Clinical Trial Results:
A multi-center, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of Certolizumab Pegol in combination with Methotrexate for inducing and sustaining clinical response in the treatment of DMARD-Naïve adults with early active Rheumatoid Arthritis
Summary
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EudraCT number |
2011-001729-25 |
Trial protocol |
DE IE HU ES CZ AT SE NL IT GB |
Global end of trial date |
10 Sep 2015
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Results information
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Results version number |
v4(current) |
This version publication date |
17 Sep 2016
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First version publication date |
24 Jul 2015
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Other versions |
v1 , v2 , v3 |
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
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Trial identification
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Sponsor protocol code |
RA0055 Period 2
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01521923 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
UCB Pharma SA
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Sponsor organisation address |
Allée de la Recherche 60, Brussels, Belgium, B-1070
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Public contact |
Clinical Trial Registries and Results Disclosure, UCB BIOSCIENCES GmbH, clinicaltrials@ucb.com
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Scientific contact |
Clinical Trial Registries and Results Disclosure, UCB BIOSCIENCES GmbH, clinicaltrials@ucb.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
13 Oct 2015
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
10 Sep 2015
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The primary objective is to demonstrate that both CZP + MTX dosing frequencies (the standard maintenance dose CZP 200 mg every 2 weeks + MTX and the reduced frequency maintenance dose CZP 200 mg every 4 weeks + MTX) are superior to PBO + MTX in maintaining subjects in LDA at Week 104
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Protection of trial subjects |
Not applicable
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Background therapy |
Not applicable | ||
Evidence for comparator |
Not applicable | ||
Actual start date of recruitment |
25 Jan 2012
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Spain: 11
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Country: Number of subjects enrolled |
Sweden: 6
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Country: Number of subjects enrolled |
Switzerland: 2
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Country: Number of subjects enrolled |
United Kingdom: 10
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Country: Number of subjects enrolled |
United States: 71
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Country: Number of subjects enrolled |
Argentina: 16
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Country: Number of subjects enrolled |
Australia: 19
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Country: Number of subjects enrolled |
Belgium: 19
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Country: Number of subjects enrolled |
Colombia: 13
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Country: Number of subjects enrolled |
Czech Republic: 26
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Country: Number of subjects enrolled |
France: 2
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Country: Number of subjects enrolled |
Germany: 40
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Country: Number of subjects enrolled |
Hungary: 16
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Country: Number of subjects enrolled |
Ireland: 3
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Country: Number of subjects enrolled |
Italy: 5
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Country: Number of subjects enrolled |
Mexico: 14
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Country: Number of subjects enrolled |
Netherlands: 4
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Country: Number of subjects enrolled |
Poland: 77
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Country: Number of subjects enrolled |
Romania: 3
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Worldwide total number of subjects |
357
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EEA total number of subjects |
222
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
312
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From 65 to 84 years |
45
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85 years and over |
0
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Recruitment
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Recruitment details |
This study started to enroll subjects in January 2012. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Pre-assignment
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Screening details |
Participant Flow refers to the Safety Set 2 (SS2) which consists of all subjects randomized into Period 1 who had received at least 1 dose of study medication (CZP/PBO) in Period 2. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Period 1
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Period 1 title |
Period 2 (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Roles blinded |
Subject, Investigator, Carer | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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PBO+MTX / PBO+MTX | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Arm description |
Placebo (PBO) + Methotrexate (MTX) in Period 1 1 syringe PBO every 2 Weeks + MTX in Period 2 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Arm type |
Placebo non-comparator | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Methotrexate
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Investigational medicinal product code |
MTX
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Other name |
Trexan
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
A dose of at least 15 mg per Week had to be taken to remain in the study. MTX was given every week from Week 52 onwards until Week 103
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Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
