Clinical trial NCT03120949: Efficacy and Safety of Olokizumab in Subjects With Moderately to Severely Active Rheumatoid Arthritis
Official title: A Multicenter, Open-Label, Phase III Study of the Efficacy and Safety of Olokizumab in Subjects With Moderately to Severely Active Rheumatoid Arthritis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Rheumatoid Arthritis
Keywords: Rheumatoid Arthritis
moderate
severe
subcutaneous
Olokizumab
open-label
Lead sponsor: R-Pharm
Sponsor class: INDUSTRY
Collaborators: name: IQVIA Pvt. Ltd
name: OCT Clinical Trials
First posted: 2017-04-19
Enrollment: 2106
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: The primary objective of this study was to evaluate the long-term safety and tolerability of olokizumab (OKZ) 64 mg administered subcutaneously (SC) once every 2 weeks (q2w) or once every 4 weeks (q4w) in subjects with moderately to severely active rheumatoid arthritis (RA) who previously had completed 24 weeks of double-blind treatment in Study CREDO 1, 2 or 3 (core studies). The long-term efficacy, immunogenicity, the physical function and quality of life of subjects received long-term treatment with OKZ were assessed as well.

Detailed description: This OLE study (CL04041024) included an 82-week open-label Treatment Period that followed completion of one of the core studies (Study CREDO 1, 2 or 3). The OLE open-label Treatment Period lasted from Visit 1 (OLE Baseline/Week 24) to Visit 10 (End of Treatment (EoT)/Week 106), followed by a 20-week Safety Follow-Up Period from Week 106 to Week 126. The first visit of the OLE study was the same visit as the Week 24 visit in the core studies.

Subjects were randomized to 1 of the 2 OKZ treatment groups in the OLE study based on the treatment received in the core studies. Subjects who had received OKZ (q2w or q4w) in the core study in which they had participated (including subjects who received placebo in Study CREDO 3 and were re-randomized to OKZ at Week 16) received the same OKZ treatment regimen in the OLE study. Subjects who had received placebo (Study CREDO 1 and CREDO 2) or adalimumab (Study CREDO 2) in the core study in which they had participated were randomized in a 1:1 ratio to OKZ 64 mg q2w or OKZ 64 mg q4w regimens in the OLE study.

For the first 12 weeks of the OLE, all subjects were required to remain on a stable dose of background methotrexate (MTX) at 15 to 25 mg/week (or≥10 mg/week if there was documented intolerance to higher doses) with a stable route of administration (oral, SC, or intramuscular (IM)). After 12 weeks (Visit 4 \[Week 36\] of the OLE study), the Investigator might adjust the MTX dosage and route, per local guidelines. Methotrexate might be adjusted only for safety reasons according to Investigator discretion before Visit 4 (Week 36) of the OLE study.

Subjects who had been on rescue disease-modifying anti-rheumatic drugs (DMARDs) during the core studies were asked to continue these medications for the first 12 weeks of the OLE study. The Investigator could adjust these background medications if deemed appropriate after Visit 4 (Week 36) of the OLE study. Background rescue therapy might be adjusted only for safety reasons according to Investigator discretion before Visit 4 (Week 36) of the OLE study.

Throughout the study, concomitant treatment with folic acid ≥ 5 mg per week or equivalent was required for all subjects.

Subjects returned to the study site periodically for safety and response assessments as per the Schedule of Events.

The last dose of open-label study treatment in the OLE study was administered at Week 104 for all subjects. After completion of the 82-week open-label Treatment Period, subjects entered the 20-week Safety Follow-Up Period. During the Safety Follow-Up Period, subjects returned for 3 visits at +4, +8, and +22 weeks after the last dose of study treatment.

Subjects who discontinued the open-label treatment prematurely required to come for the EoT Visit 2 weeks after the last study treatment administration and then return for the 3 Safety Follow-Up Visits +4, +8, and +22 weeks after the last study treatment administration.

Adverse events were assessed throughout the study period and evaluated using the Common Technology Criteria version 4.0 (CTCAE v 4.0).

There were ongoing monitoring of safety events, including laboratory findings by the Sponsor or its designee. In addition, safety parameters were assessed throughout the study by an independent Data Safety Monitoring Board (DSMB).

Eligibility criteria: Inclusion Criteria:

Subjects may be enrolled in the study only if they meet all of the following criteria:

1. Subject must be willing and able to sign informed consent
2. Subject must have completed the 24-week double-blind Treatment Period in 1 of the 3 core studies (CL04041022, CL04041023, or CL04041025).
3. Subject must have maintained their stable dose (and route) of MTX 15 to 25 mg/week (or ≥ 10 mg/week if there is documented intolerance to higher doses) during the core study and plan to maintain the same dose and route of administration for ≥ 12 additional weeks
4. Subjects must be willing to take folic acid or equivalent throughout the study.

