DAS28 total score ranges from 2-10. A DAS28 score above 5.1 means high disease activity, whereas a DAS28 score below 3.2 indicates low disease activity and a DAS28 score below 2.6 means disease remission. LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline DAS score as a covariate. Analysis was performed on ITT population. Number of subjects analyzed = number of subjects with DAS28- Score assessment at both baseline and Week 12.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Baseline, Week 12
|
||||||||||||||||
|
|||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||
|
|||||||||||||||||
End point title |
Percentage of Subjects Achieving Clinical Remission Score (DAS28-CRP) <2.6 at Week 12 | ||||||||||||||||
End point description |
DAS28 was a composite score that includes 4 variables: TJC (based on 28 joints); SJC (based on 28 joints); GH by the subject assessed from the ACR rheumatoid arthritis core set questionnaire (subject global assessment) in 100 mm VAS; marker of inflammation assessed by hs-CRP in mg/L. The DAS28 provides a number indicating the current activity of the RA. DAS28 total score ranges from 2-10. A DAS28 score above 5.1 means high disease activity, whereas a DAS28 score below 3.2 indicates low disease activity and a DAS28 score below 2.6 means disease remission. Analysis was performed on ITT population.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Baseline, Week 12
|
||||||||||||||||
|
|||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||
|
|||||||||||||||||||||||||
End point title |
Change From Baseline in SF-36 at Week 12 | ||||||||||||||||||||||||
End point description |
SF-36 a 36-item questionnaire measuring health-related quality of life (HRQL) covering 2 summary measures: PCS and mental component summary (MCS). The SF-36 consists of 8 subscales. The PCS had 4 subscales: physical function, role limitations due to physical problems, pain, and general health perception. The MCS had 4 subscales: vitality, social function, role limitations due to emotional problems, and mental health. Reporting on subscale that have between 2-6 choices per item using Likert-type responses. Summations of item scores give the subscale scores, which range from 0 to 100; zero= worst HRQL, 100=best HRQL. Higher scores indicate better health and well-being. LS mean and SE at Week 12 by MMRM with treatment,region,number of previous anti TNFs,visit,and treatment-by-visit interaction as fixed effects and baseline SF-36 (PCS) as a covariate. Analysis was performed on ITT population. Number of subjects analyzed = subjects with SF-36 PCS assessment at both baseline and Week 12.
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
Baseline, Week 12
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||
|
|||||||||||||||||
End point title |
Change From Baseline in WPS-RA at Week 12: Work Days Missed Due to RA | ||||||||||||||||
End point description |
The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on subject self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Number of work days missed in the last month by the subject was reported. LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate. Analysis was performed on ITT population. Number of subjects analyzed = subjects with WPS-RA individual items assessment at both baseline and Week 12.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Baseline, Week 12
|
||||||||||||||||
|
|||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||
|
|||||||||||||||||
End point title |
Change From Baseline in WPS-RA at Week 12: Days With Work Productivity Reduced by ≥ 50% Due to RA | ||||||||||||||||
End point description |
The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on subject self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Number of work days with reduced productivity by ≥ 50% in the last month by the subject was reported. LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate. Analysis was performed on ITT population. Number of subjects analyzed = subjects with WPS-RA individual items assessment at both baseline and Week 12.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Baseline, Week 12
|
||||||||||||||||
|
|||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||
|
|||||||||||||||||
End point title |
Change From Baseline in WPS-RA at Week 12: RA Interference With Work Productivity | ||||||||||||||||
End point description |
The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on subject self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Interference in the last month with work productivity was measured on a scale that ranges from 0 (no interference) to 10 (complete interference). LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate. Analysis was performed on ITT population. Number of subjects analyzed = subjects with WPS-RA individual items assessment at both baseline and Week 12.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Baseline, Week 12
|
||||||||||||||||
|
|||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||
|
|||||||||||||||||
End point title |
Change From Baseline in WPS-RA at Week 12: House Work Days Missed Due to RA | ||||||||||||||||
End point description |
