Clinical trial NCT02760407: Evaluation of the Efficacy and Safety of Two Dosing Regimens of Olokizumab (OKZ), Compared to Placebo and Adalimumab, in Subjects With Rheumatoid Arthritis (RA) Who Are Taking Methotrexate But Have Active Disease
Official title: A Randomized, Double-Blind, Parallel-Group, Placebo- and Active-Controlled, Multicenter Phase III Study of the Efficacy and Safety of Olokizumab in Subjects With Moderately to Severely Active Rheumatoid Arthritis Inadequately Controlled by Methotrexate Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Rheumatoid Arthritis
Keywords: moderate Rheumatoid Arthritis
severe Rheumatoid Arthritis
subcutaneous
Olokizumab
Lead sponsor: R-Pharm
Sponsor class: INDUSTRY
Collaborators: name: Quintiles, Inc.
name: OCT Clinical Trials
First posted: 2016-05-03
Enrollment: 1648
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 purpose of this study was to determine how effective and safe the study drug Olokizumab was in patients with Rheumatoid Arthritis (RA) who had been already receiving but not fully responding to treatment with methotrexate (MTX).

The primary objective of this study was to evaluate the efficacy of OKZ 64 mg administered subcutaneously (SC) once every 2 weeks (q2w) or once every 4 weeks (q4w) relative to placebo in subjects with moderately to severely active RA inadequately controlled by MTX therapy.

The secondary objective was to evaluate the efficacy of OKZ relative to adalimumab in subjects with moderately to severely active RA inadequately controlled by MTX therapy.

Detailed description: The goal of this Phase III study was to assess the efficacy, safety and tolerability of OKZ in subjects with moderately to severely active RA who had responded inadequately to MTX. The primary endpoint of the trial was at Week 12. Olokizumab was expected to reduce the disease activity and improve physical function. The study was expected to provide safety information in a large group of subjects over at least a 24 week period.

This study included a 4-week Screening Period, a double-blind Treatment Period from Week 0 to Week 24, and a Safety Follow-Up Period from Week 24 to Week 44. Subjects were assessed for eligibility to enter the study during the 4-week Screening Period. A total of 1575 subjects were planned to be randomly assigned to 1 of 4 treatment groups in a 2:2:2:1 ratio (450, 450, 450, and 225 subjects per group, respectively):

1. Olokizumab 64 mg q4w: SC injection of OKZ 64 mg q4w (alternating with SC injection of placebo q4w to maintain blinding) + MTX
2. Olokizumab 64 mg q2w: SC injection of OKZ 64 mg q2w + MTX
3. Adalimumab 40 mg q2w: SC injection of adalimumab 40 mg q2w + MTX
4. Placebo: SC injection of placebo q2w + MTX

Throughout the double-blind Treatment Period, all subjects were required to remain on a stable dose of background MTX with a stable route of administration. Concomitant treatment with folic acid was required for all subjects. The last dose of study treatment (OKZ, adalimumab, or placebo) was at Week 22 in all groups.

Following Visit 2 (randomization; Week 0), subjects returned to the study site at least every 2 weeks through Week 24 for response and safety assessments.

At Week 14, subjects who had not improved by at least 20% in both swollen and tender joint counts were classified as nonresponders and were administered sulfasalazine and/or hydroxychloroquine as rescue medication in addition to the assigned treatment.

After completion of the 24-week double-blind Treatment Period, subjects either rolled over into the long-term open-label extension (OLE) study or entered the Safety Follow-Up Period. During the Safety Follow-Up Period, subjects returned for visits +4, +8, and +22 weeks after the last dose of study treatment.

Subjects who had discontinued randomized treatment prematurely were required to come for the End of Treatment (EoT) Visit 2 weeks after the last study treatment administration and then continue with the scheduled study visits.

Adverse events (AEs) were assessed throughout the study (starting when the subject signed the informed consent form) and evaluated using the Common Terminology Criteria for Adverse Events Version 4.0. There was ongoing monitoring of safety events, including laboratory findings, by the Sponsor or the Sponsor's designee. In addition, safety was assessed throughout the study by an independent Data Safety Monitoring Board and potential major adverse cardiac events were evaluated by an independent Cardiovascular Adjudication Committee.