Exclusion Criteria:

1. Subject with any medically important condition in the core study (e.g., clinically significant laboratory values, frequent Adverse events (AEs) or serious adverse events (SAEs), infection SAEs, and/or other concurrent severe and/or uncontrolled medical condition) which would make this subject unsuitable for inclusion in the open-label extension (OLE) study in the Investigator's judgement.
2. Subject has evidence of active tuberculosis (TB)
3. Subject with a positive or repeated indeterminate interferon-gamma release assay (IGRA) result at Week 22 of the core study

   - Subjects may be enrolled in the OLE study if they fulfill all 3 of the following criteria prior to the first dose of study treatment:
   1. Active TB is ruled out by a certified TB specialist or pulmonologist who is familiar with diagnosing and treating TB (as acceptable per local practice);
   2. The subject starts prophylaxis for latent TB infection (LTBI) according to country-specific/Centers for Disease Control and Prevention (CDC) guidelines (treatment with isoniazid for 6 months is not an appropriate prophylactic regime for this study and it should not be used); and
   3. The subject is willing to complete the entire course of recommended LTBI therapy.
4. Subject has planned surgery during the first 12 weeks of the OLE study
5. Female subjects who are pregnant or who are planning to become pregnant during the study or within 6 months of the last dose of study drug
6. Female subjects of childbearing potential (unless permanent cessation of menstrual periods, determined retrospectively after a woman has experienced 12 months of natural amenorrhea as defined by the amenorrhea with underlying status \[e.g., correlative age\] or 6 months of natural amenorrhea with documented serum follicle-stimulating hormone levels \>40 mIU/mL and estradiol \<20 pg/mL) who are not willing to use a highly effective method of contraception during the study and for at least 6 months after the last administration of study treatment OR Male subjects with partners of childbearing potential not willing to use a highly effective method of contraception during the study and for at least 3 months after the last administration of study treatment.

   Highly effective contraception is defined as:
   * Female sterilization surgery: hysterectomy, surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least 6 weeks prior to the first dose of study treatment in the core study

     * In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by documented follow-up hormone level assessment
   * Total abstinence if it is the preferred and constant lifestyle of the subject. Thus, periodic abstinence such as ovulation, symptothermal, postovulation, calendar methods, and withdrawal are not acceptable methods of contraception.
   * Male sterilization surgery: at least 6 months prior to the first dose of study treatment in the core study (with the appropriate postvasectomy documentation of the absence of sperm in the ejaculate). For female subjects, the vasectomized male should be the only partner.
   * Placement of established intrauterine device (IUD): IUD copper or IUD with progesterone
   * Barrier method (condom and intravaginal spermicide, cervical caps with spermicide, or diaphragm with spermicide) in combination with the following: established oral, injected, or implanted hormone methods of contraception or contraceptive patch.
7. Subject is unwilling or unable to follow the procedures outlined in the protocol.
8. Other medical or psychiatric conditions, or laboratory abnormalities that may increase the potential risk associated with study participation and administration of the study treatment, or that may affect study results interpretation and, as per Investigator's judgement, make the subject ineligible.

