Evaluation of Sarilumab (SAR153191/REGN88) on Top of Methotrexate in Rheumatoid Arthritis Patients
- Conditions
- Rheumatoid Arthritis
- Interventions
- Registration Number
- NCT01061736
- Lead Sponsor
- Sanofi
- Brief 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.
- Detailed 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 & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 1675
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Part B: SAR 150 mg q2w (Cohort 1[Selected Dose]+Cohort 2) Sarilumab Sarilumab 150 mg SC injection q2w on top of MTX for a maximum of 52 weeks. Participants with inadequate response from Week 16 could be rescued with open-label highest dose of sarilumab. Part A: SAR 100 mg q2w Folic Acid Sarilumab 100 mg SC injection every other week (q2w) alternating with placebo on top of MTX for 12 weeks. Part A: SAR 100 mg qw Folic Acid Sarilumab 100 mg subcutaneous (SC) injection weekly (qw) on top of MTX for 12 weeks. Part A: SAR 150 mg qw Folic Acid Sarilumab 150 mg SC injection qw on top of MTX for 12 weeks. Part A: SAR 100 mg q2w Methotrexate Sarilumab 100 mg SC injection every other week (q2w) alternating with placebo on top of MTX for 12 weeks. Part A: Placebo qw Folic Acid Placebo (for sarilumab) qw on top of MTX for 12 weeks. Part B Cohort 1: Non-selected Doses Sarilumab Sarilumab 100 mg qw, 150 mg qw or 100 mg q2w SC injections as in Part A on top of MTX up to dose selection. After dose selection, participants were not continued but were allowed to participate in the open-label, long-term, extension study SARIL-RA-EXTEND (LTS11210). Part A: SAR 150 mg q2w Sarilumab Sarilumab 150 mg SC injection q2w alternating with placebo on top of MTX for 12 weeks. Part A: SAR 150 mg q2w Placebo (for sarilumab) Sarilumab 150 mg SC injection q2w alternating with placebo on top of MTX for 12 weeks. Part A: SAR 100 mg q2w Sarilumab Sarilumab 100 mg SC injection every other week (q2w) alternating with placebo on top of MTX for 12 weeks. Part A: SAR 200 mg q2w Methotrexate Sarilumab 200 mg SC injection q2w alternating with placebo on top of MTX for 12 weeks. Part B Cohort 1: Non-selected Doses Placebo (for sarilumab) Sarilumab 100 mg qw, 150 mg qw or 100 mg q2w SC injections as in Part A on top of MTX up to dose selection. After dose selection, participants were not continued but were allowed to participate in the open-label, long-term, extension study SARIL-RA-EXTEND (LTS11210). Part A: SAR 100 mg q2w Placebo (for sarilumab) Sarilumab 100 mg SC injection every other week (q2w) alternating with placebo on top of MTX for 12 weeks. Part A: Placebo qw Placebo (for sarilumab) Placebo (for sarilumab) qw on top of MTX for 12 weeks. Part B: Placebo q2w (Cohort 1[Selected Dose]+Cohort 2) Placebo (for sarilumab) Placebo (for sarilumab) q2w on top of MTX for a maximum of 52 weeks. Participants with inadequate response from Week 16 could be rescued with open-label highest dose of sarilumab. Part A: SAR 150 mg q2w Methotrexate Sarilumab 150 mg SC injection q2w alternating with placebo on top of MTX for 12 weeks. Part A: Placebo qw Methotrexate Placebo (for sarilumab) qw on top of MTX for 12 weeks. Part A: SAR 200 mg q2w Placebo (for sarilumab) Sarilumab 200 mg SC injection q2w alternating with placebo on top of MTX for 12 weeks. Part B: Placebo q2w (Cohort 1[Selected Dose]+Cohort 2) Methotrexate Placebo (for sarilumab) q2w on top of MTX for a maximum of 52 weeks. Participants with inadequate response from Week 16 could be rescued with open-label highest dose of sarilumab. Part A: SAR 150 mg qw Methotrexate Sarilumab 150 mg SC injection qw on top of MTX for 12 weeks. Part A: SAR 100 mg qw Sarilumab Sarilumab 100 mg subcutaneous (SC) injection weekly (qw) on top of MTX for 12 weeks. Part A: SAR 100 mg qw Methotrexate Sarilumab 100 mg subcutaneous (SC) injection weekly (qw) on top of MTX for 12 weeks. Part A: SAR 150 mg qw Sarilumab Sarilumab 150 mg SC injection qw on top of MTX for 12 weeks. Part A: SAR 200 mg q2w Sarilumab Sarilumab 200 mg SC injection q2w alternating with placebo on top of MTX for 12 weeks. Part A: SAR 150 mg q2w Folic Acid Sarilumab 150 mg SC injection q2w alternating with placebo on top of MTX for 12 weeks. Part A: SAR 200 mg q2w Folic Acid Sarilumab 200 mg SC injection q2w alternating with placebo on top of MTX for 12 weeks. Part B Cohort 1: Non-selected Doses Folic Acid Sarilumab 100 mg qw, 150 mg qw or 100 mg q2w SC injections as in Part A on top of MTX up to dose selection. After dose selection, participants were not continued but were allowed to participate in the open-label, long-term, extension study SARIL-RA-EXTEND (LTS11210). Part B Cohort 1: Non-selected Doses Methotrexate Sarilumab 100 mg qw, 150 mg qw or 100 mg q2w SC injections as in Part A on top of MTX up to dose selection. After dose selection, participants were not continued but were allowed to participate in the open-label, long-term, extension study SARIL-RA-EXTEND (LTS11210). Part B: SAR 150 mg q2w (Cohort 1[Selected Dose]+Cohort 2) Methotrexate Sarilumab 150 mg SC injection q2w on top of MTX for a maximum of 52 weeks. Participants with inadequate response from Week 16 could be rescued with open-label highest dose of sarilumab. Part B: SAR 150 mg q2w (Cohort 1[Selected Dose]+Cohort 2) Folic Acid Sarilumab 150 mg SC injection q2w on top of MTX for a maximum of 52 weeks. Participants with inadequate response from Week 16 could be rescued with open-label highest dose of sarilumab. Part B: SAR 200 mg q2w (Cohort 1[Selected Dose]+Cohort 2) Methotrexate Sarilumab 200 mg SC injection q2w on top of MTX for a maximum of 52 weeks. Participants with inadequate response from Week 16 could be rescued with open-label highest dose of sarilumab. Part B: SAR 200 mg q2w (Cohort 1[Selected Dose]+Cohort 2) Sarilumab Sarilumab 200 mg SC injection q2w on top of MTX for a maximum of 52 weeks. Participants with inadequate response from Week 16 could be rescued with open-label highest dose of sarilumab. Part B: SAR 200 mg q2w (Cohort 1[Selected Dose]+Cohort 2) Folic Acid Sarilumab 200 mg SC injection q2w on top of MTX for a maximum of 52 weeks. Participants with inadequate response from Week 16 could be rescued with open-label highest dose of sarilumab. Part B: Placebo q2w (Cohort 1[Selected Dose]+Cohort 2) Folic Acid Placebo (for sarilumab) q2w on top of MTX for a maximum of 52 weeks. Participants with inadequate response from Week 16 could be rescued with open-label highest dose of sarilumab.
- Primary Outcome Measures
Name Time Method Part A: Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response at Week 12 Baseline to 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).
Part B: Percentage of Participants Achieving ACR20 Response at Week 24 Baseline to 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.
Part B: Change From Baseline in Health Assessment Question Disability Index (HAQ-DI) at Week 16 Baseline, 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.
Part B: Change From Baseline in Van Der Heijde Modified Total Sharp Score (mTSS) at Week 52 Baseline, 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.
- Secondary Outcome Measures
Name Time Method Part B: Percentage of Participants Achieving a Major Clinical Response at Week 52 Baseline up to 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.
Trial Locations
- Locations (262)
Investigational Site Number 032002
🇦🇷Cordoba, Argentina
Investigational Site Number 032004
🇦🇷Tucuman, Argentina
Investigational Site Number 032003
🇦🇷Córdoba, Argentina
Investigational Site Number 032012
🇦🇷Mar Del Plata, Argentina
Investigational Site Number 032010
🇦🇷Ramos Mejia, Argentina
Investigational Site Number 032001
🇦🇷Rosario, Argentina
Investigational Site Number 112002
🇧🇾Minsk, Belarus
Investigational Site Number 300002
🇬🇷Heraklion, Greece
Investigational Site Number 348003
🇭🇺Debrecen, Hungary
Investigational Site Number 356005
🇮🇳Hyderabad, India
Investigational Site Number 356011
🇮🇳Lucknow, India
Investigational Site Number 356001
🇮🇳Maharashtra, India
Investigational Site Number 356008
🇮🇳New Delhi, India
Investigational Site Number 440002
🇱🇹Vilnius, Lithuania
Investigational Site Number 458002
🇲🇾Kuching, Malaysia
Investigational Site Number 458003
🇲🇾Putrajaya, Malaysia
Investigational Site Number 484002
🇲🇽Guadalajara, Mexico
Investigational Site Number 484009
🇲🇽Merida, Mexico
Investigational Site Number 608001
🇵🇭Manila, Philippines
Investigational Site Number 616002
🇵🇱Bialystok, Poland
Investigational Site Number 643007
🇷🇺St-Petersburg, Russian Federation
Investigational Site Number 804005
🇺🇦Lviv, Ukraine
Investigational Site Number 804006
🇺🇦Simferopol, Ukraine
Investigational Site Number 840003
🇺🇸Atlanta, Georgia, United States
Investigational Site Number 840046
🇺🇸Chicago, Illinois, United States
Investigational Site Number 840001
🇺🇸Dallas, Texas, United States
Investigational Site Number 840012
🇺🇸Dallas, Texas, United States
Investigational Site Number 840020
🇺🇸Houston, Texas, United States
Investigational Site Number 840070
🇺🇸Anniston, Alabama, United States
Investigational Site Number 840029
🇺🇸Beverly Hills, California, United States
Investigational Site Number 840072
🇺🇸Gilbert, Arizona, United States
Investigational Site Number 840027
🇺🇸Marietta, Georgia, United States
Investigational Site Number 840028
🇺🇸Decatur, Georgia, United States
Investigational Site Number 840018
🇺🇸Idaho Falls, Idaho, United States
Investigational Site Number 840015
🇺🇸Lexington, Kentucky, United States
Investigational Site Number 840066
🇺🇸Saint Louis, Missouri, United States
Investigational Site Number 840056
🇺🇸New York, New York, United States
Investigational Site Number 840068
🇺🇸Hickory, North Carolina, United States
Investigational Site Number 840044
🇺🇸Toledo, Ohio, United States
Investigational Site Number 840009
🇺🇸Duncansville, Pennsylvania, United States
Investigational Site Number 840065
🇺🇸Tulsa, Oklahoma, United States
Investigational Site Number 840010
🇺🇸Bethlehem, Pennsylvania, United States
Investigational Site Number 840011
🇺🇸Tulsa, Oklahoma, United States
Investigational Site Number 840062
🇺🇸Reading, Pennsylvania, United States
Investigational Site Number 032011
🇦🇷Quilmes, Argentina
Investigational Site Number 036011
🇦🇺Sydney, Australia
Investigational Site Number 036001
🇦🇺Maroochydore, Australia
Investigational Site Number 036014
🇦🇺Victoria Park, Australia
Investigational Site Number 076006
🇧🇷Goiania, Brazil
Investigational Site Number 076004
🇧🇷Porto Alegre, Brazil
Investigational Site Number 076002
🇧🇷Sao Paulo, Brazil
Investigational Site Number 076013
🇧🇷Vitoria, Brazil
Investigational Site Number 124001
🇨🇦Toronto, Canada
Investigational Site Number 124008
🇨🇦Newmarket, Canada
Investigational Site Number 124003
🇨🇦Mississauga, Canada
Investigational Site Number 124005
🇨🇦Toronto, Canada
Investigational Site Number 124002
🇨🇦St. Catharines, Canada
Investigational Site Number 152005
🇨🇱Osorno, Chile
Investigational Site Number 152010
🇨🇱Puerto Montt, Chile
Investigational Site Number 152009
🇨🇱Santiago, Chile
Investigational Site Number 152001
🇨🇱Santiago, Chile
Investigational Site Number 152007
🇨🇱Viña Del Mar, Chile
Investigational Site Number 170004
🇨🇴Barranquilla, Colombia
Investigational Site Number 170001
🇨🇴Bogota, Colombia
Investigational Site Number 170009
🇨🇴Bucaramanga, Colombia
Investigational Site Number 276008
🇩🇪Berlin, Germany
Investigational Site Number 348005
🇭🇺Sátoraljaújhely, Hungary
Investigational Site Number 356010
🇮🇳Mumbai, India
Investigational Site Number 410010
🇰🇷Gwangju, Korea, Republic of
Investigational Site Number 356004
🇮🇳Mumbai, India
Investigational Site Number 484008
🇲🇽Durango, Mexico
Investigational Site Number 608002
🇵🇭Manila, Philippines
Investigational Site Number 616004
🇵🇱Warszawa, Poland
Investigational Site Number 642008
🇷🇴Ploiesti, Romania
Investigational Site Number 643004
🇷🇺Moscow, Russian Federation
Investigational Site Number 643012
🇷🇺Moscow, 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 710011
🇿🇦Cape Town, South Africa
Investigational Site Number 643008
🇷🇺St-Petersburg, Russian Federation
Investigational Site Number 710009
🇿🇦Cape Town, South Africa
Investigational Site Number 710003
🇿🇦Durban, South Africa
Investigational Site Number 710002
🇿🇦Durban, South Africa
Investigational Site Number 710005
🇿🇦Pretoria, South Africa
Investigational Site Number 710010
🇿🇦Stellenbosch, South Africa
Investigational Site Number 840004
🇺🇸Birmingham, Alabama, United States
Investigational Site Number 840008
🇺🇸San Francisco, California, United States
Investigational Site Number 840048
🇺🇸Miami, Florida, United States
Investigational Site Number 840002
🇺🇸Oklahoma City, Oklahoma, United States
Investigational Site Number 710001
🇿🇦Johannesburg, South Africa
Investigational Site Number 076008
🇧🇷Campinas, Brazil
Investigational Site Number 840022
🇺🇸Dallas, Texas, United States
Investigational Site Number 076001
🇧🇷Curitiba, Brazil
Investigational Site Number 840021
🇺🇸Santa Maria, California, United States
Investigational Site Number 840067
🇺🇸Jupiter, Florida, United States
Investigational Site Number 840016
🇺🇸North Charleston, South Carolina, United States
Investigational Site Number 840025
🇺🇸Jackson, Tennessee, United States
Investigational Site Number 840074
🇺🇸Mesquite, Texas, United States
Investigational Site Number 032006
🇦🇷Caba, Argentina
Investigational Site Number 840069
🇺🇸Lubbock, Texas, United States
Investigational Site Number 840060
🇺🇸Sarasota, Florida, United States
Investigational Site Number 032005
🇦🇷Buenos Aires, Argentina
Investigational Site Number 840041
🇺🇸Jacksonville, Florida, United States
Investigational Site Number 840006
🇺🇸Orlando, Florida, United States
Investigational Site Number 076012
🇧🇷Campinas, Brazil
Investigational Site Number 112001
🇧🇾Minsk, Belarus
Investigational Site Number 056003
🇧🇪Genk, Belgium
Investigational Site Number 056001
🇧🇪Liège, Belgium
Investigational Site Number 076010
🇧🇷Juiz De Fora, Brazil
Investigational Site Number 152008
🇨🇱Santiago, Chile
Investigational Site Number 152013
🇨🇱Santiago, Chile
Investigational Site Number 036005
🇦🇺Clayton, Australia
Investigational Site Number 076003
🇧🇷Sao Paulo, Brazil
Investigational Site Number 036002
🇦🇺East Malvern, Australia
Investigational Site Number 076005
🇧🇷Rio De Janeiro, Brazil
Investigational Site Number 036012
🇦🇺Fitzroy, Australia
Investigational Site Number 152002
🇨🇱Santiago, Chile
Investigational Site Number 840055
🇺🇸Frederick, Maryland, United States
Investigational Site Number 076011
🇧🇷Salvador, Brazil
Investigational Site Number 152011
🇨🇱Santiago, Chile
Investigational Site Number 152014
🇨🇱Talca, Chile
Investigational Site Number 152006
🇨🇱Vina Del Mar, Chile
Investigational Site Number 036009
🇦🇺Herston, Australia
Investigational Site Number 840013
🇺🇸Wheaton, Maryland, United States
Investigational Site Number 840073
🇺🇸Cumberland, Maryland, United States
Investigational Site Number 152004
🇨🇱Valdivia, Chile
Investigational Site Number 170008
🇨🇴Bogota, Colombia
Investigational Site Number 170003
🇨🇴Bogotá, Colombia
Investigational Site Number 170006
🇨🇴Bogotá, Colombia
Investigational Site Number 818001
🇪🇬Cairo, Egypt
Investigational Site Number 840007
🇺🇸Palm Desert, California, United States
Investigational Site Number 036010
🇦🇺Garran, Australia
Investigational Site Number 036006
🇦🇺St Leonards, Australia
Investigational Site Number 036003
🇦🇺Camperdown, Australia
Investigational Site Number 032009
🇦🇷Zarate, Argentina
Investigational Site Number 040001
🇦🇹Graz, Austria
Investigational Site Number 040002
🇦🇹Wien, Austria
Investigational Site Number 840063
🇺🇸Palm Harbor, Florida, United States
Investigational Site Number 840050
🇺🇸Dunedin, Florida, United States
Investigational Site Number 124012
🇨🇦Winnipeg, Canada
Investigational Site Number 152012
🇨🇱Santiago, Chile
Investigational Site Number 840061
🇺🇸Tacoma, Washington, United States
Investigational Site Number 036007
🇦🇺Woodville, Australia
Investigational Site Number 124004
🇨🇦Burlington, Canada
Investigational Site Number 036004
🇦🇺Heidelberg West, Australia
Investigational Site Number 840058
🇺🇸Columbia, South Carolina, United States
Investigational Site Number 032007
🇦🇷Buenos Aires, Argentina
Investigational Site Number 032008
🇦🇷Buenos Aires, Argentina
Investigational Site Number 276003
🇩🇪Frankfurt Am Main, Germany
Investigational Site Number 276007
🇩🇪Berlin, Germany
Investigational Site Number 203001
🇨🇿Praha 2, Czechia
Investigational Site Number 203002
🇨🇿Uherske Hradiste, Czechia
Investigational Site Number 276015
🇩🇪Halle/Saale, Germany
Investigational Site Number 170007
🇨🇴Bucaramanga, Colombia
Investigational Site Number 410014
🇰🇷Anyang, Korea, Republic of
Investigational Site Number 410002
🇰🇷Seoul, Korea, Republic of
Investigational Site Number 276013
🇩🇪Hamburg, Germany
Investigational Site Number 170002
🇨🇴Medellin, Colombia
Investigational Site Number 246001
🇫🇮Helsinki, Finland
Investigational Site Number 410005
🇰🇷Daejeon, Korea, Republic of
Investigational Site Number 554004
🇳🇿Christchurch, New Zealand
Investigational Site Number 554003
🇳🇿Tauranga, New Zealand
Investigational Site Number 246003
🇫🇮Pori, Finland
Investigational Site Number 203004
🇨🇿Hlucin, Czechia
Investigational Site Number 203005
🇨🇿Brno, Czechia
Investigational Site Number 276001
🇩🇪Herne, Germany
Investigational Site Number 276012
🇩🇪Heidelberg, Germany
Investigational Site Number 818002
🇪🇬Cairo, Egypt
Investigational Site Number 276004
🇩🇪Erlangen, Germany
Investigational Site Number 276005
🇩🇪Hamburg, Germany
Investigational Site Number 233001
🇪🇪Tallinn, Estonia
Investigational Site Number 233002
🇪🇪Tallinn, Estonia
Investigational Site Number 246002
🇫🇮Hyvinkää, Finland
Investigational Site Number 300003
🇬🇷Thessaloniki, Greece
Investigational Site Number 348006
🇭🇺Budapest, Hungary
Investigational Site Number 276006
🇩🇪Hildesheim, Germany
Investigational Site Number 348014
🇭🇺Budapest, Hungary
Investigational Site Number 300001
🇬🇷Athens, Greece
Investigational Site Number 348010
🇭🇺Debrecen, Hungary
Investigational Site Number 348011
🇭🇺Eger, Hungary
Investigational Site Number 348013
🇭🇺Gy?r, Hungary
Investigational Site Number 348015
🇭🇺Szombathely, Hungary
Investigational Site Number 348004
🇭🇺Veszprém, Hungary
Investigational Site Number 356015
🇮🇳Ahmedabad, India
Investigational Site Number 356007
🇮🇳Bangalore, India
Investigational Site Number 356003
🇮🇳Chennai, India
