Clinical trial NCT01764997: An Evaluation of Sarilumab Plus Methotrexate Compared to Etanercept Plus Methotrexate in RA Patients Not Responding to Adalimumab Plus Methotrexate
Official title: A Randomized, Controlled Study of Sarilumab and Methotrexate (MTX) Versus Etanercept and MTX in Patients With Rheumatoid Arthritis (RA) and an Inadequate Response to 4 Months of Treatment With Adalimumab and MTX
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Rheumatoid Arthritis
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
Collaborators: name: Regeneron Pharmaceuticals
First posted: 2013-01-10
Enrollment: 776
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: Primary Objective:

To demonstrate the treatment effect of sarilumab and methotrexate (MTX) compared to etanercept and MTX in participants with rheumatoid arthritis (RA) and an inadequate response to adalimumab and MTX by evaluation of the Disease Activity Score for 28 joints (DAS28).

Secondary Objectives:

To assess the signs and symptoms of RA in participants taking sarilumab in combination with MTX.

To assess the quality of life of participants with RA taking sarilumab in combination with MTX.

To assess the safety and tolerability of sarilumab in combination with MTX in participants with RA.

Detailed description: The maximum study duration per participant enrolled in the open label run-in phase and was eligible to enroll in the randomized phase of main study was 54 weeks:

* open label screening period of up to 4 weeks
* open-label treatment period of 16 weeks
* randomized screening period of 2 to 4 weeks
* randomized treatment post-treatment safety follow-up period of 6 weeks.

The maximum study duration per participant enrolled only in the open label run-in phase and was not eligible to enroll in the randomized phase of main study was 26 weeks:

* open label screening period of up to 4 weeks
* open-label treatment period of 16 weeks
* open label treatment post-treatment safety follow-up period of 6 weeks.

The maximum study duration per participant enrolled in the open label run-in phase and was eligible to enroll in the sarilumab sub-study was 82 weeks:

* open label screening period of up to 4 weeks
* open-label treatment period of 16 weeks
* screening period of 2 to 4 weeks
* sarilumab treatment period of 52 weeks
* sub-study post-treatment safety follow-up period of 6 weeks.

Eligibility criteria: Inclusion criteria:

* Diagnosis of RA \>/= 3 months duration.
* Continuous treatment of MTX 10 - 25 mg/week (or per local labeling requirements if the dose range differs) for at least 12 weeks before screening visit and on a stable dose for 8 weeks before screening visit.
* Active disease defined as: at least 6/66 swollen and 8/68 tender joints and high sensitivity C-reactive protein \> 10 mg/L.

Exclusion criteria:

* Age \< 18 years.
* Use of parenteral corticosteroids or intra-articular corticosteroids within 4 weeks of the screening visit.
* Use of oral corticosteroids in a dose higher than prednisone 10 mg or equivalent per day, or a change in dosage within 4 weeks of the screening visit.
* Prior treatment with a tumor necrosis factor (TNF)-alpha inhibitor, or other biological disease modifying anti-rheumatoid drug (DMARD) or Janus Kinase inhibitor.
* New treatment with or dose-adjustment of on-going nonsteroidal anti-inflammatory drugs (NSAIDs) or cyclo-oxygenase-2 (COX-2) inhibitors within 4 weeks of the screening visit.
* Treatment with traditional oral DMARD /immunosuppressive agents other than MTX within 4 weeks or 12 weeks before the screening visit, depending on DMARD.