PBO
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Other name |
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Pharmaceutical forms |
Solution for injection in pre-filled syringe
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Subcutaneous injections every 2 Weeks or every 4 Weeks
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Arm title
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CZP+MTX / PBO+MTX | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Arm description |
Certolizumab pegol (CZP) 200 mg Q2W + Methotrexate (MTX) in Period 1 1 syringe PBO every 2 Weeks + MTX in Period 2 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Arm type |
Placebo | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Certolizumab pegol
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Investigational medicinal product code |
CZP
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Other name |
Cimzia
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Pharmaceutical forms |
Solution for injection in pre-filled syringe
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Subcutaneous injections: 200 mg every 2 Weeks or every 4 Weeks
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Investigational medicinal product name |
Methotrexate
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Investigational medicinal product code |
MTX
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Other name |
Trexan
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
A dose of at least 15 mg per Week had to be taken to remain in the study. MTX was given every week from Week 52 onwards until Week 103
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Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
PBO
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Other name |
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Pharmaceutical forms |
Solution for injection in pre-filled syringe
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Subcutaneous injections every 2 Weeks or every 4 Weeks
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Arm title
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CZP+MTX / CZP Q4W+MTX | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Arm description |
Certolizumab pegol (CZP) 200 mg Q2W + Methotrexate (MTX) in Period 1 1 syringe 200 mg Certolizumab pegol (CZP) every 4 Weeks/ 1 syringe Placebo (PBO) every 4 Weeks (CZP and PBO administration to be staggered 2 weeks apart to maintain blind) + MTX in Period 2 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Methotrexate
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Investigational medicinal product code |
MTX
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Other name |
Trexan
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
A dose of at least 15 mg per Week had to be taken to remain in the study. MTX was given every week from Week 52 onwards until Week 103
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Investigational medicinal product name |
Certolizumab pegol
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Investigational medicinal product code |
CZP
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Other name |
Cimzia
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Pharmaceutical forms |
Solution for injection in pre-filled syringe
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Subcutaneous injections: 200 mg every 2 Weeks or every 4 Weeks
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Arm title
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CZP+MTX / CZP Q2W+MTX | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Arm description |
Certolizumab pegol (CZP) 200 mg Q2W + Methotrexate (MTX) in Period 1 1 syringe 200 mg Certolizumab pegol (CZP) every 2 Weeks + MTX in Period 2 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Methotrexate
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Investigational medicinal product code |
MTX
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Other name |
Trexan
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
A dose of at least 15 mg per Week had to be taken to remain in the study. MTX was given every week from Week 52 onwards until Week 103
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Investigational medicinal product name |
Certolizumab pegol
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Investigational medicinal product code |
CZP
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Other name |
Cimzia
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Pharmaceutical forms |
Solution for injection in pre-filled syringe
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Subcutaneous injections: 200 mg every 2 Weeks or every 4 Weeks
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Baseline characteristics reporting groups
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Reporting group title |
PBO+MTX / PBO+MTX
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Reporting group description |
Placebo (PBO) + Methotrexate (MTX) in Period 1 1 syringe PBO every 2 Weeks + MTX in Period 2 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
CZP+MTX / PBO+MTX
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Reporting group description |
Certolizumab pegol (CZP) 200 mg Q2W + Methotrexate (MTX) in Period 1 1 syringe PBO every 2 Weeks + MTX in Period 2 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
CZP+MTX / CZP Q4W+MTX
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Reporting group description |
Certolizumab pegol (CZP) 200 mg Q2W + Methotrexate (MTX) in Period 1 1 syringe 200 mg Certolizumab pegol (CZP) every 4 Weeks/ 1 syringe Placebo (PBO) every 4 Weeks (CZP and PBO administration to be staggered 2 weeks apart to maintain blind) + MTX in Period 2 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
CZP+MTX / CZP Q2W+MTX
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Reporting group description |
Certolizumab pegol (CZP) 200 mg Q2W + Methotrexate (MTX) in Period 1 1 syringe 200 mg Certolizumab pegol (CZP) every 2 Weeks + MTX in Period 2 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
PBO+MTX / PBO+MTX
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Reporting group description |
Placebo (PBO) + Methotrexate (MTX) in Period 1 1 syringe PBO every 2 Weeks + MTX in Period 2 | ||