Primary outcomes:
measure: Incidence of Treatment-Emergent Adverse Events (AEs), by System Organ Class and Preferred Term (Safety Population)
timeFrame: up to Week 126
measure: Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population)
timeFrame: up to Week 126
measure: Incidence of Treatment-Emergent Adverse Events of Special Interest (AESI)
timeFrame: up to Week 126
measure: Incidence of Treatment-Emergent AEs Leading to Withdrawal of the Study Treatment
timeFrame: up to Week 126
measure: Incidence Rate of Treatment Emergent AEs Per Patient-years of Exposure
timeFrame: up to Week 126
measure: Incidence Rate of Treatment Emergent SAEs Per Patient-years of Exposure
timeFrame: up to Week 126
measure: Incidence Rate of Treatment Emergent AESIs (Safety Population)
timeFrame: up to Week 126
Secondary outcomes:
measure: American College of Rheumatology 20% (ACR20) Response Rates Compare Against Core Baseline Through Week 82
timeFrame: up to Week 82
measure: American College of Rheumatology 50% (ACR50) Response Rates Compare Against Core Baseline Through Week 82
timeFrame: up to Week 82
measure: American College of Rheumatology 70% (ACR70) Response Rates Compare Against Core Baseline Through Week 82
timeFrame: up to Week 82
measure: Proportion of Subjects With Simplified Disease Activity Index (SDAI) Remission Through Week 82
timeFrame: up to week 82
measure: Disease Activity Score 28-joint Count (DAS28) Response Rates Through Week 82
timeFrame: up to Week 82
measure: Change in Health Assessment Questionnaire-Disability Index (HAQ-DI) From Core Baseline at Week 12
timeFrame: Core baseline, Week 12
measure: Change in Health Assessment Questionnaire-Disability Index (HAQ-DI) From Core Baseline at Week 20
timeFrame: Core baseline, Week 20
measure: Change in Health Assessment Questionnaire-Disability Index (HAQ-DI) From Core Baseline at Week 28
timeFrame: Core baseline, Week 28
measure: Change in Health Assessment Questionnaire-Disability Index (HAQ-DI) From Core Baseline at Week 40
timeFrame: Core baseline, Week 40
measure: Change in Health Assessment Questionnaire-Disability Index (HAQ-DI) From Core Baseline at Week 52
timeFrame: Core baseline, Week 52
measure: Change in Health Assessment Questionnaire-Disability Index (HAQ-DI) From Core Baseline at Week 64
timeFrame: Core baseline, Week 64
measure: Change in Health Assessment Questionnaire-Disability Index (HAQ-DI) From Core Baseline at Week 82
timeFrame: Core baseline, Week 82
measure: Proportion of Subjects With Health Assessment Questionnaire - Disability Index (HAQ-DI) Improvement Through Week 82
timeFrame: up to week 82
measure: Changes From Core Baseline Over Time in Clinical Disease Activity Index (CDAI)
timeFrame: up to week 82
Other outcomes:
Locations:
city: Mesa
country: United States
facility: AZ Arthritis & Rheum' Research
state: Arizona
city: Phoenix
country: United States
facility: Arizona Arthritis & Rheumatology Associates, P.C.
state: Arizona
city: Sun City
country: United States
facility: Arizona Arthritis & Rheumatology Research, PLLC
state: Arizona
city: Hot Springs
country: United States
facility: CHI St. Vincent Hot Springs
state: Arkansas
city: Covina
country: United States
facility: Medvin Clinical Research
state: California
city: Hemet
country: United States
facility: C.V Mehta MD Med Corp..
state: California
city: La Palma
country: United States
facility: Advanced Medical Research, LLC
state: California
city: Los Alamitos
country: United States
facility: Valerius Medical Group
state: California
city: Palo Alto
country: United States
facility: Stanford University School of Medicine
state: California
city: San Diego
country: United States
facility: Rheumatology Center of San Diego
state: California
city: San Leandro
country: United States
facility: East Bay Rheumatology Medical Group, Inc.
state: California
city: Upland
country: United States
facility: Inland Rheumatology Clinical Trials, Inc.
state: California
city: West Hills
country: United States
facility: Center for Rheumatology Research, Comprehensive Rheumatology Center
state: California
city: Whittier
country: United States
facility: Medvin Clinical Research
state: California
city: Denver
country: United States
facility: Denver Arthritis Clinic
state: Colorado
city: Bridgeport
country: United States
facility: New England Research Associates LLC
state: Connecticut
city: Newark
country: United States
facility: Javed Rheumatology Associates
