Evaluation of Sarilumab (SAR153191/REGN88) on Top of Methotrexate in Rheumatoid Arthritis Patients

Rheumatoid Arthritis Clinical Trial

— RA-MOBILITY  

Official title:

A Randomized, Double-blind, Placebo-controlled, Multicenter, Two-part, Dose Ranging and Confirmatory Study With an Operationally Seamless Design, Evaluating Efficacy and Safety of SAR153191 on Top of Methotrexate (MTX) in Patients With Active Rheumatoid Arthritis Who Are Inadequate Responders to MTX Therapy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01061736
• Other study ID #: EFC11072
• Secondary ID: 2009-016266-90
• Status: Completed
• Phase: Phase 2/Phase 3
• First received: February 2, 2010
• Last updated: June 27, 2017
• Start date: March 2010
• Est. completion date: October 2013

Study information

• Verified date: June 2017
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Primary Objectives:

Part A (dose ranging study):

To demonstrate that sarilumab (SAR153191/REGN88) on top of MTX was effective on reduction of signs and symptoms of rheumatoid arthritis at 12 weeks.

Part B (pivotal study):

To demonstrate that sarilumab added to MTX was effective in:

• reduction of signs and symptoms of rheumatoid arthritis at 24 weeks

• inhibition of progression of structural damage at 52 weeks

• improvement in physical function at 16 weeks

Secondary Objectives:

Part B:

To demonstrate that sarilumab added to MTX was effective in induction of a major clinical response at 52 weeks

To assess the safety of sarilumab added to MTX

To document the pharmacokinetic profile of sarilumab added to MTX in participants with active rheumatoid arthritis who were inadequate responders to MTX therapy.

Description:

The total study duration for a participant was 16-22 weeks (Part A) and 56-62 weeks (Part B) broken down as follows:

• Screening: Up to 4 weeks

• Treatment: 12 weeks (Part A) and 52 weeks (Part B)*

• Follow-up: 6 weeks (for participants who would not continue in the long-term extension study).

'*' Participants successfully completing their treatment period would be offered the opportunity to enter the long term extension study LTS11210 (SARIL-RA-EXTEND) (NCT01146652).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1675
• Est. completion date: October 2013
• Est. primary completion date: October 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion criteria :

• Diagnosis of rheumatoid arthritis =3 months duration

• Active disease defined as:

• at least 8/68 tender joints and 6/66 swollen joints,

• high sensitivity C-reactive protein (hs-CRP) >6 mg/l,

• continuous treatment with MTX for at least 12 weeks prior to baseline visit and on stable dose for at least 6 weeks prior to screening visit.

Part B only:

• Bone erosion based on documented X-ray prior to first study drug intake, or

• Cyclic Citrullinated Peptide (CCP) positive, or

• Rheumatoid Factor (RF) positive.

Exclusion criteria:

• Age <18 years or >75 years.

• Treatment with disease-modifying antirheumatic drugs (DMARDs) other than MTX within 4 weeks or 12 weeks prior to screening (depending on DMARDs).

• Past history of non-response to prior Tumor Necrosis Factor (TNF) or biologic treatment.

• Any past or current biologic agents for the treatment of rheumatoid arthritis within 3 months.

• Use of parenteral glucocorticoids or intraarticular glucocorticoids within 4 weeks prior to screening visit.

• Use of oral glucocorticoid greater than 10mg/day or equivalent/day, or a change in dosage within 4 weeks prior to baseline visit.