Reporting group title |
CZP+MTX / PBO+MTX
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Reporting group description |
Certolizumab pegol (CZP) 200 mg Q2W + Methotrexate (MTX) in Period 1 1 syringe PBO every 2 Weeks + MTX in Period 2 | ||
Reporting group title |
CZP+MTX / CZP Q4W+MTX
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Reporting group description |
Certolizumab pegol (CZP) 200 mg Q2W + Methotrexate (MTX) in Period 1 1 syringe 200 mg Certolizumab pegol (CZP) every 4 Weeks/ 1 syringe Placebo (PBO) every 4 Weeks (CZP and PBO administration to be staggered 2 weeks apart to maintain blind) + MTX in Period 2 | ||
Reporting group title |
CZP+MTX / CZP Q2W+MTX
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Reporting group description |
Certolizumab pegol (CZP) 200 mg Q2W + Methotrexate (MTX) in Period 1 1 syringe 200 mg Certolizumab pegol (CZP) every 2 Weeks + MTX in Period 2 | ||
Subject analysis set title |
CZP+MTX / PBO+MTX (Full Analysis Set)
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
Certolizumab pegol (CZP) 200 mg Q2W + Methotrexate (MTX) in Period 1
1 syringe PBO every 2 Weeks + MTX in Period 2
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Subject analysis set title |
CZP+MTX / CZP Q4W+MTX (Full Analysis Set)
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
Certolizumab pegol (CZP) 200 mg Q2W + Methotrexate (MTX) in Period 1
1 syringe 200 mg Certolizumab pegol (CZP) every 4 Weeks/ 1 syringe Placebo (PBO) every 4 Weeks (CZP and PBO administration to be staggered 2 weeks apart to maintain blind) + MTX in Period 2
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Subject analysis set title |
CZP+MTX / CZP Q2W+MTX (Full Analysis Set)
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
Certolizumab pegol (CZP) 200 mg Q2W + Methotrexate (MTX) in Period 1
1 syringe 200 mg Certolizumab pegol (CZP) every 2 Weeks + MTX in Period 2
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Subject analysis set title |
CZP+MTX / PBO+MTX (Radiographic Set)
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Certolizumab pegol (CZP) 200 mg Q2W + Methotrexate (MTX) in Period 1
1 syringe PBO every 2 Weeks + MTX in Period 2
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Subject analysis set title |
CZP+MTX / CZP Q4W+MTX (Radiographic Set)
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Certolizumab pegol (CZP) 200 mg Q2W + Methotrexate (MTX) in Period 1
1 syringe 200 mg Certolizumab pegol (CZP) every 4 Weeks/ 1 syringe Placebo (PBO) every 4 Weeks (CZP and PBO administration to be staggered 2 weeks apart to maintain blind) + MTX in Period 2
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Subject analysis set title |
CZP+MTX / CZP Q2W+MTX (Radiographic Set)
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Certolizumab pegol (CZP) 200 mg Q2W + Methotrexate (MTX) in Period 1
1 syringe 200mg Certolizumab pegol (CZP) every 2 Weeks + MTX in Period 2
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End point title |
Percentage of subjects with Disease Activity Score [Erythrocyte Sedimentation Rate] (DAS28 [ESR]) <= 3.2 at Week 104 in RA0055 Period 2 without flaring | ||||||||||||||||||||
End point description |
This Outcome Measure includes all subjects that have a DAS28 [ESR] <= 3.2 from the start of RA0055 Period 2 (Week 52 of RA0055 Period 1) to Week 104 in RA0055 Period 2 without flaring.
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End point type |
Primary
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End point timeframe |
Week 104 in RA0055 Period 2
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||||||||||||||||||||
|
|||||||||||||||||||||
Statistical analysis title |
Statistical Analysis 1 | ||||||||||||||||||||
Statistical analysis description |
In order to control the overall study-wise Type I error rate at 5 %, hypothesis testing was performed in a hierarchical order beginning with the CZP standard maintenance dosing (200 mg Q2W) + MTX group vs the CZP stopped dosing (PBO) + MTX group. If this analysis was statistically significant at the alpha = 0.05 level, an additional comparison of the CZP reduced frequency dosing (200 mg Q4W) + MTX group vs the CZP stopped dosing + MTX group was performed with testing at the alpha = 0.05 level
|
||||||||||||||||||||
Comparison groups |
CZP+MTX / PBO+MTX (Full Analysis Set) v CZP+MTX / CZP Q2W+MTX (Full Analysis Set)
|
||||||||||||||||||||
Number of subjects included in analysis |
163
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||||
P-value |
= 0.112 | ||||||||||||||||||||
Method |
Regression, Logistic | ||||||||||||||||||||
Parameter type |
Odds ratio (OR) | ||||||||||||||||||||
Point estimate |
1.719
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
0.881 | ||||||||||||||||||||
upper limit |
3.354 | ||||||||||||||||||||
Statistical analysis title |
Statistical Analysis 2 | ||||||||||||||||||||
Statistical analysis description |
In order to control the overall study-wise Type I error rate at 5 %, hypothesis testing was performed in a hierarchical order. A hierarchical test procedure was applied to protect the Overall significance level for the multiplicity of endpoints. Hypothesis testing was performed in the following predefined order, each at a 2-sided 95 % alpha level
|
||||||||||||||||||||
Comparison groups |
CZP+MTX / PBO+MTX (Full Analysis Set) v CZP+MTX / CZP Q4W+MTX (Full Analysis Set)
|
||||||||||||||||||||
Number of subjects included in analysis |
205
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||||
P-value |
= 0.041 | ||||||||||||||||||||
Method |
Regression, Logistic | ||||||||||||||||||||
Parameter type |
Odds ratio (OR) | ||||||||||||||||||||
Point estimate |
1.889
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
1.026 | ||||||||||||||||||||
upper limit |
3.48 |
|
|||||||||||||||||||||
End point title |
Percentage of subjects with Disease Activity Score 28 [ESR] (DAS28 [ESR]) < 2.6 at Week 52 in previous study RA0055 Period 1 who maintain a DAS28 [ESR] < 2.6 from Week 52 in RA0055 Period 1 through Week 104 in RA0055 Period 2 without flaring | ||||||||||||||||||||
End point description |