state: Delaware
city: Boca Raton
country: United States
facility: RASF - Clinical Research Center
state: Florida
city: Hialeah
country: United States
facility: Reliable Clinical Research, LLC
state: Florida
city: Miami
country: United States
facility: Pharmax Research Clinic
state: Florida
city: Miami
country: United States
facility: Medical Research Center of Miami
state: Florida
city: Miami
country: United States
facility: Suncoast Research Group, LLC
state: Florida
city: Orlando
country: United States
facility: Omega Research Consultants
state: Florida
city: Palm Harbor
country: United States
facility: Arthritis Research of Florida, INC
state: Florida
city: Pembroke Pines
country: United States
facility: Family Clinical Trials, LLC.
state: Florida
city: Tampa
country: United States
facility: AdventHealth Medical Group, PA
state: Florida
city: Venice
country: United States
facility: Lovelace Scientific Resources, Inc.
state: Florida
city: Gainesville
country: United States
facility: Arthritis Center of North Georgia
state: Georgia
city: Marietta
country: United States
facility: Marietta Rheumatology Associates, PC
state: Georgia
city: Idaho Falls
country: United States
facility: Institute of Arthritis Research
state: Idaho
city: Kansas City
country: United States
facility: University of Kansas Hospital
state: Kansas
city: Bowling Green
country: United States
facility: Graves Gilbert Clinic
state: Kentucky
city: Monroe
country: United States
facility: The Arthritis & Diabetes Clinic, Inc.
state: Louisiana
city: Hagerstown
country: United States
facility: Klein and Associates, M.D., P.A.
state: Maryland
city: Wheaton
country: United States
facility: The Center for Rheumatology and Bone Research
state: Maryland
city: Worcester
country: United States
facility: Clinical Pharmacology Study Group
state: Massachusetts
city: Grand Blanc
country: United States
facility: AA MRC LLC Ahmed Arif Medical Research Center
state: Michigan
city: Tupelo
country: United States
facility: North MS Medical Clinics, Inc.
state: Mississippi
city: Kalispell
country: United States
facility: Glacier View Research Institute-Rheumatology
state: Montana
city: Lincoln
country: United States
facility: Physician Research Collaboration
state: Nebraska
city: Freehold
country: United States
facility: Arthritis & Osteoporosis Associates, PA
state: New Jersey
city: Albuquerque
country: United States
facility: Lovelace Scientific Resources, Inc.
state: New Mexico
city: Brooklyn
country: United States
facility: NYU Langone ambulatory care
state: New York
city: Greensboro
country: United States
facility: Medication Management, LLC
state: North Carolina
city: Leland
country: United States
facility: Cape Fear Arthritis Care
state: North Carolina
city: Wilmington
country: United States
facility: Carolina Arthritis Associates
state: North Carolina
city: Minot
country: United States
facility: Trinity Medical Group
state: North Dakota
city: Cincinnati
country: United States
facility: Cincinnati Rheumatic Disease Study Group
state: Ohio
city: Dayton
country: United States
facility: STAT Research, Inc.
state: Ohio
city: Toledo
country: United States
facility: Clinical Research Source, Inc.
state: Ohio
city: Oklahoma City
country: United States
facility: Health Research of Oklahoma, PLLC
state: Oklahoma
city: Oklahoma City
country: United States
facility: Lynn Health Science Institute
state: Oklahoma
city: Duncansville
country: United States
facility: Altoona Center for Clinical Research, P.C.
state: Pennsylvania
city: Philadelphia
country: United States
facility: Arthritis Group
state: Pennsylvania
city: Summerville
country: United States
facility: Low Country Rheumatology, PA
state: South Carolina
city: Amarillo
country: United States
facility: Amarillo Center for Clinical Research
state: Texas
city: Austin
country: United States
facility: Austin Regional Clinic, P.A.
state: Texas
city: Baytown
country: United States
facility: Accurate Clinical Management., LLC
state: Texas
city: Colleyville
country: United States
facility: Precision Comprehensive Clinical Research Solutions
state: Texas
city: Cypress
country: United States
facility: Pioneer Research Solutions, Inc.
state: Texas
city: Houston
country: United States
facility: Therapeutic Concepts Rheumatology,LLC
state: Texas
city: Houston
country: United States
facility: Rheumatology Clinic of Houston, P.A.
state: Texas
city: Houston
country: United States
