Clinical trial NCT01500278: 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Rheumatoid Arthritis
Keywords: Certolizumab Pegol
Cimzia
Adalimumab
Humira
Rheumatoid Arthritis
Lead sponsor: UCB Pharma
Sponsor class: INDUSTRY
Collaborators: name: Parexel
First posted: 2011-12-28
Enrollment: 915
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* 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:

  1. 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
  2. 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Percentage of Subjects Who Met the American College of Rheumatology 20 % (ACR20) Criteria at Week 12
timeFrame: Week 12
measure: Percentage of Subjects Who Had a Disease Activity Score 28 [Erythrocyte Sedimentation Rate] (DAS28 [ESR]) ≤ 3.2 at Week 104
timeFrame: Week 104
Secondary outcomes:
measure: Percentage of Week 12 Responders Who Had a Disease Activity Score 28 [Erythrocyte Sedimentation Rate] (DAS28 [ESR]) ≤ 3.2 at Week 104
timeFrame: Week 104
measure: Percentage of Subjects Who Met the American College of Rheumatology 20 % (ACR20) Criteria at Week 6
timeFrame: Week 6
measure: Percentage of Subjects Who Had a Disease Activity Score 28 [Erythrocyte Sedimentation Rate] (DAS28 [ESR]) ≤ 3.2 at Week 6
timeFrame: Week 6
measure: Percentage of Subjects Who Had a Disease Activity Score 28 [Erythrocyte Sedimentation Rate] (DAS28 [ESR]) ≤ 3.2 at Week 12
timeFrame: Week 12
measure: 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
timeFrame: Week 104
measure: Change From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 104
timeFrame: From Baseline to Week 104
measure: Kaplan-Meier Estimates of Proportion of Subjects Who Discontinued After Response at Week 12
timeFrame: From Week 12 up to Week 104
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: 141
state: Alabama
city: Tuscaloosa
country: United States
facility: 214
state: Alabama
city: Tucson
country: United States
facility: 159
state: Arizona
city: Hot Springs
country: United States
facility: 152
state: Arkansas
city: Covina
country: United States
facility: 147
state: California
city: Fullerton
country: United States
facility: 161
state: California
city: La Mesa
country: United States
facility: 217
state: California
city: Los Angeles
country: United States
facility: 149
state: California
city: Menifee
country: United States
facility: 144
state: California
city: Roseville
country: United States
facility: 185
state: California
city: Sacramento
country: United States
facility: 208
state: California
city: Van Nuys
country: United States
facility: 189
state: California
city: Whittier
country: United States
facility: 148
state: California
city: Lewes
country: United States
facility: 220
state: Delaware
city: Aventura
country: United States
facility: 142
state: Florida
city: Fort Lauderdale
country: United States
facility: 216
state: Florida
city: Gainesville
country: United States
facility: 162
state: Florida
city: Vero Beach
country: United States
facility: 209
state: Florida
city: Coeur d'Alene
country: United States
facility: 145
state: Idaho
city: Maywood
country: United States
facility: 202
state: Illinois
city: Lexington
country: United States
facility: 134
state: Kentucky
city: Baltimore
country: United States
facility: 178
state: Maryland
city: Battle Creek
country: United States
facility: 137
state: Michigan
city: Detroit
country: United States
facility: 153
state: Michigan
city: Lansing
country: United States
facility: 155
state: Michigan
city: Eagan
country: United States
facility: 204
state: Minnesota
city: Rochester
country: United States
facility: 180
state: Minnesota
city: Saint Louis Park
country: United States
facility: 143
state: Minnesota
city: Omaha
country: United States
facility: 135
state: Nebraska
city: Reno
country: United States
facility: 170
state: Nevada
city: Teaneck
country: United States
facility: 201
state: New Jersey
city: Voorhees
country: United States
facility: 150
state: New Jersey
city: Albuquerque
country: United States
facility: 205
state: New Mexico
city: Albany
country: United States
facility: 154
state: New York
city: Brooklyn
country: United States
facility: 136
state: New York
city: Orchard Park
country: United States
facility: 219
state: New York
city: Plainview
country: United States
facility: 207
state: New York
city: Syracuse
country: United States
facility: 167
state: New York
city: Cincinnati
country: United States
facility: 140
state: Ohio
city: Oklahoma City
country: United States
facility: 184
state: Oklahoma
city: Bethlehem
country: United States
facility: 164
state: Pennsylvania
city: Duncansville
country: United States
facility: 132
state: Pennsylvania
city: Wyomissing
country: United States
facility: 190
state: Pennsylvania
city: Charleston
country: United States
facility: 210
state: South Carolina
city: Myrtle Beach
country: United States
facility: 187
state: South Carolina
city: Orangeburg
country: United States
facility: 203
state: South Carolina
city: Jackson
country: United States
facility: 133
state: Tennessee
city: Knoxville
country: United States
facility: 160
state: Tennessee
city: Austin
country: United States
facility: 138
state: Texas
city: Corpus Christi
country: United States
facility: 151
state: Texas
city: Dallas
country: United States
facility: 131
state: Texas
city: Dallas
country: United States
facility: 146
state: Texas
city: Dallas
country: United States
facility: 213
state: Texas
city: Houston
country: United States
facility: 166
state: Texas
city: Houston
country: United States
facility: 212
state: Texas
city: San Antonio
country: United States
facility: 139
state: Texas
city: Sugar Land
country: United States
facility: 181
state: Texas
city: Victoria
country: United States
facility: 165
state: Texas
city: Arlington
country: United States
facility: 211
state: Virginia
city: Spokane
country: United States
facility: 157
state: Washington
city: Clarksburg
country: United States
facility: 163
state: West Virginia
city: Glendale
country: United States
facility: 215
state: Wisconsin
city: Camperdown
country: Australia
facility: 6
state: New South Wales
city: Kogarah
country: Australia
facility: 5
state: New South Wales
city: Maroochydore
country: Australia
facility: 2
state: Queensland
city: Hobart
country: Australia
facility: 4
state: Tasmania
city: Clayton
country: Australia
facility: 7
state: Victoria
city: Fitzroy
country: Australia
facility: 8
state: Victoria
city: Malvern
country: Australia
facility: 1
state: Victoria
city: Subiaco
country: Australia
facility: 3
state: Western Australia
city: Stockerau
country: Austria
facility: 85
city: Wien
country: Austria
facility: 22
city: Pleven
country: Bulgaria
facility: 18
city: Plovdiv
country: Bulgaria
facility: 35
city: Sofia
country: Bulgaria
facility: 21
city: Sofia
country: Bulgaria
facility: 29
city: Sofia
country: Bulgaria
facility: 34
city: Sofia
country: Bulgaria
facility: 46
city: Edmonton
country: Canada
facility: 179
state: Alberta
city: St. John's
country: Canada
facility: 168
state: Newfoundland and Labrador
city: St. John's
country: Canada
facility: 176
state: Newfoundland and Labrador
city: Halifax
country: Canada
facility: 183
state: Nova Scotia
city: Hamilton
country: Canada
facility: 172
state: Ontario
city: Hamilton
country: Canada
facility: 174
state: Ontario
city: Ottawa
country: Canada
facility: 177
state: Ontario
city: Ottawa
country: Canada
facility: 206
state: Ontario
city: St. Catharines
country: Canada
facility: 175
state: Ontario
city: Rimouski
country: Canada
facility: 218
state: Quebec
city: Sainte Foy
country: Canada
facility: 169
state: Quebec
city: Barrie
country: Canada
facility: 221
city: Quebec
country: Canada
facility: 171
city: Brno
country: Czechia
facility: 103
city: Hradec Kralove
country: Czechia
facility: 61
city: Plzen