DAS28[ESR] is calculated using the Tender Joint Count (TJC), Swollen Joint Count (SJC) Erythrocyte Sedimentation Rate (ESR in mm/hour), and the Patient's Global Assessment of Disease Activity - Visual Analog Scale (PtGADA-VAS in mm) using the following formula: 0.56 x √(TJC) + 0.28 x √(SJC) + 0.70 x lognat (ESR) + 0.014 x PtGADA, where 28 joints are examined and a lower score indicates less disease activity.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
From Week 52 in RA0055 Period 1 to Week 104 in RA0055 Period 2
|
||||||||||||||||||||
|
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Change from Baseline in previous study RA0055 Period 1 in modified Total Sharp Score (mTSS) to Week 104 in RA0055 Period 2 | ||||||||||||||||||||
End point description |
Van der Heijde modified Total Sharp Score (mTSS) is a methodology to assess the degree of joint damage by quantifying the extent of bone erosions and joint space narrowing for 64 and 52 joints, respectively, with higher scores representing greater damage.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
From Baseline (Week 0) in RA0055 Period 1 to Week 104 in RA0055 Period 2
|
||||||||||||||||||||
|
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Change from Week 52 in previous study RA0055 Period 1 in modified Total Sharp Score (mTSS) to Week 104 in RA0055 Period 2 | ||||||||||||||||||||
End point description |
Van der Heijde modified Total Sharp Score (mTSS) is a methodology to assess the degree of joint damage by quantifying the extent of bone erosions and joint space narrowing for 64 and 52 joints, respectively, with higher scores representing greater damage.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
From Week 52 in RA0055 Period 1 to Week 104 in RA0055 Period 2
|
||||||||||||||||||||
|
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Percentage of subjects with radiographic non-progression from Baseline in previous study RA0055 Period 1 to Week 104 in RA0055 Period 2 | ||||||||||||||||||||
End point description |
Radiographic nonprogression is defined as change in modified Total Sharp Score (mTSS) <= 0.5.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
From Baseline (Week 0) in RA0055 Period 1 to Week 104 in RA0055 Period 2
|
||||||||||||||||||||
|
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Percentage of subjects with radiographic non-progression from Week 52 in previous study RA0055 Period 1 to Week 104 in RA0055 Period 2 | ||||||||||||||||||||
End point description |
Radiographic nonprogression is defined as change in modified Total Sharp Score (mTSS) <= 0.5.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
From Week 52 in RA0055 Period 1 to Week 104 in RA0055 Period 2
|
||||||||||||||||||||
|
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Change from Baseline in previous study RA0055 Period 1 in the joint erosion score to Week 104 in RA0055 Period 2 | ||||||||||||||||||||
End point description |
Erosions were assessed in 16 locations per hand and 6 joints per foot. Erosions for each hand location were scored from 0 to 5, with 0 indicating no erosion. Scores 1 to 5 may have included combinations of discrete erosion(s) and/or large erosions. Erosions for each foot joint were scored from 0 to 10, with 0 indicating no erosions.
The maximum possible erosion score for all 32-hand joints was 160. The maximum possible erosion score for all 12 feet joints was 120. Thus, the maximum possible total erosion score for hands and feet was 280.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
From Baseline (Week 0) in RA0055 Period 1 to Week 104 in RA0055 Period 2
|
||||||||||||||||||||
|
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Change from Week 52 in previous study RA0055 Period 1 in the joint erosion score to Week 104 in RA0055 Period 2 | ||||||||||||||||||||
End point description |
Erosions were assessed in 16 locations per hand and 6 joints per foot. Erosions for each hand location were scored from 0 to 5, with 0 indicating no erosion. Scores 1 to 5 may have included combinations of discrete erosion(s) and/or large erosions. Erosions for each foot joint were scored from 0 to 10, with 0 indicating no erosions.
The maximum possible erosion score for all 32-hand joints was 160. The maximum possible erosion score for all 12 feet joints was 120. Thus, the maximum possible total erosion score for hands and feet was 280.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
From Week 52 in RA0055 Period 1 to Week 104 in RA0055 Period 2
|
||||||||||||||||||||
|
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Change from Baseline in previous study RA0055 Period 1 in the joint narrowing score to Week 104 in RA0055 Period 2 | ||||||||||||||||||||
End point description |
Joint space narrowing (JSN) was assessed in 15 locations per hand and 6 locations per foot. Joint space narrowing for each location was scored from 0 to 4, with 0 indicating no narrowing. The maximum possible score for JSN in all 30 hand joints was 120. The maximum possible score for JSN in all 12 feet joints was 48. Thus, the maximum possible total JSN score for Hands and feet was 168.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
From Baseline (Week 0) in RA0055 Period 1 to Week 104 in RA0055 Period 2
|
||||||||||||||||||||
|
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Change from Week 52 in previous study RA0055 Period 1 in the joint narrowing score to Week 104 in RA0055 Period 2 | ||||||||||||||||||||
End point description |
Joint space narrowing (JSN) was assessed in 15 locations per hand and 6 locations per foot. Joint space narrowing for each location was scored from 0 to 4, with 0 indicating no narrowing. The maximum possible score for JSN in all 30 hand joints was 120. The maximum possible score for JSN in all 12 feet joints was 48. Thus, the maximum possible total JSN score for Hands and feet was 168.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
From Week 52 in RA0055 Period 1 to Week 104 in RA0055 Period 2
|
||||||||||||||||||||
|
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Percentage of subjects meeting the American College of Rheumatology 20 % response criteria (ACR20) at Week 104 in RA0055 Period 2 | ||||||||||||||||||||
End point description |
The assessments are based on a 20 % or greater improvement from Baseline in previous study RA0055 Period 1 in the number of tender joints, a 20 % or more improvement in the number of swollen joints, and a 20 % or greater improvement in 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP).