The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Primary outcomes:
measure: Change From Baseline in Disease Activity Score for 28 Joints - C-Reactive Protein (DAS28-CRP) Score at Week 24
timeFrame: Baseline, Week 24
Secondary outcomes:
measure: Number of Participants With at Least 20% Improvement in American College of Rheumatology (ACR20), at Least 50% Improvement in ACR (ACR50) and at Least 70% Improvement in ACR (ACR70) Efficacy Response Rates at Week 12 and Week 24
timeFrame: Week 12 and Week 24
measure: Percentage of Participants Achieving Clinical Remission Score (DAS28-CRP) <2.6 at Week 12 and Week 24
timeFrame: Week 12 and Week 24
measure: Change From Baseline in DAS28-CRP Score at Week 12
timeFrame: Baseline, Week 12
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Investigational Site Number 840004
state: Alabama
city: Glendale
country: United States
facility: Investigational Site Number 840212
state: California
city: Thousand Oaks
country: United States
facility: Investigational Site Number 840211
state: California
city: Upland
country: United States
facility: Investigational Site Number 840049
state: California
city: Victorville
country: United States
facility: Investigational Site Number 840205
state: California
city: Denver
country: United States
facility: Investigational Site Number 840201
state: Colorado
city: Danbury
country: United States
facility: Investigational Site Number 840209
state: Connecticut
city: Washington, D.C.
country: United States
facility: Investigational Site Number 840203
state: District of Columbia
city: Clearwater
country: United States
facility: Investigational Site Number 840210
state: Florida
city: Ormond Beach
country: United States
facility: Investigational Site Number 840128
state: Florida
city: Palm Harbor
country: United States
facility: Investigational Site Number 840063
state: Florida
city: Sarasota
country: United States
facility: Investigational Site Number 840060
state: Florida
city: Tampa
country: United States
facility: Investigational Site Number 840207
state: Florida
city: Idaho Falls
country: United States
facility: Investigational Site Number 840018
state: Idaho
city: Indianapolis
country: United States
facility: Investigational Site Number 840213
state: Indiana
city: Lake Charles
country: United States
facility: Investigational Site Number 840109
state: Louisiana
city: Cumberland
country: United States
facility: Investigational Site Number 840073
state: Maryland
city: Hagerstown
country: United States
facility: Investigational Site Number 840202
state: Maryland
city: Battle Creek
country: United States
facility: Investigational Site Number 840204
state: Michigan
city: Lansing
country: United States
facility: Investigational Site Number 840150
state: Michigan
city: Jackson
country: United States
facility: Investigational Site Number 840200
state: Mississippi
city: Tupelo
country: United States
facility: Investigational Site Number 840037
state: Mississippi
city: Lincoln
country: United States
facility: Investigational Site Number 840112
state: Nebraska
city: New York
country: United States
facility: Investigational Site Number 840056
state: New York
city: Pittsburgh
country: United States
facility: Investigational Site Number 840117
state: Pennsylvania
city: North Charleston
country: United States
facility: Investigational Site Number 840016
state: South Carolina
city: Jackson
country: United States
facility: Investigational Site Number 840025
state: Tennessee
city: Mesquite
country: United States
facility: Investigational Site Number 840074
state: Texas
city: Tacoma
country: United States
facility: Investigational Site Number 840061
state: Washington
city: Clarksburg
country: United States
facility: Investigational Site Number 840124
state: West Virginia
city: Buenos Aires
country: Argentina
facility: Investigational Site Number 032052
city: Buenos Aires
country: Argentina
facility: Investigational Site Number 032050
city: La Plata
country: Argentina
facility: Investigational Site Number 032053
city: Rosario
country: Argentina
facility: Investigational Site Number 032013
city: San Miguel De Tucumán
country: Argentina
facility: Investigational Site Number 032051
city: Tucuman
country: Argentina
facility: Investigational Site Number 032005
city: Zarate
country: Argentina