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

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Drug:
• Sarilumab
Pharmaceutical form: solution for injection Route of administration: subcutaneous
• Placebo (for sarilumab)
Pharmaceutical form: solution for injection Route of administration: subcutaneous
• Methotrexate
Same weekly dose as received prior to enrollment
• Folic Acid
According to local standard

Locations

Country	Name	City	State
Argentina	Investigational Site Number 032005	Buenos Aires
Argentina	Investigational Site Number 032007	Buenos Aires
Argentina	Investigational Site Number 032008	Buenos Aires
Argentina	Investigational Site Number 032006	Caba
Argentina	Investigational Site Number 032002	Cordoba
Argentina	Investigational Site Number 032003	Córdoba
Argentina	Investigational Site Number 032012	Mar Del Plata
Argentina	Investigational Site Number 032011	Quilmes
Argentina	Investigational Site Number 032010	Ramos Mejia
Argentina	Investigational Site Number 032001	Rosario
Argentina	Investigational Site Number 032004	Tucuman
Argentina	Investigational Site Number 032009	Zarate
Australia	Investigational Site Number 036003	Camperdown
Australia	Investigational Site Number 036005	Clayton
Australia	Investigational Site Number 036002	East Malvern
Australia	Investigational Site Number 036012	Fitzroy
Australia	Investigational Site Number 036010	Garran
Australia	Investigational Site Number 036004	Heidelberg West
Australia	Investigational Site Number 036009	Herston
Australia	Investigational Site Number 036001	Maroochydore
Australia	Investigational Site Number 036006	St Leonards
Australia	Investigational Site Number 036011	Sydney
Australia	Investigational Site Number 036014	Victoria Park
Australia	Investigational Site Number 036007	Woodville
Austria	Investigational Site Number 040001	Graz
Austria	Investigational Site Number 040002	Wien
Belarus	Investigational Site Number 112001	Minsk
Belarus	Investigational Site Number 112002	Minsk
Belgium	Investigational Site Number 056003	Genk
Belgium	Investigational Site Number 056001	Liège
Brazil	Investigational Site Number 076008	Campinas
Brazil	Investigational Site Number 076012	Campinas
Brazil	Investigational Site Number 076001	Curitiba
Brazil	Investigational Site Number 076006	Goiania
Brazil	Investigational Site Number 076010	Juiz De Fora
Brazil	Investigational Site Number 076004	Porto Alegre
Brazil	Investigational Site Number 076005	Rio De Janeiro
Brazil	Investigational Site Number 076011	Salvador
Brazil	Investigational Site Number 076002	Sao Paulo
Brazil	Investigational Site Number 076003	Sao Paulo
Brazil	Investigational Site Number 076013	Vitoria
Canada	Investigational Site Number 124004	Burlington
Canada	Investigational Site Number 124003	Mississauga
Canada	Investigational Site Number 124008	Newmarket
Canada	Investigational Site Number 124002	St. Catharines
Canada	Investigational Site Number 124001	Toronto
Canada	Investigational Site Number 124005	Toronto
Canada	Investigational Site Number 124012	Winnipeg
Chile	Investigational Site Number 152005	Osorno
Chile	Investigational Site Number 152010	Puerto Montt
Chile	Investigational Site Number 152001	Santiago
Chile	Investigational Site Number 152002	Santiago
Chile	Investigational Site Number 152008	Santiago
Chile	Investigational Site Number 152009	Santiago
Chile	Investigational Site Number 152011	Santiago
Chile	Investigational Site Number 152012	Santiago
Chile	Investigational Site Number 152013	Santiago
Chile	Investigational Site Number 152014	Talca
Chile	Investigational Site Number 152004	Valdivia
Chile	Investigational Site Number 152006	Vina Del Mar
Chile	Investigational Site Number 152007	Viña Del Mar
Colombia	Investigational Site Number 170004	Barranquilla
Colombia	Investigational Site Number 170001	Bogota
