Study to Assess the Short- and Long-term Efficacy of Certolizumab Pegol Plus Methotrexate Compared to Adalimumab Plus Methotrexate in Subjects With Moderate to Severe Rheumatoid Arthritis (RA) Inadequately Responding to Methotrexate
A Multicenter, Single-blind, Randomized Parallel-group Study to Assess the Short- and Long-term Efficacy of Certolizumab Pegol Plus Methotrexate Compared to Adalimumab Plus Methotrexate in Subjects With Moderate to Severe Rheumatoid Arthritis Responding Inadequately to Methotrexate
2 other identifiers
interventional
915
19 countries
167
Brief Summary
This study is conducted to evaluate the short (12 Weeks) and long term (104 Weeks) efficacy of Certolizumab Pegol compared with Adalimumab both in combination with Methotrexate (MTX) in the treatment of moderate to severe Rheumatoid Arthritis (RA) that is not responding adequately to MTX.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_4 rheumatoid-arthritis
Started Dec 2011
Typical duration for phase_4 rheumatoid-arthritis
167 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
December 1, 2011
CompletedFirst Submitted
Initial submission to the registry
December 22, 2011
CompletedFirst Posted
Study publicly available on registry
December 28, 2011
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 1, 2015
CompletedStudy Completion
Last participant's last visit for all outcomes
January 1, 2016
CompletedResults Posted
Study results publicly available
March 31, 2017
CompletedJuly 31, 2018
July 1, 2017
3.9 years
December 22, 2011
November 22, 2016
July 4, 2018
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Percentage of Subjects Who Met the American College of Rheumatology 20 % (ACR20) Criteria at Week 12
Subjects who met the ACR20 criteria were those subjects with at least 20% improvement from Baseline for Tender Joint Count (TJC), Swollen Joint Count (SJC), and at least 3 of the 5 remaining core set measures: 1) Health Assessment Questionnaire-Disability Index (HAQ-DI), 2) C-reactive Protein (CRP), 3) Patient's Assessment of Arthritis Pain-Visual Analog Scale (PAAP-VAS), 4) Patient's Global Assessment of Disease Activity-Visual Analog Scale (PtGADA-VAS), 5) Physician's Global Assessment of Disease Activity-Visual Analog Scale (PhGA-VAS).
Week 12
Percentage of Subjects Who Had a Disease Activity Score 28 [Erythrocyte Sedimentation Rate] (DAS28 [ESR]) ≤ 3.2 at Week 104
DAS28 \[ESR\] was 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 Patient Global Assessment of Arthritis, where 28 joints were examined and a lower score indicates less disease activity.
Week 104
Secondary Outcomes (7)
Percentage of Week 12 Responders Who Had a Disease Activity Score 28 [Erythrocyte Sedimentation Rate] (DAS28 [ESR]) ≤ 3.2 at Week 104
Week 104
Percentage of Subjects Who Met the American College of Rheumatology 20 % (ACR20) Criteria at Week 6
Week 6
Percentage of Subjects Who Had a Disease Activity Score 28 [Erythrocyte Sedimentation Rate] (DAS28 [ESR]) ≤ 3.2 at Week 6
Week 6
Percentage of Subjects Who Had a Disease Activity Score 28 [Erythrocyte Sedimentation Rate] (DAS28 [ESR]) ≤ 3.2 at Week 12
Week 12
Percentage of Subjects With a Disease Activity Score 28 [Erythrocyte Sedimentation Rate] (DAS28 [ESR]) ≤ 3.2 at Week 104, in Subjects Responding at Both Week 6 and Week 12
Week 104
- +2 more secondary outcomes
Study Arms (4)
Certolizumab Pegol + Methotrexate (CZP + MTX)
ACTIVE COMPARATORAdalimumab + Methotrexate (ADA + MTX)
ACTIVE COMPARATORCZP + MTX followed by ADA + MTX
ACTIVE COMPARATORThose subjects who received Certolizumab Pegol (400 mg at Weeks 0, 2, 4 followed by 200 mg every two weeks) + Methotrexate (CZP+ MTX) at Baseline and are Non-Responders at Week 12, switch to Adalimumab (40 mg) + Methotrexate (ADA + MTX) after Week 12.