The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on subject self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Number of days with no household work in the last month by the subject was reported. LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate. Analysis was performed on ITT population. Number of subjects analyzed = subjects with WPS-RA individual items assessment at both baseline and Week 12.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Baseline, Week 12
|
||||||||||||||||
|
|||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||
|
|||||||||||||||||
End point title |
Change From Baseline in WPS-RA at Week 12: Days With Household Work Productivity Reduced by ≥ 50% Due to RA | ||||||||||||||||
End point description |
The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on subject self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Number of days with reduced household work productivity by ≥ 50% in the last month by the subject was reported. LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate. Analysis was performed on ITT population. Number of subjects analyzed = subjects with WPS-RA individual items assessment at both baseline and Week 12.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Baseline, Week 12
|
||||||||||||||||
|
|||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||
|
|||||||||||||||||
End point title |
Change From Baseline in WPS-RA at Week 12: Days With Family/Social/Leisure Activities Missed Due to RA | ||||||||||||||||
End point description |
The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on subject self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Number of days missed of family/social/leisure activities in the last month in the last month by the subject was reported. LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate. Analysis was performed on ITT population. Number of subjects analyzed = subjects with WPS-RA individual items assessment at both baseline and Week 12.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Baseline, Week 12
|
||||||||||||||||
|
|||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||
|
|||||||||||||||||
End point title |
Change From Baseline in WPS-RA at Week 12: Days With Outside Help Hired Due to RA | ||||||||||||||||
End point description |
The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on subject self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Number of days with outside help hired in the last month by the subject was reported. LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate. Analysis was performed on ITT population. Number of subjects analyzed = subjects with WPS-RA individual items assessment at both baseline and Week 12.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Baseline, Week 12
|
||||||||||||||||
|
|||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||
|
|||||||||||||||||
End point title |
Change From Baseline in WPS-RA at Week 12: RA Interference With Household Work Productivity | ||||||||||||||||
End point description |
The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on subject self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). The RA interference in the last month with household work productivity was measured on a scale that ranges from 0 (no interference) to 10 (complete interference). LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate. Analysis was performed on ITT population. Number of subjects analyzed = subjects with WPS-RA individual items assessment at both baseline and Week 12.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Baseline, Week 12
|
||||||||||||||||
|
|||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||
|
|||||||||||||||||
End point title |
Change From Baseline in the FACIT-fatigue at Week 12 | ||||||||||||||||
End point description |
The FACIT-Fatigue is a 13-item questionnaire assessing fatigue where subjects scored each item on a 5-point scale (0-4): 0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, 4=very much. A total score ranging from 0 to 52. A higher score corresponded to a lower level of fatigue. A positive change from baseline score indicates an improvement. LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline FACIT-fatigue as a covariate. Analysis was performed on ITT population. Number of Subjects analyzed = number of subjects with FACIT-fatigue score assessment at both baseline and Week 12.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Baseline, Week 12
|
||||||||||||||||
|
|||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||
|
|||||||||||||||||
End point title |
Change From Baseline in EQ-5D-3L VAS Scores at Week 12 | ||||||||||||||||
End point description |
The EQ-5D-3L is a standardized, generic measure of health outcome. EQ-5D was designed for self-completion by subjects. The EQ-5D was specifically included to address concerns regarding the health economic impact of RA. The EQ-5D-3L comprises 5 questions on mobility, self-care, pain, usual activities, and psychological status with 3 possible answers for each item (1=no problem, 2=moderate problems, 3=severe problems) and a vertical VAS that allows the subjects to indicate their health state today that can range from 0 (worst imaginable) to 100 (best imaginable). LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline EQ-5D-3L Scores as a covariate. Analysis was performed on ITT population. Number of subjects analyzed = number of subjects with EQ-5D-3L score assessment at both baseline and Week 12.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Baseline, Week 12