Colombia	Investigational Site Number 170008	Bogota
Colombia	Investigational Site Number 170003	Bogotá
Colombia	Investigational Site Number 170006	Bogotá
Colombia	Investigational Site Number 170007	Bucaramanga
Colombia	Investigational Site Number 170009	Bucaramanga
Colombia	Investigational Site Number 170002	Medellin
Czechia	Investigational Site Number 203005	Brno
Czechia	Investigational Site Number 203004	Hlucin
Czechia	Investigational Site Number 203001	Praha 2
Czechia	Investigational Site Number 203002	Uherske Hradiste
Egypt	Investigational Site Number 818001	Cairo
Egypt	Investigational Site Number 818002	Cairo
Estonia	Investigational Site Number 233001	Tallinn
Estonia	Investigational Site Number 233002	Tallinn
Finland	Investigational Site Number 246001	Helsinki
Finland	Investigational Site Number 246002	Hyvinkää
Finland	Investigational Site Number 246003	Pori
Germany	Investigational Site Number 276007	Berlin
Germany	Investigational Site Number 276008	Berlin
Germany	Investigational Site Number 276004	Erlangen
Germany	Investigational Site Number 276003	Frankfurt Am Main
Germany	Investigational Site Number 276015	Halle/Saale
Germany	Investigational Site Number 276005	Hamburg
Germany	Investigational Site Number 276013	Hamburg
Germany	Investigational Site Number 276012	Heidelberg
Germany	Investigational Site Number 276001	Herne
Germany	Investigational Site Number 276006	Hildesheim
Greece	Investigational Site Number 300001	Athens
Greece	Investigational Site Number 300002	Heraklion
Greece	Investigational Site Number 300003	Thessaloniki
Hungary	Investigational Site Number 348006	Budapest
Hungary	Investigational Site Number 348014	Budapest
Hungary	Investigational Site Number 348003	Debrecen
Hungary	Investigational Site Number 348010	Debrecen
Hungary	Investigational Site Number 348011	Eger
Hungary	Investigational Site Number 348013	Gy?r
Hungary	Investigational Site Number 348005	Sátoraljaújhely
Hungary	Investigational Site Number 348015	Szombathely
Hungary	Investigational Site Number 348004	Veszprém
India	Investigational Site Number 356015	Ahmedabad
India	Investigational Site Number 356007	Bangalore
India	Investigational Site Number 356003	Chennai
India	Investigational Site Number 356005	Hyderabad
India	Investigational Site Number 356012	Hyderabad
India	Investigational Site Number 356011	Lucknow
India	Investigational Site Number 356013	Lucknow
India	Investigational Site Number 356001	Maharashtra
India	Investigational Site Number 356004	Mumbai
India	Investigational Site Number 356010	Mumbai
India	Investigational Site Number 356002	New Delhi
India	Investigational Site Number 356008	New Delhi
Korea, Republic of	Investigational Site Number 410014	Anyang
Korea, Republic of	Investigational Site Number 410006	Busan
Korea, Republic of	Investigational Site Number 410004	Daegu
Korea, Republic of	Investigational Site Number 410013	Daegu
Korea, Republic of	Investigational Site Number 410005	Daejeon
Korea, Republic of	Investigational Site Number 410010	Gwangju
Korea, Republic of	Investigational Site Number 410001	Incheon
Korea, Republic of	Investigational Site Number 410009	Incheon
Korea, Republic of	Investigational Site Number 410011	Jeonju
Korea, Republic of	Investigational Site Number 410002	Seoul
Korea, Republic of	Investigational Site Number 410003	Seoul
Korea, Republic of	Investigational Site Number 410007	Seoul
Korea, Republic of	Investigational Site Number 410012	Seoul
Korea, Republic of	Investigational Site Number 410008	Suwon
Lithuania	Investigational Site Number 440001	Kaunas
Lithuania	Investigational Site Number 440002	Vilnius
Malaysia	Investigational Site Number 458001	Ipoh
Malaysia	Investigational Site Number 458002	Kuching
Malaysia	Investigational Site Number 458003	Putrajaya
Mexico	Investigational Site Number 484008	Durango