facility: Houston Institute For Clinical Research
state: Texas
city: Houston
country: United States
facility: Accurate Clinical Mangemnt - Partner
state: Texas
city: Houston
country: United States
facility: Accurate Clinical Research, Inc.
state: Texas
city: League City
country: United States
facility: Accurate Clinical Research, Inc.
state: Texas
city: Lubbock
country: United States
facility: West Texas Clinical Research
state: Texas
city: San Antonio
country: United States
facility: Dr Alex De Jesus Rheumatology, P.A.
state: Texas
city: The Woodlands
country: United States
facility: Advanced Rheumatology of Houston
state: Texas
city: Tomball
country: United States
facility: DM Clinical Research
state: Texas
city: Spokane
country: United States
facility: Arthritis Northwest, PLLC
state: Washington
city: Mar del Plata
country: Argentina
facility: Centro de Investigaciones Medicas Mar del Plata
state: Buenos Aires
city: Quilmes
country: Argentina
facility: Instituto Medico CER
state: Buenos Aires
city: Quilmes
country: Argentina
facility: Instituto de Investigaciones Clinicas Quilmes
state: Buenos Aires
city: Venado Tuerto
country: Argentina
facility: Sanatorio San Martin
state: Santa Fe
city: San Miguel de Tucuman
country: Argentina
facility: Centro Medico Privado de Reumatologia
state: Tucuman
city: Buenos Aires
country: Argentina
facility: Instituto de Investigaciones Clinicas-Mar del Plata
city: Ciudad Autonoma Buenos Aires
country: Argentina
facility: Organizacion Medica de Investigacion (OMI)
city: Ciudad Autonoma Buenos aires
country: Argentina
facility: APRILLUS Asistencia e Investigacion
city: Ciudad Autonoma Buenos Aires
country: Argentina
facility: Instituto Centenario
city: Cordoba
country: Argentina
facility: Hospital Privado Centro Medico de Cordoba
city: Córdoba
country: Argentina
facility: Instituto DAMIC Fundacion Rusculleda
city: San Juan
country: Argentina
facility: CER San Juan Centro Polivalente de Asistencia e Inv. Clinica
city: Santa Fe
country: Argentina
facility: Clinica de Higado y Aparato Digestivo
city: Tucuman
country: Argentina
facility: Centro de Investigaciones Reumatológicas
city: Minsk
country: Belarus
facility: Minsk City Clinical Hospital #1
state: Minsk Oblast
city: Vitebsk
country: Belarus
facility: Vitebsk Clinical Hospital
state: Vitebsk Oblast
city: Fortaleza
country: Brazil
facility: HUWC - UFC - Hospital Universitário Walter Cantídio - Universidade Federal do Ceará
state: Ceará
city: Vitória
country: Brazil
facility: CEDOES - Diagnóstico e Pesquisa
state: Espírito Santo
city: Goiânia
country: Brazil
facility: CIP - Centro Internacional de Pesquisa
state: Goiás
city: Juiz de Fora
country: Brazil
facility: CMiP - Centro Mineiro de Pesquisa
state: Minas Gerais
city: Curitiba
country: Brazil
facility: CETI - Centro de Estudos em Terapias Inovadoras Ltda.
state: Paraná
city: Maringá
country: Brazil
facility: Clinilive - Clínica do Idoso e Pesquisa Clínica
state: Paraná
city: Lajeado
country: Brazil
facility: Hospital Bruno Born
state: Rio Grande Do Sul
city: Pôrto Alegre
country: Brazil
facility: LMK Serviços Médicos S/S Ltda
state: Rio Grande Do Sul
city: Itajaí
country: Brazil
facility: Clínica de Neoplasias Litoral Ltda.
state: Santa Catarina
city: Santo André
country: Brazil
facility: Faculdade de Medicina do ABC
state: Sao Paulo
city: Sao Bernardo Do Campo
country: Brazil
facility: Centro Multidisciplinar de Estudos Clínicos - CEMEC
state: Sao Paulo
city: Rio de Janeiro
country: Brazil
facility: CCBR Brasil Centro de Pesquisas e Análises Clínicas Ltda.
city: São Paulo
country: Brazil
facility: CPCLIN - Centro de Pesquisas Clínicas Ltda.
city: São Paulo
country: Brazil
facility: Associação de Assistência à Criança Deficiente - AACD
city: Pleven
country: Bulgaria
facility: DCC 'Sv. Pantaleymon' OOD
city: Plovdiv
country: Bulgaria
facility: UMHAT Pulmed OOD
city: Plovdiv
country: Bulgaria
facility: UMHAT "Kaspela", EOOD
city: Ruse
country: Bulgaria
facility: MHAT - Ruse, AD
city: Sevlievo
country: Bulgaria
facility: Medizinski Zentar-1-Sevlievo EOOD
city: Shumen
country: Bulgaria
facility: MHAT - Shumen, AD
city: Sofia
country: Bulgaria
facility: NMTH "Tsar Boris III"
city: Sofia
country: Bulgaria
facility: MHAT "Lyulin", EAD
city: Sofia
country: Bulgaria
facility: Medical Center "Excelsior", OOD
city: Sofia
country: Bulgaria
facility: UMHAT "Sv. Ivan Rilski", EAD
city: Sofia
country: Bulgaria
facility: MC "Synexus - Sofia", EOOD