facility: Investigational Site Number 032009
city: Camperdown
country: Australia
facility: Investigational Site Number 036020
city: Heidelberg West
country: Australia
facility: Investigational Site Number 036004
city: Victoria Park
country: Australia
facility: Investigational Site Number 036014
city: Woodville
country: Australia
facility: Investigational Site Number 036007
city: Curitiba
country: Brazil
facility: Investigational Site Number 076001
city: Curitiba
country: Brazil
facility: Investigational Site Number 076016
city: Goiania
country: Brazil
facility: Investigational Site Number 076006
city: Juiz De Fora
country: Brazil
facility: Investigational Site Number 076010
city: Rio De Janeiro
country: Brazil
facility: Investigational Site Number 076005
city: Vitoria
country: Brazil
facility: Investigational Site Number 076013
city: Osorno
country: Chile
facility: Investigational Site Number 152005
city: Santiago
country: Chile
facility: Investigational Site Number 152018
city: Santiago
country: Chile
facility: Investigational Site Number 152001
city: Santiago
country: Chile
facility: Investigational Site Number 152002
city: Santiago
country: Chile
facility: Investigational Site Number 152011
city: Temuco
country: Chile
facility: Investigational Site Number 152015
city: Bogota
country: Colombia
facility: Investigational Site Number 170016
city: Bogota
country: Colombia
facility: Investigational Site Number 170001
city: Bogotá
country: Colombia
facility: Investigational Site Number 170040
city: Bucaramanga
country: Colombia
facility: Investigational Site Number 170007
city: Bucaramanga
country: Colombia
facility: Investigational Site Number 170009
city: Medellin
country: Colombia
facility: Investigational Site Number 170041
city: Ostrava
country: Czechia
facility: Investigational Site Number 203004
city: Praha 2
country: Czechia
facility: Investigational Site Number 203001
city: Praha 4
country: Czechia
facility: Investigational Site Number 203031
city: Praha 4
country: Czechia
facility: Investigational Site Number 203033
city: Praha 4
country: Czechia
facility: Investigational Site Number 203030
city: Praha
country: Czechia
facility: Investigational Site Number 203032
city: Uherske Hradiste
country: Czechia
facility: Investigational Site Number 203002
city: Zlin
country: Czechia
facility: Investigational Site Number 203006
city: Cuenca
country: Ecuador
facility: Investigational Site Number 218003
city: Guayaquil
country: Ecuador
facility: Investigational Site Number 218001
city: Quito
country: Ecuador
facility: Investigational Site Number 218002
city: Helsinki
country: Finland
facility: Investigational Site Number 246001
city: Hyvinkää
country: Finland
facility: Investigational Site Number 246002
city: Oulu
country: Finland
facility: Investigational Site Number 246030
city: Pori
country: Finland
facility: Investigational Site Number 246003
city: Tampere
country: Finland
facility: Investigational Site Number 246032
city: Amiens Cedex 1
country: France
facility: Investigational Site Number 250003
city: Bobigny
country: France
facility: Investigational Site Number 250007
city: La Roche Sur Yon Cedex 9
country: France
facility: Investigational Site Number 250001
city: Montpellier
country: France
facility: Investigational Site Number 250002
city: Paris Cedex 4
country: France
facility: Investigational Site Number 250004
city: Paris
country: France
facility: Investigational Site Number 250005
city: Strasbourg
country: France
facility: Investigational Site Number 250006
city: Toulouse
country: France
facility: Investigational Site Number 250008
city: Berlin
country: Germany
facility: Investigational Site Number 276007
city: Berlin
country: Germany
facility: Investigational Site Number 276057
city: Dresden
country: Germany
facility: Investigational Site Number 276056
city: Dresden
country: Germany
facility: Investigational Site Number 276055
city: Erlangen
country: Germany
facility: Investigational Site Number 276051
city: Hamburg
country: Germany
facility: Investigational Site Number 276013
city: Herne
country: Germany
facility: Investigational Site Number 276001
city: Koeln
country: Germany
facility: Investigational Site Number 276058
city: Ludwigsfelde
country: Germany
facility: Investigational Site Number 276053
city: Rostock
country: Germany