Mexico	Investigational Site Number 484002	Guadalajara
Mexico	Investigational Site Number 484004	Merida
Mexico	Investigational Site Number 484009	Merida
Mexico	Investigational Site Number 484007	Metepec
Mexico	Investigational Site Number 484003	Mexico City
Mexico	Investigational Site Number 484001	Mexico, D.F.
Mexico	Investigational Site Number 484005	Monterrey
Netherlands	Investigational Site Number 528002	Heerlen
New Zealand	Investigational Site Number 554004	Christchurch
New Zealand	Investigational Site Number 554002	Rotorua
New Zealand	Investigational Site Number 554003	Tauranga
New Zealand	Investigational Site Number 554001	Timaru
Norway	Investigational Site Number 578004	Kristiansand
Norway	Investigational Site Number 578006	Tønsberg
Philippines	Investigational Site Number 608003	Cebu City
Philippines	Investigational Site Number 608001	Manila
Philippines	Investigational Site Number 608002	Manila
Poland	Investigational Site Number 616002	Bialystok
Poland	Investigational Site Number 616003	Bialystok
Poland	Investigational Site Number 616001	Krakow
Poland	Investigational Site Number 616005	Lublin
Poland	Investigational Site Number 616006	Torun
Poland	Investigational Site Number 616004	Warszawa
Poland	Investigational Site Number 616012	Wroclaw
Portugal	Investigational Site Number 620003	Aveiro
Portugal	Investigational Site Number 620001	Lisboa
Portugal	Investigational Site Number 620002	Lisboa
Romania	Investigational Site Number 642006	Braila
Romania	Investigational Site Number 642004	Bucharest
Romania	Investigational Site Number 642010	Bucharest
Romania	Investigational Site Number 642001	Bucuresti
Romania	Investigational Site Number 642002	Bucuresti
Romania	Investigational Site Number 642003	Bucuresti
Romania	Investigational Site Number 642005	Galati
Romania	Investigational Site Number 642008	Ploiesti
Russian Federation	Investigational Site Number 643006	Kemerovo
Russian Federation	Investigational Site Number 643017	Kemerovo
Russian Federation	Investigational Site Number 643001	Moscow
Russian Federation	Investigational Site Number 643002	Moscow
Russian Federation	Investigational Site Number 643004	Moscow
Russian Federation	Investigational Site Number 643012	Moscow
Russian Federation	Investigational Site Number 643020	Moscow
Russian Federation	Investigational Site Number 643009	Novosibirsk
Russian Federation	Investigational Site Number 643016	Ryazan
Russian Federation	Investigational Site Number 643014	Saint-Petersburg
Russian Federation	Investigational Site Number 643010	Samara
Russian Federation	Investigational Site Number 643011	Saratov
Russian Federation	Investigational Site Number 643007	St-Petersburg
Russian Federation	Investigational Site Number 643008	St-Petersburg
Russian Federation	Investigational Site Number 643013	Ufa
South Africa	Investigational Site Number 710007	Cape Town
South Africa	Investigational Site Number 710009	Cape Town
South Africa	Investigational Site Number 710011	Cape Town
South Africa	Investigational Site Number 710002	Durban
South Africa	Investigational Site Number 710003	Durban
South Africa	Investigational Site Number 710001	Johannesburg
South Africa	Investigational Site Number 710004	Kempton Park
South Africa	Investigational Site Number 710005	Pretoria
South Africa	Investigational Site Number 710006	Pretoria
South Africa	Investigational Site Number 710008	Pretoria
South Africa	Investigational Site Number 710010	Stellenbosch
Spain	Investigational Site Number 724010	Barcelona
Spain	Investigational Site Number 724009	La Coruña
Spain	Investigational Site Number 724011	Sabadell
Spain	Investigational Site Number 724012	Santiago De Compostela
Spain	Investigational Site Number 724007	Sevilla
Taiwan	Investigational Site Number 158002	Linkou
Taiwan	Investigational Site Number 158001	Taipei