Investigational Site Number 356012
🇮🇳Hyderabad, India
Investigational Site Number 356013
🇮🇳Lucknow, India
Investigational Site Number 410004
🇰🇷Daegu, Korea, Republic of
Investigational Site Number 410003
🇰🇷Seoul, Korea, Republic of
Investigational Site Number 410009
🇰🇷Incheon, Korea, Republic of
Investigational Site Number 410013
🇰🇷Daegu, Korea, Republic of
Investigational Site Number 356002
🇮🇳New Delhi, India
Investigational Site Number 410006
🇰🇷Busan, Korea, Republic of
Investigational Site Number 410008
🇰🇷Suwon, Korea, Republic of
Investigational Site Number 410011
🇰🇷Jeonju, Korea, Republic of
Investigational Site Number 440001
🇱🇹Kaunas, Lithuania
Investigational Site Number 410001
🇰🇷Incheon, Korea, Republic of
Investigational Site Number 458001
🇲🇾Ipoh, Malaysia
Investigational Site Number 484001
🇲🇽Mexico, D.F., Mexico
Investigational Site Number 578004
🇳🇴Kristiansand, Norway
Investigational Site Number 554002
🇳🇿Rotorua, New Zealand
Investigational Site Number 554001
🇳🇿Timaru, New Zealand
Investigational Site Number 484004
🇲🇽Merida, Mexico
Investigational Site Number 484007
🇲🇽Metepec, Mexico
Investigational Site Number 484003
🇲🇽Mexico City, Mexico
Investigational Site Number 484005
🇲🇽Monterrey, Mexico
Investigational Site Number 528002
🇳🇱Heerlen, Netherlands
Investigational Site Number 578006
🇳🇴Tønsberg, Norway
Investigational Site Number 608003
🇵🇭Cebu City, Philippines
Investigational Site Number 616006
🇵🇱Torun, Poland
Investigational Site Number 616003
🇵🇱Bialystok, Poland
Investigational Site Number 642002
🇷🇴Bucuresti, Romania
Investigational Site Number 642003
🇷🇴Bucuresti, Romania
Investigational Site Number 642005
🇷🇴Galati, Romania
Investigational Site Number 616012
🇵🇱Wroclaw, Poland
Investigational Site Number 620003
🇵🇹Aveiro, Portugal
Investigational Site Number 620001
🇵🇹Lisboa, Portugal
Investigational Site Number 620002
🇵🇹Lisboa, Portugal
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 643001
🇷🇺Moscow, Russian Federation
Investigational Site Number 643002
🇷🇺Moscow, Russian Federation
Investigational Site Number 643017
🇷🇺Kemerovo, Russian Federation
Investigational Site Number 643006
🇷🇺Kemerovo, Russian Federation
Investigational Site Number 643009
🇷🇺Novosibirsk, Russian Federation
Investigational Site Number 643013
🇷🇺Ufa, Russian Federation
Investigational Site Number 710007
🇿🇦Cape Town, South Africa
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, Turkey
Investigational Site Number 158001
🇨🇳Taipei, Taiwan
Investigational Site Number 710004
🇿🇦Kempton Park, South Africa
Investigational Site Number 724010
🇪🇸Barcelona, Spain
Investigational Site Number 710006
🇿🇦Pretoria, South Africa
Investigational Site Number 158002
🇨🇳Linkou, Taiwan
Investigational Site Number 764001
🇹🇭Bangkok, Thailand
Investigational Site Number 764003
🇹🇭Bangkok, Thailand
Investigational Site Number 804002
🇺🇦Donetsk, Ukraine
Investigational Site Number 804010
🇺🇦Kharkov, Ukraine
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, Spain
Investigational Site Number 804003
🇺🇦Dnipropetrovsk, Ukraine
Investigational Site Number 804008
🇺🇦Kyiv, Ukraine
Investigational Site Number 804004
🇺🇦Kyiv, Ukraine
Investigational Site Number 804009
🇺🇦Zaporizhzhia, Ukraine
Investigational Site Number 840049
🇺🇸Upland, California, United States
Investigational Site Number 710008
🇿🇦Pretoria, South Africa
Investigational Site Number 410007
🇰🇷Seoul, Korea, Republic of
Investigational Site Number 410012
🇰🇷Seoul, Korea, Republic of
Investigational Site Number 643020
🇷🇺Moscow, Russian Federation
Investigational Site Number 840071
🇺🇸Omaha, Nebraska, United States
Investigational Site Number 616001
🇵🇱Krakow, Poland
Investigational Site Number 616005
🇵🇱Lublin, Poland