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
From Baseline (Week 0) in RA0055 Period 1 to Week 104 in RA0055 Period 2
|
||||||||||||||||||||
|
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Percentage of subjects meeting the American College of Rheumatology 50 % response criteria (ACR50) at Week 104 in RA0055 Period 2 | ||||||||||||||||||||
End point description |
The assessments are based on a 50 % or greater improvement from Baseline in previous study RA0055 Period 1 in the number of tender joints, a 50 % or more improvement in the number of swollen joints, and a 50 % or greater improvement in 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP).
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
From Baseline (Week 0) in RA0055 Period 1 to Week 104 in RA0055 Period 2
|
||||||||||||||||||||
|
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Percentage of subjects meeting the American College of Rheumatology 70 % response criteria (ACR70) at Week 104 in RA0055 Period 2 | ||||||||||||||||||||
End point description |
The assessments are based on a 70 % or greater improvement from Baseline in previous study RA0055 Period 1 in the number of tender joints, a 70 % or more improvement in the number of swollen joints, and a 70 % or greater improvement in 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP).
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
From Baseline (Week 0) in RA0055 Period 1 to Week 104 in RA0055 Period 2
|
||||||||||||||||||||
|
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Percentage of subjects meeting the 2011 American College of Rheumatology/ European League Against Rheumatism (ACR/EULAR) remission criteria at Week 104 in RA0055 Period 2 | ||||||||||||||||||||
End point description |
The ACR/EULAR 2011 remission criteria is defined as:
Tender Joint Count (TJC) <= 1, Swollen Joint Count (SJC) <= 1, C-Reactive Protein (CRP) <= 1 mg/dl and Patient's Global Assessment of Disease Activity (PtGADA) <= 10 mm.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
Week 104 in RA0055 Period 2
|
||||||||||||||||||||
|
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Percentage of subjects with Clinical Disease Activity Index (CDAI) <= 2.8 at Week 104 in RA0055 Period 2 | ||||||||||||||||||||
End point description |
CDAI is calculated as the sum of tender joint count (TJC), swollen joint count (SJC), Patient's Global Assessment of Disease Activity - Visual Analog Scale (PtGADA-VAS in mm), and Physician's Global Assessment of Disease Activity - Visual Analog Scale (PhGADA-VAS in mm). 28 joints are examined where a lower score indicates less disease activity.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
Week 104 in RA0055 Period 2
|
||||||||||||||||||||
|
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Percentage of subjects with Simplified Disease Activity Index (SDAI) <= 3.3 at Week 104 in RA0055 Period 2 | ||||||||||||||||||||
End point description |
SDAI is calculated as the sum of tender joint count (TJC), swollen joint count (SJC), Patient's Global Assessment of Disease Activity - Visual Analog Scale (PtGADA-VAS in mm), Physician's Global Assessment of Disease Activity - Visual Analog Scale (PhGADA-VAS in mm) and C-Reactive Protein (CRP in mg/L). 28 joints are examined where a lower score indicates less disease activity.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
Week 104 in RA0055 Period 2
|
||||||||||||||||||||
|
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Percentage of subjects with Disease Activity Score [Erythrocyte Sedimentation Rate] (DAS28[ESR]) < 2.6 at Week 104 in RA0055 Period 2 | ||||||||||||||||||||
End point description |
DAS28[ESR] is calculated using the Tender Joint Count (TJC), Swollen Joint Count (SJC) Erythrocyte Sedimentation Rate (ESR in mm/hour), and the Patient's Global Assessment of Disease Activity - Visual Analog Scale (PtGADA-VAS in mm) using the following formula: 0.56 x √(TJC) + 0.28 x √(SJC) + 0.70 x lognat (ESR) + 0.014 x PtGADA, where 28 joints are examined and a lower score indicates less disease activity.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
Week 104 in RA0055 Period 2
|
||||||||||||||||||||
|
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Percentage of subjects meeting the 2011 American College of Rheumatology/ European League Against Rheumatism (ACR/EULAR) remission criteria simplified for clinical practice at Week 104 in RA0055 Period 2 | ||||||||||||||||||||
End point description |
The 2011 ACR/EULAR remission criteria simplified for clinical practice is defined as:
Tender Joint Count (TJC) <= 1, Swollen Joint Count (SJC) <= 1 and Patient's Global Assessment of Disease Activity (PtGADA) <= 10 mm.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
