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
- Conditions
- Rheumatoid Arthritis
- Interventions
- Registration Number
- NCT01500278
- Lead Sponsor
- UCB Pharma SA
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 915
-
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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Certolizumab Pegol + Methotrexate (CZP + MTX) Certolizumab Pegol (CZP) - Adalimumab + Methotrexate (ADA + MTX) Adalimumab (ADA) - Adalimumab + Methotrexate (ADA + MTX) Methotrexate (MTX) - CZP + MTX followed by ADA + MTX Methotrexate (MTX) Those 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. CZP + MTX followed by ADA + MTX Certolizumab Pegol (CZP) Those 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. CZP + MTX followed by ADA + MTX Adalimumab (ADA) Those 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 Certolizumab Pegol (CZP) Those 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. ADA + MTX followed by CZP + MTX Adalimumab (ADA) Those 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. Certolizumab Pegol + Methotrexate (CZP + MTX) Methotrexate (MTX) - ADA + MTX followed by CZP + MTX Methotrexate (MTX) Those 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.
- Primary Outcome Measures
Name Time Method Percentage of Subjects Who Met the American College of Rheumatology 20 % (ACR20) Criteria at Week 12 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).
Percentage of Subjects Who Had a Disease Activity Score 28 [Erythrocyte Sedimentation Rate] (DAS28 [ESR]) ≤ 3.2 at Week 104 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.
- Secondary Outcome Measures
Name Time Method Percentage of Week 12 Responders Who Had a Disease Activity Score 28 [Erythrocyte Sedimentation Rate] (DAS28 [ESR]) ≤ 3.2 at Week 104 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.
The definition of Week 12 responders was DAS28\[ESR\] Low Disease Activity (LDA) (ie ≤ 3.2) or an improvement of ≥ 1.2 in DAS28\[ESR\] relative to Baseline.Percentage of Subjects Who Met the American College of Rheumatology 20 % (ACR20) Criteria at Week 6 Week 6 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).
Percentage of Subjects Who Had a Disease Activity Score 28 [Erythrocyte Sedimentation Rate] (DAS28 [ESR]) ≤ 3.2 at Week 6 Week 6 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.
Percentage of Subjects Who Had a Disease Activity Score 28 [Erythrocyte Sedimentation Rate] (DAS28 [ESR]) ≤ 3.2 at Week 12 Week 12 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.
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 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.
The definition of Week 6/12 responders was DAS28\[ESR\] Low Disease Activity (LDA) (ie ≤ 3.2) or an improvement of ≥ 1.2 in DAS28\[ESR\] relative to Baseline.Change From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 104 From Baseline to Week 104 HAQ-DI was derived based on the mean of individual scores in 8 categories of daily living actives (using 20 questions). Each question was scored 0-3 (0 = without any difficulty, 1 = with some difficulty, 2 = with much difficulty, and 3 = unable to do), and the total HAQ-DI was scored on the scale of 0-3 as well. Change from Baseline was computed as the value at Week 104 minus the Baseline value. A negative value in Change from Baseline indicates an improvement.
Kaplan-Meier Estimates of Proportion of Subjects Who Discontinued After Response at Week 12 From Week 12 up to Week 104 Response at Week 12 means that a subject had either a Disease Activity Score 28 \[Erythrocyte Sedimentation Rate\] (DAS28 \[ESR\]) ≤ 3.2 at Week 12 or had a reduction of DAS28 \[ESR\] ≥ 1.2 from Baseline to Week 12. Kaplan-Meier Estimates of Proportion of Subjects Discontinued are presented per study week (days relative to Week 12 visit).
Trial Locations
- Locations (175)
166
🇺🇸Houston, Texas, United States
35
🇧🇬Plovdiv, Bulgaria
14
🇵🇹Ponte De Lima, Portugal
4
🇦🇺Hobart, Tasmania, Australia
100
🇭🇺Kistarcsa, Hungary
113
🇵🇱Warszawa, Poland
76
🇵🇹Lisboa, Portugal
96
🇷🇴Galati, Romania
8
🇦🇺Fitzroy, Victoria, Australia
85
🇦🇹Stockerau, Austria
107
🇵🇱Bydgoszcz, Poland
69
🇵🇹Coimbra, Portugal
57
🇷🇴Bucharest, Romania
1
🇦🇺Malvern, Victoria, Australia
18
🇧🇬Pleven, Bulgaria
108
🇵🇱Wroclaw, Poland
159
🇺🇸Tucson, Arizona, United States
144
🇺🇸Menifee, California, United States
161
🇺🇸Fullerton, California, United States
147
🇺🇸Covina, California, United States
142
🇺🇸Aventura, Florida, United States
148
🇺🇸Whittier, California, United States
202
🇺🇸Maywood, Illinois, United States
145
🇺🇸Coeur d'Alene, Idaho, United States
178
🇺🇸Baltimore, Maryland, United States
137
🇺🇸Battle Creek, Michigan, United States
190
🇺🇸Wyomissing, Pennsylvania, United States
155
🇺🇸Lansing, Michigan, United States
170
🇺🇸Reno, Nevada, United States
219
🇺🇸Orchard Park, New York, United States
201
🇺🇸Teaneck, New Jersey, United States
154
🇺🇸Albany, New York, United States
132
🇺🇸Duncansville, Pennsylvania, United States
146
🇺🇸Dallas, Texas, United States
133
🇺🇸Jackson, Tennessee, United States
151
🇺🇸Corpus Christi, Texas, United States
67
🇮🇹Prato, Italy
213
🇺🇸Dallas, Texas, United States
212
🇺🇸Houston, Texas, United States
6
🇦🇺Camperdown, New South Wales, Australia
2
🇦🇺Maroochydore, Queensland, Australia
163
🇺🇸Clarksburg, West Virginia, United States
3
🇦🇺Subiaco, Western Australia, Australia
22
🇦🇹Wien, Austria
21
🇧🇬Sofia, Bulgaria
29
🇧🇬Sofia, Bulgaria
34
🇧🇬Sofia, Bulgaria
70
🇫🇷Le Mans, France
221
🇨🇦Barrie, Canada
171
🇨🇦Quebec, Canada
103
🇨🇿Brno, Czechia
49
🇨🇿Praha, Czechia
61
🇨🇿Hradec Kralove, Czechia
31
🇩🇪Heidelberg, Germany
64
🇩🇪Köln, Germany
37
🇩🇪Herne, Germany
72
🇫🇷Montpellier Cedex 5, France
17
🇩🇪Hamburg, Germany
63
🇩🇪Osnabrück, Germany
68
🇭🇺Gyula, Hungary
33
🇭🇺Veszprem, Hungary
194
🇲🇽Chihuahua, Mexico
106
🇵🇱Poznan, Poland
11
🇩🇪Ratingen, Germany
20
🇮🇪Limerick, Ireland
88
🇮🇹Genova, Italy
13
🇭🇺Budapest, Hungary
51
🇮🇪Dublin, Ireland
195
🇲🇽Chihuahua, Mexico
79
🇮🇹Magenta, Italy
98
🇮🇹Napoli, Italy
80
🇮🇹Bergamo, Italy
38
🇮🇹Genova, Italy
36
🇮🇹Roma, Italy
39
🇮🇹Verona, Italy
193
🇲🇽Guadalajara, Mexico
192
🇲🇽Monterrey, Mexico
191
🇲🇽San Luis Potosi, Mexico
60
🇲🇨Monaco, Monaco
27
🇵🇹Lisbon, Portugal
24
🇷🇴Bucharest, Romania
74
🇷🇴Braila, Romania
25
🇷🇴Bucharest, Romania
52
🇪🇸A Coruna, Spain
73
🇬🇧Upton, United Kingdom
99
🇬🇧Wigan, United Kingdom
30
🇪🇸Madrid, Spain
86
🇬🇧Ashford, United Kingdom
59
🇬🇧Leeds, United Kingdom
77
🇬🇧Poole, United Kingdom
89
🇫🇷Brest, France
62
🇫🇷Lyon, France
172
🇨🇦Hamilton, Ontario, Canada
174
🇨🇦Hamilton, Ontario, Canada
177
🇨🇦Ottawa, Ontario, Canada
40
🇨🇿Uherske Hradiste, Czechia
141
🇺🇸Birmingham, Alabama, United States
140
🇺🇸Cincinnati, Ohio, United States
184
🇺🇸Oklahoma City, Oklahoma, United States
139
🇺🇸San Antonio, Texas, United States
207
🇺🇸Plainview, New York, United States
181
🇺🇸Sugar Land, Texas, United States
217
🇺🇸La Mesa, California, United States
179
🇨🇦Edmonton, Alberta, Canada
214
🇺🇸Tuscaloosa, Alabama, United States
152
🇺🇸Hot Springs, Arkansas, United States
149
🇺🇸Los Angeles, California, United States
189
🇺🇸Van Nuys, California, United States
220
🇺🇸Lewes, Delaware, United States
216
🇺🇸Fort Lauderdale, Florida, United States
153
🇺🇸Detroit, Michigan, United States
209
🇺🇸Vero Beach, Florida, United States
204
🇺🇸Eagan, Minnesota, United States
143
🇺🇸Saint Louis Park, Minnesota, United States
180
🇺🇸Rochester, Minnesota, United States
135
🇺🇸Omaha, Nebraska, United States
150
🇺🇸Voorhees, New Jersey, United States
167
🇺🇸Syracuse, New York, United States
136
🇺🇸Brooklyn, New York, United States
187
🇺🇸Myrtle Beach, South Carolina, United States
164
🇺🇸Bethlehem, Pennsylvania, United States
160
🇺🇸Knoxville, Tennessee, United States
131
🇺🇸Dallas, Texas, United States
203
🇺🇸Orangeburg, South Carolina, United States
211
🇺🇸Arlington, Virginia, United States
215
🇺🇸Glendale, Wisconsin, United States
218
🇨🇦Rimouski, Quebec, Canada
46
🇧🇬Sofia, Bulgaria
183
🇨🇦Halifax, Nova Scotia, Canada
206
🇨🇦Ottawa, Ontario, Canada
175
🇨🇦St. Catharines, Ontario, Canada
169
🇨🇦Sainte Foy, Quebec, Canada
58
🇨🇿Plzen, Czechia
90
🇫🇷Orleans, France
43
🇭🇺Szeged, Hungary
95
🇬🇷Larisa, Greece
56
🇩🇪Berlin, Germany
105
🇫🇷Toulouse Cedex 9, France
47
🇩🇪Fulda, Germany
71
🇩🇪Traunstein, Germany
66
🇩🇪Rheine, Germany
94
🇬🇷Heraklion, Greece
44
🇩🇪Zerbst, Germany
48
🇩🇪Rostock, Germany
42
🇭🇺Budapest, Hungary
23
🇮🇪Dublin, Ireland
115
🇵🇱Warszawa, Poland
81
🇵🇹Porto, Portugal
54
🇷🇴Bacau, Romania
12
🇷🇴Cluj-Napoca, Romania
28
🇷🇴Bucharest, Romania
32
🇷🇴Bucharest, Romania
26
🇷🇴Iasi, Romania
65
🇪🇸Vigo, Spain
16
🇪🇸A Coruna, Spain
83
🇪🇸Madrid, Spain
82
🇪🇸Sabadell, Spain
53
🇨🇭St. Gallen, Switzerland
50
🇨🇭Zürich, Switzerland
78
🇬🇧Brighton, United Kingdom
55
🇬🇧Sheffield, United Kingdom
19
🇬🇧London, United Kingdom
208
🇺🇸Sacramento, California, United States
185
🇺🇸Roseville, California, United States
157
🇺🇸Spokane, Washington, United States
5
🇦🇺Kogarah, New South Wales, Australia
162
🇺🇸Gainesville, Florida, United States
134
🇺🇸Lexington, Kentucky, United States
205
🇺🇸Albuquerque, New Mexico, United States
210
🇺🇸Charleston, South Carolina, United States
138
🇺🇸Austin, Texas, United States
7
🇦🇺Clayton, Victoria, Australia
176
🇨🇦St. John's, Newfoundland and Labrador, Canada
165
🇺🇸Victoria, Texas, United States
168
🇨🇦St. John's, Newfoundland and Labrador, Canada