facility: Investigational Site Number 276050
city: Athens
country: Greece
facility: Investigational Site Number 300010
city: Heraklion
country: Greece
facility: Investigational Site Number 300002
city: N. Efkarpia
country: Greece
facility: Investigational Site Number 300014
city: Patras
country: Greece
facility: Investigational Site Number 300012
city: Budapest
country: Hungary
facility: Investigational Site Number 348001
city: Debrecen
country: Hungary
facility: Investigational Site Number 348010
city: Esztergom
country: Hungary
facility: Investigational Site Number 348021
city: Gy?r
country: Hungary
facility: Investigational Site Number 348013
city: Gyula
country: Hungary
facility: Investigational Site Number 348008
city: Ashkelon
country: Israel
facility: Investigational Site Number 376032
city: Haifa
country: Israel
facility: Investigational Site Number 376001
city: Haifa
country: Israel
facility: Investigational Site Number 376010
city: Haifa
country: Israel
facility: Investigational Site Number 376031
city: Jerusalem
country: Israel
facility: Investigational Site Number 376035
city: Ramat Gan
country: Israel
facility: Investigational Site Number 376030
city: Tel Aviv
country: Israel
facility: Investigational Site Number 376011
city: Tel Hashomer
country: Israel
facility: Investigational Site Number 376034
city: Firenze
country: Italy
facility: Investigational Site Number 380002
city: Genova
country: Italy
facility: Investigational Site Number 380004
city: Genova
country: Italy
facility: Investigational Site Number 380005
city: L'Aquila
country: Italy
facility: Investigational Site Number 380041
city: Valeggio Sul Mincio
country: Italy
facility: Investigational Site Number 380042
city: Busan
country: Korea, Republic of
facility: Investigational Site Number 410020
city: Busan
country: Korea, Republic of
facility: Investigational Site Number 410006
city: Daegu
country: Korea, Republic of
facility: Investigational Site Number 410013
city: Daejeon
country: Korea, Republic of
facility: Investigational Site Number 410005
city: Jeonju
country: Korea, Republic of
facility: Investigational Site Number 410011
city: Seoul
country: Korea, Republic of
facility: Investigational Site Number 410016
city: Seoul
country: Korea, Republic of
facility: Investigational Site Number 410015
city: Seoul
country: Korea, Republic of
facility: Investigational Site Number 410022
city: Seoul
country: Korea, Republic of
facility: Investigational Site Number 410023
city: Seoul
country: Korea, Republic of
facility: Investigational Site Number 410021
city: Suwon
country: Korea, Republic of
facility: Investigational Site Number 410008
city: Liepaja
country: Latvia
facility: Investigational Site Number 428002
city: Riga
country: Latvia
facility: Investigational Site Number 428001
city: Ventspils
country: Latvia
facility: Investigational Site Number 428003
city: Kaunas
country: Lithuania
facility: Investigational Site Number 440005
city: Klaipeda
country: Lithuania
facility: Investigational Site Number 440006
city: Panevezys
country: Lithuania
facility: Investigational Site Number 440010
city: Vilnius
country: Lithuania
facility: Investigational Site Number 440011
city: Batu Caves
country: Malaysia
facility: Investigational Site Number 458012
city: Georgetown
country: Malaysia
facility: Investigational Site Number 458014
city: Ipoh
country: Malaysia
facility: Investigational Site Number 458001
city: Kota Bharu
country: Malaysia
facility: Investigational Site Number 458013
city: Kuching
country: Malaysia
facility: Investigational Site Number 458002
city: Melaka
country: Malaysia
facility: Investigational Site Number 458010
city: Seremban
country: Malaysia
facility: Investigational Site Number 458011
city: Cd. Obregon
country: Mexico
facility: Investigational Site Number 484027
city: Chihuahua
country: Mexico
facility: Investigational Site Number 484023
city: Deleg. Benito Juárez
country: Mexico
facility: Investigational Site Number 484029
city: Guadalajara
country: Mexico
facility: Investigational Site Number 484013
city: Guadalajara
country: Mexico
facility: Investigational Site Number 484018
city: Merida
country: Mexico
facility: Investigational Site Number 484004
city: Mexicali
country: Mexico
facility: Investigational Site Number 484010
city: Mexicali
country: Mexico