Week 104 in RA0055 Period 2
|
||||||||||||||||||||
|
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Percentage of subjects achieving a good or moderate European League Against Rheumatism (EULAR) response at Week 104 in RA0055 Period 2 | ||||||||||||||||||||
End point description |
Good response is defined as:
DAS28[ESR] <= 3.2 and decrease from Baseline by >1.2;
moderate response is defined as achievement of one of the following:
- DAS28[ESR] <= 3.2 and decrease from Baseline > 0.6 and ≤ 1.2
- DAS28[ESR] > 3.2 and ≤ 5.1 and decrease from Baseline > 0.6
- DAS28[ESR] > 5.1 and decrease from Baseline >1.2.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
From Baseline (Week 0) in RA0055 Period 1 to Week 104 in RA0055 Period 2
|
||||||||||||||||||||
|
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Change from Baseline in previous study RA0055 Period 1 in Disease Activity Score [Erythrocyte Sedimentation Rate] (DAS28 [ESR]) to Week 104 in RA0055 Period 2 | ||||||||||||||||||||
End point description |
DAS28[ESR] is calculated using the Tender Joint Count (TJC), Swollen Joint Count (SJC) Erythrocyte Sedimentation Rate (ESR in mm/hour), and the Patient's Global Assessment of Disease Activity - Visual Analog Scale (PtGADA-VAS in mm) using the following formula: 0.56 x √(TJC) + 0.28 x √(SJC) + 0.70 x lognat (ESR) + 0.014 x PtGADA, where 28 joints are examined and a lower score indicates less disease activity.
A negative value in DAS28[ESR] change from Baseline indicates an improvement from Baseline.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
From Baseline (Week 0) in RA0055 Period 1 to Week 104 in RA0055 Period 2
|
||||||||||||||||||||
|
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Change from Week 52 in previous study RA0055 Period 1 in Disease Activity Score [Erythrocyte Sedimentation Rate] (DAS28 [ESR]) to Week 104 in RA0055 Period 2 | ||||||||||||||||||||
End point description |
DAS28[ESR] is calculated using the Tender Joint Count (TJC), Swollen Joint Count (SJC) Erythrocyte Sedimentation Rate (ESR in mm/hour), and the Patient's Global Assessment of Disease Activity - Visual Analog Scale (PtGADA-VAS in mm) using the following formula: 0.56 x √(TJC) + 0.28 x √(SJC) + 0.70 x lognat (ESR) + 0.014 x PtGADA, where 28 joints are examined and a lower score indicates less disease activity.
A negative value in DAS28[ESR] change from Baseline indicates an improvement from Baseline.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
From Week 52 in RA0055 Period 1 to Week 104 in RA0055 Period 2
|
||||||||||||||||||||
|
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Change from Baseline in previous study RA0055 Period 1 in Clinical Disease Activity Index (CDAI) to Week 104 in RA0055 Period 2 | ||||||||||||||||||||
End point description |
CDAI is calculated as the sum of tender joint count (TJC), swollen joint count (SJC), Patient's Global Assessment of Disease Activity - Visual Analog Scale (PtGADA-VAS in mm), and Physician's Global Assessment of Disease Activity - Visual Analog Scale (PhGADA-VAS in mm). 28 joints are examined where a lower score indicates less disease activity.
A negative value in CDAI change from Baseline indicates an improvement from Baseline.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
From Baseline (Week 0) in RA0055 Period 1 to Week 104 in RA0055 Period 2
|
||||||||||||||||||||
|
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Change from Week 52 in previous study RA0055 Period 1 in Clinical Disease Activity Index (CDAI) to Week 104 in RA0055 Period 2 | ||||||||||||||||||||
End point description |
CDAI is calculated as the sum of tender joint count (TJC), swollen joint count (SJC), Patient's Global Assessment of Disease Activity - Visual Analog Scale (PtGADA-VAS in mm), and Physician's Global Assessment of Disease Activity - Visual Analog Scale (PhGADA-VAS in mm). 28 joints are examined where a lower score indicates less disease activity.
A negative value in CDAI change from Baseline indicates an improvement from Baseline.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
From Week 52 in RA0055 Period 1 to Week 104 in RA0055 Period 2
|
||||||||||||||||||||
|
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Change from Baseline in previous study RA0055 Period 1 in Simplified Disease Activity Index (SDAI) to Week 104 in RA0055 Period 2 | ||||||||||||||||||||
End point description |
SDAI is calculated as the sum of tender joint count (TJC), swollen joint count (SJC), Patient's Global Assessment of Disease Activity - Visual Analog Scale (PtGADA-VAS in mm), Physician's Global Assessment of Disease Activity - Visual Analog Scale (PhGADA-VAS in mm) and C-Reactive Protein (CRP in mg/L). 28 joints are examined where a lower score indicates less disease activity.