Thailand	Investigational Site Number 764001	Bangkok
Thailand	Investigational Site Number 764003	Bangkok
Turkey	Investigational Site Number 792003	Adana
Turkey	Investigational Site Number 792002	Ankara
Turkey	Investigational Site Number 792005	Ankara
Turkey	Investigational Site Number 792004	Antalya
Turkey	Investigational Site Number 792001	Izmir
Ukraine	Investigational Site Number 804003	Dnipropetrovsk
Ukraine	Investigational Site Number 804002	Donetsk
Ukraine	Investigational Site Number 804010	Kharkov
Ukraine	Investigational Site Number 804004	Kyiv
Ukraine	Investigational Site Number 804008	Kyiv
Ukraine	Investigational Site Number 804005	Lviv
Ukraine	Investigational Site Number 804006	Simferopol
Ukraine	Investigational Site Number 804009	Zaporizhzhia
United States	Investigational Site Number 840070	Anniston	Alabama
United States	Investigational Site Number 840003	Atlanta	Georgia
United States	Investigational Site Number 840010	Bethlehem	Pennsylvania
United States	Investigational Site Number 840029	Beverly Hills	California
United States	Investigational Site Number 840004	Birmingham	Alabama
United States	Investigational Site Number 840046	Chicago	Illinois
United States	Investigational Site Number 840058	Columbia	South Carolina
United States	Investigational Site Number 840073	Cumberland	Maryland
United States	Investigational Site Number 840001	Dallas	Texas
United States	Investigational Site Number 840012	Dallas	Texas
United States	Investigational Site Number 840022	Dallas	Texas
United States	Investigational Site Number 840028	Decatur	Georgia
United States	Investigational Site Number 840009	Duncansville	Pennsylvania
United States	Investigational Site Number 840050	Dunedin	Florida
United States	Investigational Site Number 840055	Frederick	Maryland
United States	Investigational Site Number 840072	Gilbert	Arizona
United States	Investigational Site Number 840068	Hickory	North Carolina
United States	Investigational Site Number 840020	Houston	Texas
United States	Investigational Site Number 840018	Idaho Falls	Idaho
United States	Investigational Site Number 840025	Jackson	Tennessee
United States	Investigational Site Number 840041	Jacksonville	Florida
United States	Investigational Site Number 840067	Jupiter	Florida
United States	Investigational Site Number 840015	Lexington	Kentucky
United States	Investigational Site Number 840069	Lubbock	Texas
United States	Investigational Site Number 840027	Marietta	Georgia
United States	Investigational Site Number 840074	Mesquite	Texas
United States	Investigational Site Number 840048	Miami	Florida
United States	Investigational Site Number 840056	New York	New York
United States	Investigational Site Number 840016	North Charleston	South Carolina
United States	Investigational Site Number 840002	Oklahoma City	Oklahoma
United States	Investigational Site Number 840071	Omaha	Nebraska
United States	Investigational Site Number 840006	Orlando	Florida
United States	Investigational Site Number 840007	Palm Desert	California
United States	Investigational Site Number 840063	Palm Harbor	Florida
United States	Investigational Site Number 840062	Reading	Pennsylvania
United States	Investigational Site Number 840066	Saint Louis	Missouri
United States	Investigational Site Number 840008	San Francisco	California
United States	Investigational Site Number 840021	Santa Maria	California
United States	Investigational Site Number 840060	Sarasota	Florida
United States	Investigational Site Number 840061	Tacoma	Washington
United States	Investigational Site Number 840044	Toledo	Ohio
United States	Investigational Site Number 840011	Tulsa	Oklahoma
United States	Investigational Site Number 840065	Tulsa	Oklahoma
United States	Investigational Site Number 840049	Upland	California
United States	Investigational Site Number 840013	Wheaton	Maryland