country: Czechia
facility: 58
city: Praha
country: Czechia
facility: 49
city: Uherske Hradiste
country: Czechia
facility: 40
city: Brest
country: France
facility: 89
city: Le Mans
country: France
facility: 70
city: Lyon
country: France
facility: 62
city: Montpellier Cedex 5
country: France
facility: 72
city: Orleans
country: France
facility: 90
city: Toulouse Cedex 9
country: France
facility: 105
city: Berlin
country: Germany
facility: 56
city: Fulda
country: Germany
facility: 47
city: Hamburg
country: Germany
facility: 17
city: Heidelberg
country: Germany
facility: 31
city: Herne
country: Germany
facility: 37
city: Köln
country: Germany
facility: 64
city: Osnabrück
country: Germany
facility: 63
city: Ratingen
country: Germany
facility: 11
city: Rheine
country: Germany
facility: 66
city: Rostock
country: Germany
facility: 48
city: Traunstein
country: Germany
facility: 71
city: Zerbst
country: Germany
facility: 44
city: Heraklion
country: Greece
facility: 94
city: Larisa
country: Greece
facility: 95
city: Budapest
country: Hungary
facility: 13
city: Budapest
country: Hungary
facility: 42
city: Gyula
country: Hungary
facility: 68
city: Kistarcsa
country: Hungary
facility: 100
city: Szeged
country: Hungary
facility: 43
city: Veszprem
country: Hungary
facility: 33
city: Dublin
country: Ireland
facility: 23
city: Dublin
country: Ireland
facility: 51
city: Limerick
country: Ireland
facility: 20
city: Bergamo
country: Italy
facility: 80
city: Genova
country: Italy
facility: 38
city: Genova
country: Italy
facility: 88
city: Magenta
country: Italy
facility: 79
city: Napoli
country: Italy
facility: 98
city: Prato
country: Italy
facility: 67
city: Roma
country: Italy
facility: 36
city: Verona
country: Italy
facility: 39
city: Chihuahua
country: Mexico
facility: 194
city: Chihuahua
country: Mexico
facility: 195
city: Guadalajara
country: Mexico
facility: 193
city: Monterrey
country: Mexico
facility: 192
city: San Luis Potosi
country: Mexico
facility: 191
city: Monaco
country: Monaco
facility: 60
city: Bydgoszcz
country: Poland
facility: 107
city: Poznan
country: Poland
facility: 106
city: Warszawa
country: Poland
facility: 113
city: Warszawa
country: Poland
facility: 115
city: Wroclaw
country: Poland
facility: 108
city: Coimbra
country: Portugal
facility: 69
city: Lisboa
country: Portugal
facility: 76
city: Lisbon
country: Portugal
facility: 27
city: Ponte De Lima
country: Portugal
facility: 14
city: Porto
country: Portugal
facility: 81
city: Bacau
country: Romania
facility: 54
city: Braila
country: Romania
facility: 74
city: Bucharest
country: Romania
facility: 24
city: Bucharest
country: Romania
facility: 25
city: Bucharest
country: Romania
facility: 28
city: Bucharest
country: Romania
facility: 32
city: Bucharest
country: Romania
facility: 57
city: Cluj-Napoca
country: Romania
facility: 12
city: Galati
country: Romania
facility: 96
city: Iasi
country: Romania
facility: 26
city: A Coruna
country: Spain
facility: 16
city: A Coruna
country: Spain
facility: 52
city: Madrid
country: Spain
facility: 30
city: Madrid
country: Spain
facility: 83
city: Sabadell
country: Spain
facility: 82
city: Vigo
country: Spain
facility: 65
city: St. Gallen
country: Switzerland
facility: 53
city: Zürich
country: Switzerland
facility: 50
city: Ashford
country: United Kingdom
facility: 86
city: Brighton
country: United Kingdom
facility: 78
city: Leeds
country: United Kingdom
facility: 59
city: London
country: United Kingdom
facility: 19
city: Poole
country: United Kingdom
facility: 77
city: Sheffield
country: United Kingdom
facility: 55
city: Upton
country: United Kingdom
facility: 73
city: Wigan
country: United Kingdom
facility: 99
Study officials:
affiliation: +1 877 822 9493 (UCB)
name: UCB Cares
role: STUDY_DIRECTOR
References:
citation: 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.
citation: Paul 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.