facility: Investigational Site Number 484026
city: Mexico City
country: Mexico
facility: Investigational Site Number 484052
city: México
country: Mexico
facility: Investigational Site Number 484017
city: San Luis
country: Mexico
facility: Investigational Site Number 484025
city: Tijuana
country: Mexico
facility: Investigational Site Number 484051
city: Auckland
country: New Zealand
facility: Investigational Site Number 554007
city: Dunedin
country: New Zealand
facility: Investigational Site Number 554010
city: Hamilton
country: New Zealand
facility: Investigational Site Number 554005
city: Nelson
country: New Zealand
facility: Investigational Site Number 554011
city: Lima
country: Peru
facility: Investigational Site Number 604001
city: Lima
country: Peru
facility: Investigational Site Number 604010
city: Lima
country: Peru
facility: Investigational Site Number 604009
city: Lima
country: Peru
facility: Investigational Site Number 604012
city: Lima
country: Peru
facility: Investigational Site Number 604007
city: Lima
country: Peru
facility: Investigational Site Number 604005
city: Lima
country: Peru
facility: Investigational Site Number 604020
city: Bydgoszcz
country: Poland
facility: Investigational Site Number 616019
city: Bytom
country: Poland
facility: Investigational Site Number 616054
city: Dzialdowo
country: Poland
facility: Investigational Site Number 616052
city: Elblag
country: Poland
facility: Investigational Site Number 616015
city: Krakow
country: Poland
facility: Investigational Site Number 616057
city: Krakow
country: Poland
facility: Investigational Site Number 616059
city: Krakow
country: Poland
facility: Investigational Site Number 616061
city: Lublin
country: Poland
facility: Investigational Site Number 616005
city: Myslenice
country: Poland
facility: Investigational Site Number 616063
city: Poznan
country: Poland
facility: Investigational Site Number 616018
city: Sosnowiec
country: Poland
facility: Investigational Site Number 616013
city: Starachowice
country: Poland
facility: Investigational Site Number 616056
city: Szczecin
country: Poland
facility: Investigational Site Number 616016
city: Ustron
country: Poland
facility: Investigational Site Number 616058
city: Warszawa
country: Poland
facility: Investigational Site Number 616051
city: Zyrardow
country: Poland
facility: Investigational Site Number 616053
city: Bacau
country: Romania
facility: Investigational Site Number 642041
city: Bucharest
country: Romania
facility: Investigational Site Number 642012
city: Bucharest
country: Romania
facility: Investigational Site Number 642004
city: Bucharest
country: Romania
facility: Investigational Site Number 642023
city: Bucuresti
country: Romania
facility: Investigational Site Number 642001
city: Bucuresti
country: Romania
facility: Investigational Site Number 642040
city: Bucuresti
country: Romania
facility: Investigational Site Number 642002
city: Bucuresti
country: Romania
facility: Investigational Site Number 642042
city: Galati
country: Romania
facility: Investigational Site Number 642005
city: Iasi
country: Romania
facility: Investigational Site Number 642013
city: Iasi
country: Romania
facility: Investigational Site Number 642014
city: Targoviste
country: Romania
facility: Investigational Site Number 642022
city: Kemerovo
country: Russian Federation
facility: Investigational Site Number 643006
city: Krasnoyarsk
country: Russian Federation
facility: Investigational Site Number 643056
city: Moscow
country: Russian Federation
facility: Investigational Site Number 643052
city: Moscow
country: Russian Federation
facility: Investigational Site Number 643021
city: Moscow
country: Russian Federation
facility: Investigational Site Number 643031
city: Moscow
country: Russian Federation
facility: Investigational Site Number 643030
city: Novosibirsk
country: Russian Federation
facility: Investigational Site Number 643022
city: Samara
country: Russian Federation
facility: Investigational Site Number 643010
city: Saratov
country: Russian Federation
facility: Investigational Site Number 643011
city: Smolensk
country: Russian Federation
facility: Investigational Site Number 643059
city: St-Petersburg
country: Russian Federation
facility: Investigational Site Number 643008
city: St. Peterburg
country: Russian Federation