Sponsors (2)

Lead Sponsor	Collaborator
Sanofi	Regeneron Pharmaceuticals

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Belarus,  Belgium,  Brazil,  Canada,  Chile,  Colombia,  Czechia,  Egypt,  Estonia,  Finland,  Germany,  Greece,  Hungary,  India,  Korea, Republic of,  Lithuania,  Malaysia,  Mexico,  Netherlands,  New Zealand,  Norway,  Philippines,  Poland,  Portugal,  Romania,  Russian Federation,  South Africa,  Spain,  Taiwan,  Thailand,  Turkey,  Ukraine, 

References & Publications (3)

Genovese MC, Fleischmann R, Kivitz AJ, Rell-Bakalarska M, Martincova R, Fiore S, Rohane P, van Hoogstraten H, Garg A, Fan C, van Adelsberg J, Weinstein SP, Graham NM, Stahl N, Yancopoulos GD, Huizinga TW, van der Heijde D. Sarilumab Plus Methotrexate in P — View Citation

Huizinga TW, Fleischmann RM, Jasson M, Radin AR, van Adelsberg J, Fiore S, Huang X, Yancopoulos GD, Stahl N, Genovese MC. Sarilumab, a fully human monoclonal antibody against IL-6Ra in patients with rheumatoid arthritis and an inadequate response to metho — View Citation

Strand V, Kosinski M, Chen CI, Joseph G, Rendas-Baum R, Graham NM, van Hoogstraten H, Bayliss M, Fan C, Huizinga T, Genovese MC. Sarilumab plus methotrexate improves patient-reported outcomes in patients with active rheumatoid arthritis and inadequate responses to methotrexate: results of a phase III trial. Arthritis Res Ther. 2016 Sep 6;18:198. doi: 10.1186/s13075-016-1096-9. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part A: Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response at Week 12	ACR20 response was defined, based on guidelines set forth by the American College of Rheumatology (ACR), as =20 % improvement in tender joint count and swollen joint count as well as =20% improvement in at least 3 of 5 following measures: C-Reactive Protein (CRP), Participant assessment of pain; Participant's global assessment of disease activity; Physician global assessment of disease activity; and Health Assessment Question-Disability Index (HAQ-DI). Missing data imputed by Last Observation Carried Forward (LOCF).	Baseline to Week 12
Primary	Part B: Percentage of Participants Achieving ACR20 Response at Week 24	ACR20 improvement responses were determined without imputation of missing post-baseline values. In addition data collected after treatment discontinuation or rescue was set to missing. Responder status was determined if possible. With these rules, participants automatically became non-responders for all time points beyond the time point they started rescue treatment or discontinued study treatment.	Baseline to Week 24
Primary	Part B: Change From Baseline in Health Assessment Question Disability Index (HAQ-DI) at Week 16	HAQ-DI was a participant-reported questionnaire that assesses the difficulty of performing daily activities: dress/groom, arise, eat, walk, reach, grip, hygiene and common activities. Overall score range from 0=least difficulty to 3=extreme difficulty. An increase in the score indicates a worsening of physical function while a decrease in the score represents improvement. Data collected after treatment discontinuation was set to missing.	Baseline, Week 16
Primary	Part B: Change From Baseline in Van Der Heijde Modified Total Sharp Score (mTSS) at Week 52	The Sharp method modified by D. van der Heijde involves separate scores for erosions and joint space narrowing based on radiographs to assess the degree of structural damage. Total score range from 0 (normal) to 448 (worst possible total score). An increase in total score represents progression of structural damage. Missing data were imputed by the linear extrapolation method.	Baseline, Week 52
Secondary	Part B: Percentage of Participants Achieving a Major Clinical Response at Week 52	Major clinical response was defined as an ACR70 response maintained for at least 24 consecutive weeks. ACR70 response uses the same criteria as for ACR20 but requires 70% improvement. In the primary approach, data collected after treatment discontinuation or rescue was set to missing. No imputation of missing post-baseline values was performed. Responder status was determined if possible. With these rules, participants automatically became non-responders for all time points beyond the time point they started rescue treatment or discontinued study treatment.	Baseline up to Week 52