A negative value in SDAI change from Baseline indicates an improvement from Baseline.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
From Baseline (Week 0) in RA0055 Period 1 to Week 104 in RA0055 Period 2
|
||||||||||||||||||||
|
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Change from Week 52 in previous study RA0055 Period 1 in Simplified Disease Activity Index (SDAI) to Week 104 in RA0055 Period 2 | ||||||||||||||||||||
End point description |
SDAI is calculated as the sum of tender joint count (TJC), swollen joint count (SJC), Patient's Global Assessment of Disease Activity - Visual Analog Scale (PtGADA-VAS in mm), Physician's Global Assessment of Disease Activity - Visual Analog Scale (PhGADA-VAS in mm) and C-Reactive Protein (CRP in mg/L). 28 joints are examined where a lower score indicates less disease activity.
A negative value in SDAI change from Baseline indicates an improvement from Baseline.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
From Week 52 in RA0055 Period 1 to Week 104 in RA0055 Period 2
|
||||||||||||||||||||
|
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Percentage of subjects with a Health Assessment Questionnaire- Disability Index (HAQ-DI) ≤ 0.5 at Week 104 in RA0055 Period 2 | ||||||||||||||||||||
End point description |
Normative physical function is defined as HAQ-DI score <= 0.5.
The domains of the HAQ-DI are dressing and grooming, arising, eating, walking, hygiene, reach, grip and common daily activities.
The total score ranges from 0 to 3 with lower scores meaning lower disability.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
Week 104 in RA0055 Period 2
|
||||||||||||||||||||
|
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Percentage of subjects with Disease Activity Score 28 [Erythrocyte Sedimentation Rate] (DAS28 [ESR]) <= 3.2 at Week 104 in RA0055 Period 2 | ||||||||||||||||||||
End point description |
DAS28[ESR] is calculated using the Tender Joint Count (TJC), Swollen Joint Count (SJC) Erythrocyte Sedimentation Rate (ESR in mm/hour), and the Patient's Global Assessment of Disease Activity - Visual Analog Scale (PtGADA-VAS in mm) using the following formula: 0.56 x √(TJC) + 0.28 x √(SJC) + 0.70 x lognat (ESR) + 0.014 x PtGADA, where 28 joints are examined and a lower score indicates less disease activity.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
Week 104 in RA0055 Period 2
|
||||||||||||||||||||
|
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Time to flare from Week 52 in RA0055 Period 1 to Week 104 in RA0055 Period 2 | ||||||||||||||||||||
End point description |
Time to flare, defined as an increase of DAS28[ESR] >= 0.6 above Week 52 DAS28[ESR] level, having a DAS28[ESR] >= 3.2 and judged by the Investigator as due to RA and all three criteria confirmed at an additional visit two weeks thereafter, from Week 52 onwards.
Data not available as > 75% of the participants failed to meet flare criteria.
-999/-9999 = not estimable.
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End point type |
Secondary
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End point timeframe |
Week 104 in RA0055 Period 2
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No statistical analyses for this end point |
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End point title |
Change from Baseline in previous study RA0055 Period 1 in the Bristol Rheumatoid Arthritis Fatigue- Multidimensional Questionnaire (BRAF-MDQ) total score to Week 104 in RA0055 Period 2 | ||||||||||||||||||||
End point description |
BRAF-MDQ total score ranges from 0 to 70 (with higher scores indicating worse fatigue), whereas the score for each dimension is different due to the varied number of questions (0 –22 for physical, 0- 21 for living, 0- 15 for cognition, and 0- 12 for emotion). A negative value in BRAF-MDQ change from Baseline indicates an improvement from Baseline.
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End point type |
Secondary
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End point timeframe |
From Baseline (Week 0) in RA0055 Period 1 to Week 104 in RA0055 Period 2
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No statistical analyses for this end point |
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End point title |
Number of work days missed (Work Productivity Survey - Rheumatoid Arthritis [WPS-RA]) at Week 104 in RA0055 Period 2 | ||||||||||||||||||||
End point description |
Number of work days missed in the last month for employed subjects.
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End point type |
Secondary
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End point timeframe |
Week 104 in RA0055 Period 2
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No statistical analyses for this end point |
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End point title |
Number of work days with reduced productivity (Work Productivity Survey - Rheumatoid Arthritis [WPS-RA]) at Week 104 in RA0055 Period 2 | ||||||||||||||||||||
End point description |
Number of work days with reduced productivity in the last month for employed subjects.
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End point type |
Secondary
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End point timeframe |
Week 104 in RA0055 Period 2
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No statistical analyses for this end point |
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End point title |
Interference with work productivity (Work Productivity Survey - Rheumatoid Arthritis [WPS-RA]) at Week 104 in RA0055 Period 2 | ||||||||||||||||||||
End point description |
The Arthritis interference in the last month with work productivity is measured on a scale that ranges from 0 (no interference) to 10 (complete interference) for employed subjects.
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End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
Week 104 in RA0055 Period 2
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No statistical analyses for this end point |
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End point title |
Number of days with no household work (Work Productivity Survey - Rheumatoid Arthritis [WPS-RA]) at Week 104 in RA0055 Period 2 | ||||||||||||||||||||
End point description |
Number of days with no household work in the last month.
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End point type |
Secondary
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End point timeframe |
Week 104 in RA0055 Period 2
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No statistical analyses for this end point |
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End point title |
Number of days with reduced household work productivity (Work Productivity Survey - Rheumatoid Arthritis [WPS-RA]) at Week 104 in RA0055 Period 2 | ||||||||||||||||||||
End point description |
Number of days with reduced household work productivity in the last month.
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End point type |
Secondary
|
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End point timeframe |
Week 104 in RA0055 Period 2
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No statistical analyses for this end point |
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End point title |
Number of days with hired outside help (Work Productivity Survey - Rheumatoid Arthritis [WPS-RA]) at Week 104 in RA0055 Period 2 | ||||||||||||||||||||
End point description |
Number of days with hired outside help days in the last month.
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End point type |
Secondary
|
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End point timeframe |
Week 104 in RA0055 Period 2
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No statistical analyses for this end point |
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End point title |
Number of days missed of family/social/leisure activities (Work Productivity Survey - Rheumatoid Arthritis [WPS-RA]) at Week 104 in RA0055 Period 2 | ||||||||||||||||||||
End point description |
Number of days missed of family/social/leisure activities in the last month.
|
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End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
Week 104 in RA0055 Period 2
|
||||||||||||||||||||
|
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No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Interference with household work productivity (Work Productivity Survey - Rheumatoid Arthritis [WPS-RA]) at Week 104 in RA0055 Period 2 | ||||||||||||||||||||
End point description |
The Arthritis interference in the last month with household productivity is measured on a scale that ranges from 0 (no interference) to 10 (complete interference).
|
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End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
Week 104 in RA0055 Period 2
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No statistical analyses for this end point |
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End point title |
Percentage of subjects achieving Low Disease Activity (LDA) at Week 104 in RA0055 Period 2 | ||||||||||||||||||||
End point description |
LDA is defined as achieving a Disease Activity Score 28 [Erythrocyte Sedimentation Rate] (DAS28 [ESR]) <= 3.2.
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End point type |
Secondary
|
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End point timeframe |
Week 104 in RA0055 Period 2
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No statistical analyses for this end point |
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Adverse events information
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Timeframe for reporting adverse events |
Adverse events for Period 2 were collected from the date of the Week 52 study medication up to 70 days after the last (most recent) Certolizumab pegol (CZP) or Placebo (PBO) dose
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Adverse event reporting additional description |
For the safety results, the main comparisons of interest are across the 3 CZP re-randomized groups; the PBO+MTX/PBO+MTX group is included for completeness.
For subjects induced/ re-induced with CZP due to flare, only AEs up to the time of induction/re-induction with CZP are included. Note that 3 SAEs occurred after induction/ re-induction.
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Assessment type |
Non-systematic | ||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
17.0
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Reporting groups
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Reporting group title |
PBO+MTX / PBO+MTX
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Reporting group description |
Placebo (PBO) + Methotrexate (MTX) in Period 1 1 syringe PBO every 2 Weeks + MTX in Period 2 | ||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
CZP+MTX / PBO+MTX
|
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Reporting group description |
Certolizumab pegol (CZP) 200 mg Q2W + Methotrexate (MTX) in Period 1 1 syringe PBO every 2 Weeks + MTX in Period 2 | ||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
CZP+MTX / CZP Q4W+MTX
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Reporting group description |
Certolizumab pegol (CZP) 200 mg Q2W + Methotrexate (MTX) in Period 1 1 syringe 200 mg Certolizumab pegol (CZP) every 4 Weeks/ 1 syringe Placebo (PBO) every 4 Weeks (CZP and PBO administration to be staggered 2 weeks apart to maintain blind) + MTX in Period 2 | ||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
CZP+MTX / CZP Q2W+MTX
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Reporting group description |
Certolizumab pegol (CZP) 200 mg Q2W + Methotrexate (MTX) in Period 1 1 syringe 200 mg Certolizumab pegol (CZP) every 2 Weeks + MTX in Period 2 | ||||||||||||||||||||||||||||||||||||||||||
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