The study was conducted at 208 sites across 18 countries globally (in US, European Union (EU),United Kingdom (UK), Russian Federation, Asia, Latin America).

Eligibility criteria: Inclusion Criteria:

* Subjects willing and able to sign informed consent
* Subjects must have a diagnosis of adult onset RA classified by ACR/EULAR 2010 revised classification criteria for RA for at least 12 weeks prior to Screening. (If the subject was diagnosed according to ACR 1987 criteria previously, the Investigator may classify the subject per ACR 2010 retrospectively, using available source data)
* Inadequate response to treatment with oral, SC, or intramuscular MTX (defined as a subject with at least 12 weeks of exposure prior to Screening and with either absence of any documented clinically significant response, or documented initial clinical response with subsequent loss of that response or partial response) for at least 12 weeks prior to Screening at a dose of 15 to 25 mg/week (or ≥10 mg/week if intolerant to higher doses). The dose and route of administering MTX had to have been stable for at least 6 weeks prior to Screening. A lower dose of MTX (≥7.5 mg/week) was permitted for subjects enrolled in the Republic of Korea, consistent with local clinical practice.
* Subjects must be willing to take folic acid or equivalent throughout the study.
* Subjects must have moderately to severely active RA disease as defined by all of the following:

  * ≥6 tender joints (68 joint count) at Screening and baseline; and
  * ≥6 swollen joints (66 joint count) at Screening and baseline; and
  * CRP above the normal range (ULN) at Screening based on the central laboratory results.

Exclusion Criteria:

* Diagnosis of any other inflammatory arthritis or systemic rheumatic disease (eg, gout, psoriatic or reactive arthritis, Crohn's disease, Lyme disease, juvenile idiopathic arthritis, or systemic lupus erythematosus). However, subjects could have secondary Sjogren's syndrome or hypothyroidism.
* Subjects who are Steinbrocker class IV functional capacity (incapacitated, largely or wholly bed-ridden or confined to a wheelchair, with little or no self-care)
* Prior exposure to any licensed or investigational compound directly or indirectly targeting IL 6 or IL 6R (including tofacitinib or other Janus kinases and spleen tyrosine kinase \[SYK\] inhibitors)
* Prior treatment with cell depleting therapies including anti CD20 or investigational agents (e.g., CAMPATH, anti CD4, anti CD5, anti CD3, and anti CD19)
* Prior use of bDMARDs
* Use of parenteral and/or intra-articular glucocorticoids within 4 weeks prior to baseline
* Use of oral glucocorticoids greater than 10 mg/day prednisone (or equivalent) or change in dosage within 2 weeks prior to baseline
* Prior documented history of no response to hydroxychloroquine and sulfasalazine
* Prior use of cDMARDs (other than MTX) within the following windows prior to baseline (cDMARDs should not be discontinued to facilitate a subject's participation in the study, but should instead have been previously discontinued as part of a subject's medical management of RA):

  1. 4 weeks for sulfasalazine, azathioprine, cyclosporine, hydroxychloroquine, chloroquine, gold, penicillamine, minocycline, or doxycycline
  2. 12 weeks for leflunomide unless the subject has completed the following elimination procedure at least 4 weeks prior to baseline: Cholestyramine at a dosage of 8 grams 3 times daily for at least 24 hours, or activated charcoal at a dosage of 50 grams 4 times daily for at least 24 hours
  3. 24 weeks for cyclophosphamide
* Vaccination with live vaccines in the 6 weeks prior to baseline or planned vaccination with live vaccines during the study
* Participation in any other investigational drug study within 30 days or 5 times the terminal half-life of the investigational drug, whichever is longer, prior to baseline
* Other treatments for RA (e.g., Prosorba Device/Column) within 6 months prior to baseline
* Use of intra-articular hyaluronic acid injections within 4 weeks prior to baseline
* Use of non-steroidal anti-inflammatory drugs (NSAIDs) on unstable dose or switching of NSAIDs within 2 weeks prior to baseline
* Previous participation in this study (randomized) or another study of OKZ
* Subjects with concurrent acute or chronic viral hepatitis B or C infection as detected by blood tests at Screening(e.g., positive for hepatitis B surface antigen \[HBsAg\], total hepatitis B core antibody \[anti-HBc\], or hepatitis C virus antibody \[HCV Ab\]). Subjects who are are positive for hepatitis B surface antibodies (anti-HBs), but negative for HBsAg and anti-HBc, will be eligible
* Subjects with human immunodeficiency virus (HIV) infection
* Subjects with:

  1. Suspected or confirmed current active TB disease or a history of active TB disease
  2. Close contact (i.e., sharing the same household or other enclosed environment, such as a social gathering place, workplace, or facility, for extended periods during the day) with an individual with active TB within 1.5 years prior to Screening
* Concurrent malignancy or a history of malignancy within the last 5 years (with the exception of successfully treated carcinoma of the cervix in situ and successfully treated basal cell carcinoma and squamous cell carcinoma not less than 1 year prior to Screening \[and no more than 3 excised skin cancers within the last 5 years prior to Screening\])
* Subjects with any infection requiring oral antibiotic or antiviral therapy in the 2 weeks prior to Screening or at baseline, injectable anti-infective therapy in the last 4 weeks prior to baseline, or serious or recurrent infection with history of hospitalization in the 6 months prior to baseline
* Subjects with evidence of disseminated herpes zoster infection, zoster encephalitis, meningitis, or other non-self-limited herpes zoster infections in the 6 months prior to baseline
* Subjects with planned surgery during the study or surgery ≤ 4 weeks prior to Screening and from which the subject has not fully recovered, as judged by the Investigator
* Subjects with diverticulitis or other symptomatic GI conditions that might predispose the subject to perforations, including subjects with history of such predisposing conditions (e.g., diverticulitis, GI perforation, or ulcerative colitis)
* Pre-existing central nervous system demyelinating disorders (e.g., multiple sclerosis and optic neuritis)
* History of chronic alcohol or drug abuse as judged by the Investigator
* Female subjects who are pregnant, currently lactating, have lactated within the last 12 weeks, or who are planning to become pregnant during the study or within 6 months of last dose of study treatment
* 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.
* Subjects with a known hypersensitivity to any component of the OKZ drug product, adalimumab, or placebo
* Subjects with a known hypersensitivity or contraindication to any component of the rescue medication
* History of severe allergic or anaphylactic reactions to human, humanized, or murine monoclonal antibodies

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

Primary outcomes:
measure: Percentage of Subjects Achieving American College of Rheumatology 20% (ACR20) Response
timeFrame: at Week 12
Secondary outcomes:
measure: Percentage of Subjects Achieving ACR20 Response: Olokizumab Comparison With Adalimumab
timeFrame: at Week 12
measure: Percentage of Subjects Achieving Low Disease Activity
timeFrame: at Week 12
measure: Percentage of Subjects Achieving Low Disease Activity: Olokizumab Comparison With Adalimumab
timeFrame: at Week 12
measure: Improvement of Physical Ability From Baseline to Week 12, as Measured by the Health Assessment Questionnaire-Disability Index (HAQ-DI)
timeFrame: Baseline to Week 12
measure: Percentage of Subjects Achieving American College of Rheumatology 50% (ACR50) Response
timeFrame: at Week 24
measure: Percentage of Subjects With Clinical Disease Activity Index (CDAI) ≤ 2.8 (Remission)
timeFrame: at Week 24
Other outcomes:
Locations:
city: Mesa
country: United States
facility: Arizona Arthritis & Rheumatology Associates, P.C.
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: Covina
country: United States
facility: Medvin Clinical Research
state: California
city: El Cajon
country: United States
facility: TriWest Research Associates
state: California
city: Hemet
country: United States
facility: MD Med Corp.
state: California
city: Los Alamitos
country: United States
facility: Valerius Medical Group
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: Santa Maria
country: United States
facility: Pacific Arthritis Center Medical Grpoup
state: California
city: Upland
country: United States
facility: Inland Rheumatology Clinical Trials
state: California
city: West Hills
country: United States
facility: Center for Rheumatology Research
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, Inc.
state: Florida
city: Miami
country: United States
facility: Medical Research Center of Miami
state: Florida
city: Orlando
country: United States
facility: Omega Research Consultants
state: Florida
city: Palm Harbor
country: United States
facility: Arthritis Research
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: Springfield
country: United States
facility: Springfield Clinic, LLP
state: Illinois
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: 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 Instutute-Rheumatology
state: Montana
city: Lincoln
country: United States
facility: Physician Resrch Collaboration
state: Nebraska
city: Freehold
country: United States
facility: Arthritis & Osteoporosis Associates, PA
state: New Jersey
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: Minot
country: United States
facility: Trinity Medical Group
state: North Dakota
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: 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: Beaumont
country: United States
facility: Pioneer Research Solutions, Inc.
state: Texas
city: Grapevine
country: United States
facility: Precision Comprehensive Clinical Research Solutions
state: Texas
city: Houston
country: United States
facility: Rheumatology Clinic of Houston, P.A.
state: Texas
city: Houston
country: United States
facility: Accurate Clinical Research
state: Texas
city: Houston
country: United States
facility: Accurate Clinical Mangemnt LLC
state: Texas
city: Houston
country: United States
facility: Accurate Clinical Research, Inc.
state: Texas
city: Houston
country: United States
facility: Advanced Rheumatology of Houston
state: Texas
city: League City
country: United States
facility: Accurate Clinical Research, Inc.
state: Texas
city: Lubbock
country: United States
facility: Endocrinology, Internal Medicine
state: Texas
city: San Antonio
country: United States
facility: Dr. Alex De Jesus Rheumatology, P.A.
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: Mar del Plata
country: Argentina
facility: Instituto de Investigaciones Clinicas-Mar del Plata
state: Buenos Aires
city: Quilmes
country: Argentina
facility: Instituto Medico CER
state: Buenos Aires
city: Rosario
country: Argentina
facility: Clinica de Higado y Aparato Digestivo
state: Santa Fe
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: San Miguel de Tucuman
country: Argentina
facility: Centro de Investigaciones Reumatológicas
state: Tucuman
city: Buenos Aires
country: Argentina
facility: Institute Investigaciones Clinc Quilme
city: Ciudad Autonoma Buenos Aires
country: Argentina
facility: Atencion Integral en Reumatologia (AIR)
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 S.A
city: Cordoba
country: Argentina
facility: Instituto DAMIC Fundacion Rusculleda
city: San Juan
country: Argentina
facility: CER San Juan Centro Polivalente de Asistencia e Inv. Clinica
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: Porto Alegre
country: Brazil
facility: LMK Serviços Médicos S/S Ltda
state: Rio Grande Do Sul
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: Santa Catarina
country: Brazil
facility: Clínica de Neoplasias Litoral
city: São Paulo
country: Brazil
facility: CPCLIN - Centro de Pesquisas Clínicas Ltda.
city: São Paulo
country: Brazil
facility: Hospital Abreu Sodré - AACD
city: Plovdiv
country: Bulgaria
facility: UMHAT Pulmed OOD
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 Investigacion Medico
state: Atlantico
city: Bogota
country: Colombia
facility: Fundacion Instituto de Reumatologia Fernando Chalem
city: Bogotá
country: Colombia
facility: Centro de Investigacion en Reumatologia y Especialidades Medicas SAS. CIREEM
city: Bucaramanga
country: Colombia
facility: Medicity S.A.S.
city: Cali
country: Colombia
facility: Clinica de Artritis Temprana S.A.
city: Brno
country: Czechia
facility: CCR Brno 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 Pardubice
city: Praha 10
country: Czechia
facility: Clintrial, s.r.o.
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: Revmatologicky ustav
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 Services s.r.o.
city: Tallinn
country: Estonia
facility: East Tallinn Central Hospital
city: Tartu
country: Estonia
facility: Medita Kliinik OÜ
city: Bad Nauheim
country: Germany
facility: Kerckhoff-Klinik gGmbH
state: Hessen
city: Magdeburg
country: Germany
facility: SMO.MD GmbH
state: Sachsen Anhalt
city: Aachen
country: Germany
facility: Rheumapraxis Dr. med. Reiner Kurthen
state: Westfalen
city: Berlin
country: Germany
facility: Klinische Forschung Berlin-Mitte GmbH
city: Hamburg
country: Germany
facility: HRF Hamburger Rheuma Forschungszentrum
city: Northeim
country: Germany
facility: Studienambulanz Dr. Wassenberg
city: Baja
country: Hungary
facility: Principal SMO Kft.
city: Balatonfured
country: Hungary
facility: DRC Gyogyszervizsgalo Kozpont Kft.
city: Budapest
country: Hungary
facility: Clinexpert Egeszsegugyi Szolg. es Ker. Kft.
city: Budapest
country: Hungary
facility: Obudai Egeszsegugyi Centrum
city: Kiskunhalas
country: Hungary
facility: Kiskunhalasi Semmelweis Korhaz
city: Szekesfehervar
country: Hungary
facility: DRC Szekesfehervar
city: Szolnok
country: Hungary
facility: MAV Korhaz és Rendelointezet
city: Veszprem
country: Hungary
facility: Vital Medical Center
city: Daejeon
country: Korea, Republic of
facility: Eulji University Hospital
city: Gwangju
country: Korea, Republic of
facility: Chonnam National University Hospital
city: Gyeonggi-do
country: Korea, Republic of
facility: CHA Bundang Medical Center
city: Jeju
country: Korea, Republic of
facility: Jeju National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University
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: Alytаus 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 Clinic, Public Institution
city: Mexico
country: Mexico
facility: Centro de Investigacion Clínica GRAMEL S.C
state: DisMexicotrito Federal
city: Mexico
country: Mexico
facility: Clinstile, S.A. de C.V.
state: Distrito Federal
city: Mexico
country: Mexico
facility: Clinicos Asociados BOCM S.C.
state: Distrito Federal
city: Mexico
country: Mexico
facility: Cryptex Investigacion Clinica S.C
state: Distrito Federal
city: Mexico City
country: Mexico
facility: Clinical Research Institute S.C.
state: Estado De Mexico
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: San Luis Potosi
country: Mexico
facility: Centro de Alta Especialidad en Reumatología e Investigación del Potosí, S.C.
city: Bialystok
country: Poland
facility: NZOZ 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 PodrażkaSzczepaniak S.C.
city: Kielce
country: Poland
facility: Polimedica Centrum Badań, Profilaktyki I Leczenia
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: CCBR - Lodz - PL
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: Niepubliczny Zaklad Opieki Zdrowotnej "Nasz Lekarz" Praktyka Grupowa Lekarzy Rodzinnych z
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: Constanta
country: Romania
facility: Spitalul Clinic Judetean de Urgenta "Sf. Apostol Andrei" Constanta
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: FSBEI HE "FMSMU n.a. I.M. Sechenov of MoH of RF", University Hospital #2, Departament of New Drugs Introduction
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: Nizhniy Novgorod
country: Russian Federation
facility: SBHI of Nizhny Novgorod Region "Nizhny Novgorod Regional Clinical Hospital n.a.Semashko"
state: Nizhegorodskaya Oblast
city: Ufa
country: Russian Federation
facility: Hospital n a Kuvatov
state: Republic Of Bashkortostan
city: Petrozavodsk
country: Russian Federation
facility: SBHI of Republic of Karelia "Republican Hospital named after V.A.Baranov"
state: Republic Of Karelia
city: Smolensk
country: Russian Federation
facility: Non-govarnmental Healtheare Institution "Regional Clinical Hospital at Smolensk station of OJSC "Russian Railways"
state: Smolenskaya Oblast
city: Ekaterinburg
country: Russian Federation
facility: State Budgetary Healthcare Institution of Sverdlovsk Region "Sverdlovsk Regional Clinical Hospital #1"
state: Sverdlovskaya Oblast
city: Ekaterinburg
country: Russian Federation
facility: SBEI HPE "Ural State Medical University" of MoH of RF based MBI "Central City Clinical Hospital #6"
state: Sverdlovskaya Oblast
city: Moscow
country: Russian Federation
facility: Institute n a Nasonova
city: Tainan
country: Taiwan
facility: Chi Mei Medical Center
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: R-Pharm
name: Mikhail Samsonov
role: STUDY_DIRECTOR
References:
citation: Smolen JS, Feist E, Fatenejad S, Grishin SA, Korneva EV, Nasonov EL, Samsonov MY, Fleischmann RM; CREDO2 Group. Olokizumab versus Placebo or Adalimumab in Rheumatoid Arthritis. N Engl J Med. 2022 Aug 25;387(8):715-726. doi: 10.1056/NEJMoa2201302.