|
||||||||||||||||
|
|||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||
|
|||||||||||||||||
End point title |
Change From Baseline in RAID Scores at Week 12 | ||||||||||||||||
End point description |
RAID is a composite measure of the impact of RA on subjects that takes into account 7 domains: pain, functional disability, fatigue, physical and emotional well being, quality of sleep, and coping. The RAID is calculated based on 7 NRS questions. Range of the final RAID value is 0-10 where 0= not affected, very good and 10 = most affected weighted and calculated with a total score range of 0 (not affected, very good) to 10 (most affected). A higher RAID value indicate worse status and lower indicate not affected. LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline RAID as a covariate. Analysis was performed on ITT population. Number of subjects analyzed = number of subjects with RAID score assessment at both baseline and Week 12.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Baseline, Week 12
|
||||||||||||||||
|
|||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||
|
|||||||||||||||||||||||||||||||||
End point title |
Change From Baseline in Individual ACR Components - TJC and SJC at Week 12 and Week 24 | ||||||||||||||||||||||||||||||||
End point description |
ACR components were: TJC, SJC, physician global VAS, subject global VAS, pain VAS,HAQ-DI & CRP. 68 joints were assessed for tenderness (TJC scoring 0-68) and 66 joints for swelling (SJC scoring 0-66). The 66 SJC evaluated the following joints: temporomandibular, sternoclavicular, acromioclavicular, shoulder, elbow, wrist, metacarpophalangeal, interphalangeal of thumb, distal interphalangeal, proximal interphalangeal, knee, ankle mortise, ankle tarsus, metatarsophalangeal, interphalangeal of great toe, and proximal/distal interphalangeal of the toes. The TJC examined hip joints, in addition to the joints assessed for SJC. Increase in number of tender joints/swollen joints indicated severity. LS mean and SE at Week 12 & 24 by MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline ACR components as a covariate. ITT population. Here ’n’ signifies number of subjects with available data for specified category.
|
||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||
End point timeframe |
Baseline, Week 12 and Week 24
|
||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||
End point title |
Change From Baseline in Individual ACR Component - Physician Global VAS, Subject Global VAS and Pain VAS at Week 12 and Week 24 | ||||||||||||||||||||||||||||||||||||||||
End point description |
ACR components were: TJC, SJC, physician global VAS, subject global VAS, pain VAS, HAQ-DI & CRP. Physician global VAS & subject global VAS was done by 100 mm non-anchored VAS, from no arthritis (0) activity to maximal arthritis (100) activity. Pain VAS by 100 mm VAS ranging from 0 "no pain" to 100 "worst pain". LS mean and SE at Week 12 & 24 by MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline ACR components as a covariate. Analysis was performed on ITT population. Here ’n’ signifies number of subjects with available data for specified category.
|
||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Baseline, Week 12 and Week 24
|
||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||
End point title |
Change From Baseline in Individual ACR Component - CRP Level at Week 12 and Week 24 | ||||||||||||||||||||||||
End point description |
ACR components were: TJC, SJC, physician global VAS, subject global VAS, pain VAS, HAQ-DI & CRP. An elevated CRP level was considered a non-specific "marker" for RA. A reduction level indicates improvement. LS mean and SE at Week 12 & 24 by MMRM with treatment, region, number of previous anti- TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline ACR components as a covariate. Analysis was performed on ITT population. Here ’n’ signifies number of subjects with available data for specified category.
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
Baseline, Week 12 and Week 24
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||
|
|||||||||||||||||||||||||
End point title |
Change From Baseline in Individual ACR Component - HAQ-DI at Week 12 and Week 24 | ||||||||||||||||||||||||
End point description |
ACR components were: TJC, SJC, physician global VAS, subject global VAS, pain VAS, HAQ-DI & CRP. HAQ-DI consisted of at least 2 questions per category, subject reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week rated on a 4-point scale where 0 = no difficulty; 1 = some difficulty; 2 = much difficulty; 3 = unable to do. Overall score was computed as the sum of category scores and divided by the number of categories answered, ranging from 0 to 3, where 0 = no disability and 3 = unable to do, high dependency disability. LS mean and SE at Week 12 & 24 by MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline ACR components as a covariate. Analysis was performed on ITT population. Here ’n’ signifies number of subjects with available data for specified category.
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
Baseline, Week 12 and Week 24
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Adverse events information
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 30) regardless of seriousness or relationship to investigational product.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse event reporting additional description |
Reported adverse events are treatment emergent adverse events that is AEs that developed/worsened and death during ‘on treatment period’ (time from the first dose injection of study drug to the end of follow up period). Safety population included all subjects from randomized population who received at least 1 dose or part of a dose of study drug.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Dictionary used for adverse event reporting
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
17.1
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo q2w
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Placebo matched to sarilumab q2w was added to one or a combination of the non-biologic DMARD for 24 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Sarilumab 150 mg q2w
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Sarilumab 150 mg q2w was added to one or a combination of the non-biologic DMARD for 24 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Sarilumab 200 mg q2w
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Sarilumab 200 mg q2w was added to one or a combination of the non-biologic DMARD for 24 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||
Substantial protocol amendments (globally) |
|||
| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
06 Sep 2012 |
• To implement new safety measures to prevent the administration of sarilumab to subjects at risk for development of severe thrombocytopenia (<100 000/mm3) and grade 3/grade 4 neutropenia (based on NCI Common Terminology Criteria for Adverse Events [CTCAE]).
• To delete the Visit 3 (Week2) sampling time point for “genetic RNA” or “RNA for sequencing” .
• To remove the open-label rescue therapy arm within this study (EFC10832) and give subject qualifying for rescue therapy the opportunity to directly enroll into the parallel ongoing long-term safety study (LTS11210) to receive open-label rescue therapy with sarilumab.
• To replace the partial EQ-5D-3L (EuroQol) instrument with the original complete instrument
• To add an additional exclusion criterion related to interstitial lung disease.
• To clarify instructions that for any occurrence of a serious adverse event (SAE) and for any occurrence of an adverse event of special interest (AESI) with immediate notification, investigators must report such events to the monitoring team within 24 hours of knowledge of them, and send any follow up data related to the event to the monitoring team also within 24 hours of knowledge.
• To clarify in the Clinical Trial Summary and text related to categorical safety analyses, cardiovascular (CV) events, and analyses of the laboratory data, vital signs data and electrocardiogram data. |
||
03 Apr 2013 |
• To update text related to dosage regimen of methotrexate in the Clinical Trial Summary.
• To clarify the general accepted adult age limit and treatment related to dyslipidemia.
• To update study medication storage conditions.
• Updated text relating to treatment accountability and compliance and treatment kit disposal.
• To remove text related to description of an open treatment arm with sarilumab that is no longer part of the study design in relevant sections.
• To update text related to handling of subject for temporary and permanent treatment discontinuation.
• To update safety reporting instructions in relevant sections. |
||
29 Oct 2014 |
• To modify the analyses for the co-primary endpoint related to change in physical function as measured by the HAQ-DI and replace the co-primary endpoint related to change in physical function as measured by the HAQ-DI from the “average of change from baseline in the HAQ-DI from week 8 to Week 24” to the co-primary endpoint of “the change from baseline in the HAQ-DI at
Week 12” This was done to ensure a robust analysis was performed at a time point where the amount of missing data was minimal and where there was a sufficiently long period of treatment with study drug to permit a correct assessment of effect on physical function.
• To remove the reference related to the Committee for Medicinal Products for Human Use (CHMP) guidelines for blood pressure measurement as the current instructions in the protocol for blood pressure measurement primarily reflected practical considerations and were to serve as generic guidance to ensure consistency.
• To replace the acronym “ANC (absolute neutrophil count)” with “neutrophil count,” in relevant sections.
• To remove references to the bioanalytical assay and related analyses for “serum sarilumab-IL-6Rα complex (bound sarilumab)” as this assay was not performed for this study population. |
||
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 | |||