facility: Investigational Site Number 643058
city: Ufa
country: Russian Federation
facility: Investigational Site Number 643013
city: Voronezh
country: Russian Federation
facility: Investigational Site Number 643050
city: Yaroslavl
country: Russian Federation
facility: Investigational Site Number 643057
city: Yaroslavl
country: Russian Federation
facility: Investigational Site Number 643051
city: Cape Town
country: South Africa
facility: Investigational Site Number 710011
city: Cape Town
country: South Africa
facility: Investigational Site Number 710007
city: Pretoria
country: South Africa
facility: Investigational Site Number 710008
city: Pretoria
country: South Africa
facility: Investigational Site Number 710006
city: Stellenbsoch
country: South Africa
facility: Investigational Site Number 710010
city: Córdoba
country: Spain
facility: Investigational Site Number 724043
city: La Coruña
country: Spain
facility: Investigational Site Number 724009
city: Madrid
country: Spain
facility: Investigational Site Number 724042
city: Madrid
country: Spain
facility: Investigational Site Number 724041
city: Madrid
country: Spain
facility: Investigational Site Number 724040
city: Málaga
country: Spain
facility: Investigational Site Number 724001
city: Sabadell
country: Spain
facility: Investigational Site Number 724011
city: Santiago De Compostela
country: Spain
facility: Investigational Site Number 724012
city: Changhua
country: Taiwan
facility: Investigational Site Number 158010
city: Chia-Yi
country: Taiwan
facility: Investigational Site Number 158004
city: Kaohsiung
country: Taiwan
facility: Investigational Site Number 158012
city: Kaohsiung
country: Taiwan
facility: Investigational Site Number 158011
city: Taipei
country: Taiwan
facility: Investigational Site Number 158006
city: Bangkok-Noi
country: Thailand
facility: Investigational Site Number 764003
city: Bangkok
country: Thailand
facility: Investigational Site Number 764002
city: Bangkok
country: Thailand
facility: Investigational Site Number 764010
city: Khon Kaen
country: Thailand
facility: Investigational Site Number 764011
city: Dnipropetrovsk
country: Ukraine
facility: Investigational Site Number 804003
city: Donetsk
country: Ukraine
facility: Investigational Site Number 804002
city: Donetsk
country: Ukraine
facility: Investigational Site Number 804024
city: Ivano-Frankivsk
country: Ukraine
facility: Investigational Site Number 804029
city: Kharkiv
country: Ukraine
facility: Investigational Site Number 804010
city: Kharkov
country: Ukraine
facility: Investigational Site Number 804001
city: Kiev
country: Ukraine
facility: Investigational Site Number 804025
city: Kyiv
country: Ukraine
facility: Investigational Site Number 804023
city: Kyiv
country: Ukraine
facility: Investigational Site Number 804014
city: Kyiv
country: Ukraine
facility: Investigational Site Number 804027
city: Kyiv
country: Ukraine
facility: Investigational Site Number 804011
city: Lutsk
country: Ukraine
facility: Investigational Site Number 804030
city: Lviv
country: Ukraine
facility: Investigational Site Number 804005
city: Lviv
country: Ukraine
facility: Investigational Site Number 804033
city: Lviv
country: Ukraine
facility: Investigational Site Number 804020
city: Odesa
country: Ukraine
facility: Investigational Site Number 804032
city: Odesa
country: Ukraine
facility: Investigational Site Number 804022
city: Odessa
country: Ukraine
facility: Investigational Site Number 804012
city: Simferopol
country: Ukraine
facility: Investigational Site Number 804021
city: Zaporozhye
country: Ukraine
facility: Investigational Site Number 804028
city: Zhytomyr
country: Ukraine
facility: Investigational Site Number 804031
city: Barnsley
country: United Kingdom
facility: Investigational Site Number 826023
city: Birmingham
country: United Kingdom
facility: Investigational Site Number 826022
city: Dudley
country: United Kingdom
facility: Investigational Site Number 826021
city: Durham
country: United Kingdom
facility: Investigational Site Number 826026
city: Durham
country: United Kingdom
facility: Investigational Site Number 826027
city: Harlow
country: United Kingdom
facility: Investigational Site Number 826020
city: Wigan
country: United Kingdom
facility: Investigational Site Number 826025
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: