Rheumatoid ArthritisPhase 4NCT01500278
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 Phase 4 study testing Certolizumab Pegol (CZP), Adalimumab (ADA) and Methotrexate (MTX) in people with Rheumatoid Arthritis, run by UCB Pharma SA at 175 sites in 20 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Rheumatoid Arthritis
- What is being tested?
- Certolizumab Pegol (CZP), Adalimumab (ADA) and Methotrexate (MTX)
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 915 participants
- Where
- 175 sitesin 20 countries
- Study dates
- Dec 2011to Jan 2016
- Phase
- Phase 4
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 12Show fewer
- 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
Who cannot join
- 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
Trial locations and contacts
175 sites in 20 countries.
175 sites in 20 countries
United States62 sites
154
Albany, New York
205
Albuquerque, New Mexico
211
Arlington, Virginia
138
Austin, Texas
142
Aventura, Florida
178
Baltimore, Maryland
137
Battle Creek, Michigan
164
Bethlehem, Pennsylvania
141
Birmingham, Alabama
136
Brooklyn, New York
210
Charleston, South Carolina
140
Cincinnati, Ohio
163
Clarksburg, West Virginia
145
Coeur d'Alene, Idaho
151
Corpus Christi, Texas
147
Covina, California
131
Dallas, Texas
146
Dallas, Texas
213
Dallas, Texas
153
Detroit, Michigan
132
Duncansville, Pennsylvania
204
Eagan, Minnesota
216
Fort Lauderdale, Florida
161
Fullerton, California
162
Gainesville, Florida
215
Glendale, Wisconsin
152
Hot Springs, Arkansas
166
Houston, Texas
212
Houston, Texas
133
Jackson, Tennessee
160
Knoxville, Tennessee
217
La Mesa, California
155
Lansing, Michigan
220
Lewes, Delaware
134
Lexington, Kentucky
149
Los Angeles, California
202
Maywood, Illinois
144
Menifee, California
187
Myrtle Beach, South Carolina
184
Oklahoma City, Oklahoma
135
Omaha, Nebraska
203
Orangeburg, South Carolina
219
Orchard Park, New York
207
Plainview, New York
170
Reno, Nevada
180
Rochester, Minnesota
185
Roseville, California
208
Sacramento, California
143
Saint Louis Park, Minnesota
139
San Antonio, Texas
157
Spokane, Washington
181
Sugar Land, Texas
167
Syracuse, New York
201
Teaneck, New Jersey
159
Tucson, Arizona
214
Tuscaloosa, Alabama
189
Van Nuys, California
209
Vero Beach, Florida
165
Victoria, Texas
150
Voorhees Township, New Jersey
148
Whittier, California
190
Wyomissing, Pennsylvania
Canada13 sites
221
Barrie
179
Edmonton, Alberta
183
Halifax, Nova Scotia
172
Hamilton, Ontario
174
Hamilton, Ontario
177
Ottawa, Ontario
206
Ottawa, Ontario
171
Québec
218
Rimouski, Quebec
169
Sainte-Foy, Quebec
175
St. Catharines, Ontario
168
St. John's, Newfoundland and Labrador
176
St. John's, Newfoundland and Labrador
Germany12 sites
56
Berlin
64
Cologne
47
Fulda
17
Hamburg
31
Heidelberg
37
Herne
63
Osnabrück
11
Ratingen
66
Rheine
48
Rostock
71
Traunstein
44
Zerbst
Romania10 sites
54
Bacau
74
Brăila
24
Bucharest
25
Bucharest
28
Bucharest
32
Bucharest
57
Bucharest
12
Cluj-Napoca
96
Galati
26
Iași
Australia8 sites
6
Camperdown, New South Wales
7
Clayton, Victoria
8
Fitzroy, Victoria
4
Hobart, Tasmania
5
Kogarah, New South Wales
1
Malvern, Victoria
2
Maroochydore, Queensland
3
Subiaco, Western Australia
Italy8 sites
80
Bergamo
38
Genova
88
Genova
79
Magenta
98
Naples
67
Prato
36
Roma
39
Verona
United Kingdom8 sites
86
Ashford
78
Brighton
59
Leeds
19
London
77
Poole
55
Sheffield
73
Upton
99
Wigan
Hungary6 sites
13
Budapest
42
Budapest
68
Gyula
100
Kistarcsa
43
Szeged
33
Veszprém
Mexico5 sites
194
Chihuahua City
195
Chihuahua City
193
Guadalajara
192
Monterrey
191
San Luis Potosí City
About this study
Official title: 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
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.
- Conditions
- Rheumatoid Arthritis
- Being tested
- Certolizumab Pegol (CZP), Adalimumab (ADA), Methotrexate (MTX)
- Keywords
- Certolizumab Pegol, Cimzia, Adalimumab, Humira, Rheumatoid Arthritis
- Medical subject headings
- Arthritis, Rheumatoid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Certolizumab Pegol (CZP)Biological
Also called Cimzia, CZP
- 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.
Adalimumab (ADA)Biological
Also called Humira, ADA
- 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.
Methotrexate (MTX)Drug
Also called MTX
- Active substance: Methotrexate
- Pharmaceutical form: oral tablet
- Concentration: 15-25 mg/week
- Route of Administration: MTX orally
| Study group | Role | What they receive |
|---|---|---|
| Certolizumab Pegol + Methotrexate (CZP + MTX) | Active comparator | Not described Receives: Biological: Certolizumab Pegol (CZP); Drug: Methotrexate (MTX) |
| Adalimumab + Methotrexate (ADA + MTX) | Active comparator | Not described Receives: Biological: Adalimumab (ADA); Drug: Methotrexate (MTX) |
| CZP + MTX followed by ADA + MTX | Active comparator | 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. Receives: Biological: Certolizumab Pegol (CZP); Biological: Adalimumab (ADA); Drug: Methotrexate (MTX) |
| ADA + MTX followed by CZP + MTX | Active comparator | 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. Receives: Biological: Certolizumab Pegol (CZP); Biological: Adalimumab (ADA); Drug: Methotrexate (MTX) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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.
Measured: 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
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.
Measured: Week 104
Percentage of Subjects Who Met the American College of Rheumatology 20 % (ACR20) Criteria at 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).
Measured: Week 6
Percentage of Subjects Who Had a Disease Activity Score 28 [Erythrocyte Sedimentation Rate] (DAS28 [ESR]) ≤ 3.2 at 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.
Measured: Week 6
Percentage of Subjects Who Had a Disease Activity Score 28 [Erythrocyte Sedimentation Rate] (DAS28 [ESR]) ≤ 3.2 at 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.
Measured: 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
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.
Measured: Week 104
Change From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) at 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.
Measured: From Baseline to Week 104
Kaplan-Meier Estimates of Proportion of Subjects Who Discontinued After Response at Week 12
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).
Measured: From Week 12 up to Week 104
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Dec 2011 (estimated)
- Study startDec 2011
- Primary completionNov 2015
- Study completionJan 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Rheumatoid ArthritisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 915 participants (actual)
Sponsor and investigators
- Lead sponsor
- UCB Pharma SA
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Parexel
- Responsible party
- Sponsor
- Investigators
- UCB Cares, Study director, +1 877 822 9493 (UCB)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01500278
- Sponsor's protocol ID
- RA0077
- Other IDs
- 2011-002067-20
- Status last verified
- Jul 2017
- First submitted
- 22 Dec 2011
- Last updated
- 31 Jul 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Expanded access
- Available
Publications
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.
PubMed 27863807Smolen 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.
PubMed 39222436Paul 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.
PubMed 32100960