city: Veliko Tarnovo
country: Bulgaria
facility: MDHAT 'Dr. Stefan Cherkezov', AD
city: Barranquilla
country: Colombia
facility: Centro de Reumatologia y Ortopedia SAS
city: Bogotá
country: Colombia
facility: Centro de Investigacion en Reumatologia y Especialidades Medicas SAS. CIREEM
city: Bogotá
country: Colombia
facility: Fundacion Instituto de Reumatologia Fernando Chalem
city: Bucaramanga
country: Colombia
facility: Medicity S.A.S.
city: Cali
country: Colombia
facility: Clinica de Artritis Temprana S.A.S
city: Brno
country: Czechia
facility: CCR Brno s.r.o
city: Brno
country: Czechia
facility: IMEDICA s.r.o.
city: Brno
country: Czechia
facility: Revmatologie s.r.o.
city: Jihlava
country: Czechia
facility: Nemocnice Jihlava p.o.
city: Kladno
country: Czechia
facility: MUDr Gabriela Simkova Ordinace Lekare Specialisty Interna Revmatologie
city: Olomouc
country: Czechia
facility: CTCenter MaVe s.r.o.
city: Ostrava - Trebovice
country: Czechia
facility: ARTROSCAN s.r.o.
city: Ostrava
country: Czechia
facility: Vesalion s.r.o.
city: Pardubice
country: Czechia
facility: ARTHROHELP s.r.o.
city: Pardubice
country: Czechia
facility: CCR Czech, a.s.
city: Praha 2
country: Czechia
facility: Revmatologicky ustav
city: Praha 3
country: Czechia
facility: CCR Prague s.r.o.
city: Praha 4 Nusle
country: Czechia
facility: MUDR Zuzana URBANOVA Revmatologie
city: Praha 4
country: Czechia
facility: MUDR Zuzana URBANOVA Revmatologie
city: Praha 5
country: Czechia
facility: Fakultni nemocnice v Motole
city: Praha
country: Czechia
facility: CLINTRIAL s.r.o.
city: Praha
country: Czechia
facility: Affidea Praha s.r.o.
city: Uherske Hradiste
country: Czechia
facility: Medical Plus s.r.o.
city: Zlin
country: Czechia
facility: PV - MEDICAL, s.r.o.
city: Tallinn
country: Estonia
facility: East Tallinn Central Hospital
city: Tartu
country: Estonia
facility: Meditrials OU
city: Bad Nauheim
country: Germany
facility: Kerckhoff-Klinik gGmbH
state: Hessen
city: Aachen
country: Germany
facility: Rheumapraxis Dr. med. Reiner Kurthen
state: Nordrhein Westfalen
city: Ratingen
country: Germany
facility: Studienambulanz Dr. Wassenberg
state: Nordrhein Westfalen
city: Magdeburg
country: Germany
facility: SMO.MD GmbH
state: Sachsen Anhalt
city: Berlin
country: Germany
facility: Klinische Forschung Berlin-Mitte GmbH
city: Hamburg
country: Germany
facility: HRF Hamburger Rheuma Forschungszentrum
city: Baja
country: Hungary
facility: Principal SMO Kft.
city: Balatonfüred
country: Hungary
facility: DRC Gyogyszervizsgalo Kozpont Kft.
city: Budapest
country: Hungary
facility: Clinexpert Kft.
city: Budapest
country: Hungary
facility: Obudai Egeszsegugyi Centrum Kft.
city: Kiskunhalas
country: Hungary
facility: Kiskunhalasi Semmelweis Korhaz
city: Szolnok
country: Hungary
facility: MAV Korhaz es Rendelointezet
city: Székesfehérvár
country: Hungary
facility: DRC Szekesfehervar
city: Veszprem
country: Hungary
facility: Vital-Medicina Kft.
city: Anyang-si
country: Korea, Republic of
facility: Hallym University Sacred Heart Hospital
state: Gyeonggi-do
city: Suwon-si
country: Korea, Republic of
facility: Ajou University Hospital
state: Gyeonggi-do
city: Daejeon
country: Korea, Republic of
facility: Eulji University Hospital
city: Gwangju
country: Korea, Republic of
facility: Chonnam National University Hospital
city: Jeju
country: Korea, Republic of
facility: Jeju National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University No. 31 Office, Pediatric Oncology Clinic
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea, Seoul St. Mary's Hospital
city: Liepaja
country: Latvia
facility: Dr.Saulite-Kandevica Private Practice
city: Alytus
country: Lithuania
facility: Alytus Regional S. Kudirkos Hospital, Public Institution
city: Kaunas
country: Lithuania
facility: Republican Kaunas Hospital, Public Institution
city: Klaipeda
country: Lithuania
facility: Klaipeda University Hospital, Public Institution
city: Siauliai
country: Lithuania
facility: Siauliai Republican Hospital, Public Institution
city: Vilnius
country: Lithuania
facility: Center Outpatient Clinic, Public Institution
city: Vilnius
country: Lithuania
facility: Vilnius University Hospital Santariskiu Clinics, Public Institution
city: Mexico
country: Mexico
facility: Clinicos Asociados BOCM S.C.
state: Distrito Federal
city: Mexico
country: Mexico
facility: Centro de Investigacion Clínica GRAMEL S.C
state: Distrito Federal
city: Mexico