ADA + MTX followed by CZP + MTX
ACTIVE COMPARATORThose subjects who received Adalimumab (40 mg + Placebo at Weeks 0, 2, 4 followed by 40 mg ADA every two weeks) + Methotrexate (ADA+ MTX) at Baseline and are Non-Responders at Week 12, switch to Certolizumab Pegol (400 mg at Weeks 12, 14, 16 followed by 200 mg every two weeks) + Methotrexate (CZP+ MTX) after Week 12.
Interventions
* Active substance: an injectable volume of 1 ml solution for injection CZP * Pharmaceutical form: prefilled syringes CZP * Concentration: 200 mg/ml CZP * Route of Administration: injections will be given subcutaneously: loading dose of CZP 400 mg at Baseline, and Weeks 2 and 4, followed by a maintenance dose of 200 mg every 2 weeks through Week 102 or withdrawal.
* Active substance: an injectable volume of 0.8 ml solution for injection ADA * Pharmaceutical form: prefilled syringes ADA * Concentration: 40 mg/0.8 ml ADA * Route of Administration: injections will be given subcutaneously. ADA 40 mg plus an injection with Placebo (to preserve blind) at Baseline, and Weeks 2 and 4, followed by ADA 40 mg every 2 weeks through Week 102 or withdrawal.
* Active substance: Methotrexate * Pharmaceutical form: oral tablet * Concentration: 15-25 mg/week * Route of Administration: MTX orally
Eligibility Criteria
You may qualify if:
- Subject must have a diagnosis of Rheumatoid Arthritis (RA) at Screening, as defined by the 2010 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) classification criteria (Aletaha D et al, 2010)
- Subject must have a positive Rheumatoid Factor (RF) and/or a positive anti-Cyclic Citrullinated Peptide antibody (anti-CCP) as determined by the central laboratory at Screening
- Subject must have moderate to severe RA disease at Screening and Baseline defined as:
- Screening (all criteria required)
- ≥ 4 swollen joints (of 28 prespecified joints)
- Disease Activity Score \[Erythrocyte Sedimentation Rate\] (DAS28\[ESR\]) \> 3.2
- C-Reactive Protein (CRP) concentration ≥ 10 mg/L (or 1.0 mg/dL) or Erythrocyte Sedimentation Rate (ESR) (Westergren) ≥ 28 mm/hr
- Baseline (both criteria required)
- ≥ 4 swollen joints (of 28 prespecified joints)
- Disease Activity Score \[Erythrocyte Sedimentation Rate\] (DAS28\[ESR\]) \> 3.2
- Subject must have inadequately responded previously to Methotrexate (MTX)
- Subject is using MTX 15 to 25 mg/week orally or subcutaneously at Screening and has used the same MTX regimen for a minimum of 28 days prior to Baseline
You may not qualify if:
- Subject has previously received any biological Disease Modifying Antirheumatic Drug (DMARD) or has received treatment with cyclophosphamide, chlorambucil, Janus Kinase, phosphodiesterase 4 inhibitors or investigational agents such as spleen tyrosine kinase
- Diagnosis of any other inflammatory arthritis
- Infected with Tuberculosis (TB) or high risk of acquiring TB infection
- Subjects with concurrent acute or chronic viral hepatitis B or C infection
- Subjects with a history of chronic or recurrent infections or subjects at high risk of infection
- Use of prohibited medications like nonbiological DMARDs (excluding MTX), biological DMARDs excluding study medications, experimental therapy, IA hyaluronic acid
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- UCB Pharma SAlead
- Parexelcollaborator
Study Sites (175)
141
Birmingham, Alabama, United States
214
Tuscaloosa, Alabama, United States
159
Tucson, Arizona, United States
152
Hot Springs, Arkansas, United States
147
Covina, California, United States
161
Fullerton, California, United States
217
La Mesa, California, United States
149
Los Angeles, California, United States
144
Menifee, California, United States
185
Roseville, California, United States
208
Sacramento, California, United States
189
Van Nuys, California, United States
148
Whittier, California, United States
220
Lewes, Delaware, United States
142
Aventura, Florida, United States
216
Fort Lauderdale, Florida, United States
162
Gainesville, Florida, United States
209
Vero Beach, Florida, United States
145
Coeur d'Alene, Idaho, United States
202
Maywood, Illinois, United States
134
Lexington, Kentucky, United States
178
Baltimore, Maryland, United States
137
Battle Creek, Michigan, United States
153
Detroit, Michigan, United States
155
Lansing, Michigan, United States
204
Eagan, Minnesota, United States
180
Rochester, Minnesota, United States
143
Saint Louis Park, Minnesota, United States
135
Omaha, Nebraska, United States
170
Reno, Nevada, United States
201
Teaneck, New Jersey, United States
150
Voorhees Township, New Jersey, United States
205
Albuquerque, New Mexico, United States
154
Albany, New York, United States
136
Brooklyn, New York, United States
219
Orchard Park, New York, United States
207
Plainview, New York, United States
167
Syracuse, New York, United States
140
Cincinnati, Ohio, United States
184
Oklahoma City, Oklahoma, United States
164
Bethlehem, Pennsylvania, United States
132
Duncansville, Pennsylvania, United States
190
Wyomissing, Pennsylvania, United States
210
Charleston, South Carolina, United States
187
Myrtle Beach, South Carolina, United States
203
Orangeburg, South Carolina, United States
133
Jackson, Tennessee, United States
160
Knoxville, Tennessee, United States
138
Austin, Texas, United States
151
Corpus Christi, Texas, United States
131
Dallas, Texas, United States
146
Dallas, Texas, United States
213
Dallas, Texas, United States
166
Houston, Texas, United States
212
Houston, Texas, United States
139
San Antonio, Texas, United States
181
Sugar Land, Texas, United States
165
Victoria, Texas, United States
211
Arlington, Virginia, United States
157
Spokane, Washington, United States
163
Clarksburg, West Virginia, United States
215
Glendale, Wisconsin, United States
6
Camperdown, New South Wales, Australia
5
Kogarah, New South Wales, Australia
2
Maroochydore, Queensland, Australia
4
Hobart, Tasmania, Australia
7
Clayton, Victoria, Australia
8
Fitzroy, Victoria, Australia
1
Malvern, Victoria, Australia
3
Subiaco, Western Australia, Australia
85
Stockerau, Austria
22
Vienna, Austria
18
Pleven, Bulgaria
35
Plovdiv, Bulgaria
21
Sofia, Bulgaria
29
Sofia, Bulgaria
34
Sofia, Bulgaria
46
Sofia, Bulgaria
179
Edmonton, Alberta, Canada
168
St. John's, Newfoundland and Labrador, Canada
176
St. John's, Newfoundland and Labrador, Canada
183
Halifax, Nova Scotia, Canada
172
Hamilton, Ontario, Canada
174
Hamilton, Ontario, Canada
177
Ottawa, Ontario, Canada
206
Ottawa, Ontario, Canada
175
St. Catharines, Ontario, Canada
218
Rimouski, Quebec, Canada
169
Sainte-Foy, Quebec, Canada
221
Barrie, Canada
171
Québec, Canada
103
Brno, Czechia
61
Hradec Králové, Czechia
58
Pilsen, Czechia
49
Prague, Czechia
40
Uherské Hradiště, Czechia
89
Brest, France
70
Le Mans, France
62
Lyon, France
72
Montpellier, France
90
Orléans, France
105
Toulouse, France
56
Berlin, Germany
64
Cologne, Germany
47
Fulda, Germany
17
Hamburg, Germany
31
Heidelberg, Germany
37
Herne, Germany
63
Osnabrück, Germany
11
Ratingen, Germany
66
Rheine, Germany
48
Rostock, Germany
71
Traunstein, Germany
44
Zerbst, Germany
94
Heraklion, Greece
95
Larissa, Greece
13
Budapest, Hungary
42
Budapest, Hungary
68
Gyula, Hungary
100
Kistarcsa, Hungary
43
Szeged, Hungary
33
Veszprém, Hungary
23
Dublin, Ireland
51
Dublin, Ireland
20
Limerick, Ireland
80
Bergamo, Italy
38
Genova, Italy
88
Genova, Italy
79
Magenta, Italy
98
Napoli, Italy
67
Prato, Italy
36
Roma, Italy
39
Verona, Italy
194
Chihuahua City, Mexico
195
Chihuahua City, Mexico
193
Guadalajara, Mexico
192
Monterrey, Mexico
191
San Luis Potosí City, Mexico
60
Monaco, Monaco
107
Bydgoszcz, Poland
106
Poznan, Poland
113
Warsaw, Poland
115
Warsaw, Poland
108
Wroclaw, Poland
69
Coimbra, Portugal
27
Lisbon, Portugal
76
Lisbon, Portugal
14
Ponte de Lima, Portugal
81
Porto, Portugal
54
Bacau, Romania
74
Brăila, Romania
24
Bucharest, Romania
25
Bucharest, Romania
28
Bucharest, Romania
32
Bucharest, Romania
57
Bucharest, Romania
12
Cluj-Napoca, Romania
96
Galati, Romania
26
Iași, Romania
16
A Coruña, Spain
52
A Coruña, Spain
30
Madrid, Spain
83
Madrid, Spain
82
Sabadell, Spain
65
Vigo, Spain
53
Sankt Gallen, Switzerland
50
Zurich, Switzerland
86
Ashford, United Kingdom
78
Brighton, United Kingdom
59
Leeds, United Kingdom
19
London, United Kingdom
77
Poole, United Kingdom
55
Sheffield, United Kingdom
73
Upton, United Kingdom
99
Wigan, United Kingdom
Related Publications (3)
Smolen JS, Burmester GR, Combe B, Curtis JR, Hall S, Haraoui B, van Vollenhoven R, Cioffi C, Ecoffet C, Gervitz L, Ionescu L, Peterson L, Fleischmann R. Head-to-head comparison of certolizumab pegol versus adalimumab in rheumatoid arthritis: 2-year efficacy and safety results from the randomised EXXELERATE study. Lancet. 2016 Dec 3;388(10061):2763-2774. doi: 10.1016/S0140-6736(16)31651-8. Epub 2016 Nov 15.
PMID: 27863807RESULTSmolen JS, Taylor PC, Tanaka Y, Takeuchi T, Hashimoto M, Cara C, Lauwerys B, Tilt N, Ufuktepe B, Xavier RM, Balsa A, Curtis JR, Mikuls TR, Weinblatt M. Impact of high rheumatoid factor levels on treatment outcomes with certolizumab pegol and adalimumab in patients with rheumatoid arthritis. Rheumatology (Oxford). 2024 Nov 1;63(11):3015-3024. doi: 10.1093/rheumatology/keae435.
PMID: 39222436DERIVEDPaul S, Marotte H, Kavanaugh A, Goupille P, Kvien TK, de Longueville M, Mulleman D, Sandborn WJ, Vande Casteele N. Exposure-Response Relationship of Certolizumab Pegol and Achievement of Low Disease Activity and Remission in Patients With Rheumatoid Arthritis. Clin Transl Sci. 2020 Jul;13(4):743-751. doi: 10.1111/cts.12760. Epub 2020 Apr 1.
PMID: 32100960DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- UCB
- Organization
- Cares
Study Officials
- STUDY DIRECTOR
UCB Cares
+1 877 822 9493 (UCB)
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- GT60
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 4
- Allocation
- RANDOMIZED
- Masking
- SINGLE
- Who Masked
- OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
- Expanded Access
- Yes
Study Record Dates
First Submitted
December 22, 2011
First Posted
December 28, 2011
Study Start
December 1, 2011
Primary Completion
November 1, 2015
Study Completion
January 1, 2016
Last Updated
July 31, 2018
Results First Posted
March 31, 2017
Record last verified: 2017-07