country: Mexico
facility: Comite Mexicano Para la Prevencion de Osteoporosis AC
state: Distrito Federal
city: Mexico
country: Mexico
facility: Clinstile, S.A. de C.V.
state: Distrito Federal
city: Guadalajara
country: Mexico
facility: Clinica de Investigacion en Reumatologia y Obesidad S.C.
state: Jalisco
city: Guadalajara
country: Mexico
facility: Centro de Estudios de Investigacion Basica y Clinica SC
state: Jalisco
city: Monterrey
country: Mexico
facility: Accelerium S. de R.L. de C.V.
state: Nuevo León
city: Monterrey
country: Mexico
facility: Universidad Autonoma de Nuevo Leon, Hospital Universitario Dr. Jose Eleuterio Gonzalez
state: Nuevo León
city: Chihuahua
country: Mexico
facility: Investigacion y Biomedicina de Chihuahua, S.C.
city: Mexico City
country: Mexico
facility: Clinical Research Institute S.C.
city: San Luis Potosí
country: Mexico
facility: Centro de Alta Especialidad en Reumatología e Investigación del Potosí, S.C.
city: Bialystok
country: Poland
facility: CERMED
city: Bialystok
country: Poland
facility: ZDROWIE Osteo-Medic
city: Bydgoszcz
country: Poland
facility: Szpital Uniwersytecki nr 2 im.dr J. Biziela
city: Grodzisk Mazowiecki
country: Poland
facility: MCBK Iwona Czajkowska Anna Podrażka- Szczepaniak S.C.
city: Kielce
country: Poland
facility: Polimedica Centrum Badań, Profilaktyki I Leczenia
city: Lodz
country: Poland
facility: CCBR - Lodz - PL
city: Lodz
country: Poland
facility: Centrum Medyczne AMED
city: Olsztyn
country: Poland
facility: ETYKA Osrodek Badan Klinicznych
city: Sieradz
country: Poland
facility: Szpital Wojewodzki im. Prymasa Kardynala Stefana Wyszynskiego
city: Skierniewice
country: Poland
facility: Clinmed Research
city: Sochaczew
country: Poland
facility: RCMed
city: Staszow
country: Poland
facility: KO-MED Centra Kliniczne Staszow
city: Tomaszow Lubelski
country: Poland
facility: Samodzielny Publiczny ZOZ Tomaszow Lubelski
city: Torun
country: Poland
facility: Nasz lekarz Przychodnie Medyczne
city: Warszawa
country: Poland
facility: Medycyna Kliniczna
city: Warszawa
country: Poland
facility: Rheuma Medicus Zaklad Opieki Zdrowotnej
city: Warszawa
country: Poland
facility: McM Polimedica
city: Zamosc
country: Poland
facility: KO-MED Centra Kliniczne Zamosc
city: Zgierz
country: Poland
facility: Santa Familia Centrum Badan, Profilaktyki i Leczenia
city: Barnaul
country: Russian Federation
facility: FSBEI HE "Altai State Medical University of the Ministry of Healthcare of Russian Federation"
state: Altai Region
city: Kemerovo
country: Russian Federation
facility: Medical Center LLC "Maksimum Zdoroviya"
state: Kemerovo Oblast
city: Kemerovo
country: Russian Federation
facility: SAHI of Kemerovo region "Regional Clinical Hospital for War Veterans"
state: Kemerovskaya Oblast
city: Kursk
country: Russian Federation
facility: Budgetary Healthcare Institution "Kursk Regional Clinical Hospital" of Healthcare Committee of Kursk region
state: Kurskaya Oblast
city: Saint Petersburg
country: Russian Federation
facility: SPb SBHI "Clinical Rheumatological Hospital #25", Fourth Rheumatology Unit
state: Leningradskaya Oblast
city: Moscow
country: Russian Federation
facility: SBHI of Moscow "City Clinical Hospital No.1 n.a. Pirogov" Healthcare Department of Moscow
state: Moscovskaya Oblast
city: Moscow
country: Russian Federation
facility: FSAEI HE "First MSMU n.a. I.M. Sechenov of the Ministry of Health of the Russian Federation" University Clinical Hospital No.1
state: Moscovskaya Oblast
city: Moscow
country: Russian Federation
facility: FSAEI HE "First MSMU n.a. I.M. Sechenov of the Ministry of Health of the Russian Federation"
state: Moscovskaya Oblast
city: Moscow
country: Russian Federation
facility: State Budgetary Healthcare Institution "City Clinical Hospital # 15 n.a O.M. Filatov" of Moscow Healtheare Department
state: Moscow Region
city: Moscow
country: Russian Federation
facility: SBHI of Moscow "City Clinical Hospital #4 of Moscow Healthcare Departament"
state: Moskovskaya Oblast
city: Nizhniy Novgorod
country: Russian Federation
facility: SBHI of Nizhny Novgorod Region "Nizhny Novgorod Regional Clinical Hospital n.a.Semashko"
state: Nizhegorodskaya Oblast
city: Nizhny Novgorod
country: Russian Federation
facility: SBHI of Nizhegorodsky Region "State Clinical Hospital #5 of Nizhegorodsky District of Nizhny Novgorod"
state: Nizhny Novgorod Oblast
city: Novosibirsk
country: Russian Federation
facility: State Autonomous Healthcare Institution of Novosibirsk region "City Polyclinic #1"
state: Novosibirsk Oblast
city: Omsk
country: Russian Federation
facility: LLC "Clinical Diagnostic Center "Ultramed"
state: Omskaya Oblast
city: Omsk
country: Russian Federation
facility: Budgetary Healthcare Institution of Omsk Region "Regional Clinical Hospital"
state: Omskaya Oblast
city: Petrozavodsk
country: Russian Federation
facility: SBHI of the Republic of Karelia "Republican Hospital named after V.A. Baranov"
state: Republic Of Karelia
city: Ufa
country: Russian Federation
facility: State Budgetary Healthcare Institution "Republican Clinical Hospital n.a. G.G. Kuvatov"
state: Respublic Of Bashkortostan
city: Rostov
country: Russian Federation
facility: FSBEI HE "Rostov State Medical Unversity" of Ministry of Health of the Russian Federation
state: Rostovskaya Oblast
city: Ryazan
country: Russian Federation
facility: FSBEI HE 'Ryazan State Medical University n.a. I.P.Pavlov" of the Ministry of Health of Russian Federation
state: Ryazan Oblast
city: Saratov
country: Russian Federation
facility: FSBEI HE "Saratov SMU n.a. V.I.Razumovsky of Ministry of Health of Russian Federation"
state: Saratovskaya Oblast
city: Saratov
country: Russian Federation
facility: State Healthcare Institution "Regional Clinical Hospital"
state: Saratovskaya Oblast
city: Smolensk
country: Russian Federation
facility: Private Healthcare Institution "Clinical Hospital Russian Railways-Medicine of City Smolensk"
state: Smolenskaya Oblast
city: Stavropol'
country: Russian Federation
facility: FSBEI HE StSMU MOH Russia based on SBHI of Stavropol Region "Stavropol Regional Clinical Hospital"
state: Stavropol Region
city: Ekaterinburg
country: Russian Federation
facility: State Autonomous Healthcare Institution of Sverdlovsk Region "Sverdlovsk Regional Clinical Hospital No.1"
state: Sverdlovskaya Oblast
city: Ekaterinburg
country: Russian Federation
facility: FSBEI HE "Ural State Medical University" of Ministry of Health of Russian Federation based on MBI "Central City Clinical Hospital No.6"
state: Sverdlovskaya Oblast
city: Kazan'
country: Russian Federation
facility: FSBEI HE "Kazan State Medical University of the Ministry of Health of the Russian Federation" on the base of SAHI "Republican Clinical Hospital of the Ministry of Health of Tatarstan Republic"
state: The Republic Of Tatarstan
city: Tula
country: Russian Federation
facility: State Healthcare Institution of Tula region "Tula Regional Clinical Hospital"
state: Tulskaya Oblast
city: Ulyanovsk
country: Russian Federation
facility: State Healthcare Institution "Ulyanovsk Regional Clinical Hospital"
state: Ulyanovskaya Oblast
city: Vladimir
country: Russian Federation
facility: SBHI of Vladimir Region "Regional Clinical Hospital", Rheumatology Departament
state: Vladimirskaya Oblast
city: Yaroslavl
country: Russian Federation
facility: State Autonomous Helthcare Institution of Yaroslavl region "Clinical Hospital of Emergency Care n.a. Solovyev"
state: Yaroslavsakaya Oblast
city: Yaroslavl'
country: Russian Federation
facility: SBHI "Yaroslavl Regional Clinical Hospital", Rheumatology department
state: Yaroslavskaya Oblast
city: Moscow
country: Russian Federation
facility: FSBSI "Scientific Research Institute of Rheumatology n.a. V.A. Nasonova"
city: Moscow
country: Russian Federation
facility: FSAEI HE "First MSMU n.a. I.M. Sechenov of the Ministry of Health of the Russian Federation"
city: Saint Petersburg
country: Russian Federation
facility: FSBI "National Medical Research Center n.a. V.A.Almazov" of the Ministry of Healthcare of the Russian Federation
city: Tainan
country: Taiwan
facility: Chi Mei Medical Center, Yung Kang Branch
city: Taoyuan
country: Taiwan
facility: Chang Gung Memorial Hospital, Linkou
city: Torquay
country: United Kingdom
facility: Torbay Hospital
state: Devon
city: London
country: United Kingdom
facility: Whipps Cross University Hospital
state: Greater London
city: London
country: United Kingdom
facility: Royal Free Hospital
state: Greater London
city: Basingstoke
country: United Kingdom
facility: Basingstoke and North Hampshire Hospital
state: Hampshire
city: Maidstone
country: United Kingdom
facility: Maidstone Hospital
state: Kent
city: Wirral
country: United Kingdom
facility: Arrowe Park Hospital
state: Merseyside
Study officials:
affiliation: Chief Medical Officer, R-Pharm
name: Mikhail Samsonov
role: STUDY_DIRECTOR
References: