Evaluation of the Efficacy and Safety of Two Dosing Regimens of Olokizumab (OKZ), Compared to Placebo, in Subjects With Rheumatoid Arthritis (RA) Who Were Taking an Existing Medication Called a Tumour Necrosis Factor Alpha Inhibitor But Had Active Disease

Phase 3

Completed

Conditions: Rheumatoid Arthritis

Interventions: Drug: Olokizumab
Drug: Placebo

Registration Number: NCT02760433

Lead Sponsor: R-Pharm International, LLC

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 an existing medication called a tumour necrosis factor alpha inhibitor

The primary objective of this study was to evaluate the efficacy of olokizumab (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 rheumatoid arthritis (RA) inadequately controlled by TNF-α inhibitor (TNFi) 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 TNFi therapy. The primary endpoint of the trial was assessed 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 was a randomized, double-blind, parallel-group, placebo-controlled, multicenter study. This study included a 4-week Screening Period, a double-blind Treatment Period from Week 0 to Week 24, and a Safety FollowUp Period from Week 24 to Week 44.

A total of 350 subjects were planned to be randomized.Subjects were assessed for eligibility to enter the study during a 4-week Screening Period. Eligible subjects were randomized at Visit 2 in a 2:2:1 ratio in one of 3 treatment groups (planned 140, 140, and 70 subjects per group, respectively) :

1. Olokizumab 64 mg q4w: SC injection of OKZ 64 mg q4w (alternating with SC injection of placebo OKZ q4w to maintain blinding) + MTX for 24 weeks,

2. Olokizumab 64 mg q2w: SC injection of OKZ 64 mg q2w + MTX for 24 weeks or

3. Placebo: SC injection of placebo q2w + MTX for 16 weeks.

Subjects who received placebo were re-randomized at Week 16 to receive 64 mg OKZ q4w + Methotrexate or 64 mg OKZ q2w +Methotrexate for 8 weeks.

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 OKZ was administered at Week 20 for subjects receiving OKZ 64 mg q4w and at Week 22 for subjects receiving OKZ 64 mg q2w.

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 did not improve 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 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 123 sites across 11 countries globally (in US,EU, Russian Federation, Asia, Latin America)

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 368

Inclusion Criteria

Subjects may be enrolled in the study only if they meet all of the following 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 24 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.)

Treatment with oral, SC, or intramuscular (IM) MTX for at least 12 weeks prior to Screening at a dose of 15 to 25 mg/week (or ≥10 mg/week if there is documented intolerance to higher doses)
- The dose and means of administering MTX must have been stable for at least 6 weeks prior to Screening.
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
- C-reactive protein (CRP) above Upper limit of normal (ULN) at Screening based on the central laboratory results.
Subjects must have a documented inadequate response to treatment (i.e., TNFi failure) with ≥1 licensed TNFi following at least 12 weeks of therapy with that agent. Inadequate response to treatment is classified as either:
- Primary failure: The absence of any documented clinically significant response; or
- Secondary failure: Documented initial response with subsequent loss of that response or partial response

Exclusion Criteria

Diagnosis of any other inflammatory arthritis or systemic rheumatic disease (e.g., gout, psoriatic or reactive arthritis, Crohn's disease, Lyme disease, juvenile idiopathic arthritis, or systemic lupus erythematosus) (However, subjects may 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 Interleukin (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) with the exception of rituximab, which is allowed if it was discontinued at least 24 weeks prior to baseline (rituximab 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).
Prior use of bDMARDs, within the following windows prior to baseline (bDMARDs 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 etanercept and anakinra
2. 8 weeks for infliximab
3. 10 weeks for adalimumab, certolizumab, and golimumab
4. 12 weeks for abatacept
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])

a) subjects who are positive for hepatitis B surface antibodies (anti-HBs), but negative for HBsAg and anti-HBc, will be eligible.
Subjects with HIV infection
Subjects with:
1. Suspected or confirmed current active tuberculosis (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
Subjects with a known hypersensitivity to any component of the OKZ drug product 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
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 the 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

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.

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm 1: Olokizumab q4w	Olokizumab	Olokizumab 64mg subcutaneous q4w + placebo + Methotrexate Olokizumab 64 mg subcutaneous q4w + placebo+ concomitant background therapy (Methotrexate) at a stable dose with a stable route of administration (oral, subcutaneous, or intramuscular) in order to maintain the blind, subjects randomized to receive OKZ q4w received placebo injections at the alternate q4w interval (e.g., Week 2, Week 6, etc.)
Arm 3: Placebo q2w	Placebo	Placebo q2w subcutaneous + Methotrexate Placebo administered subcutaneously once every 2 weeks + concomitant background therapy (Methotrexate) at a stable dose with a stable route of administration (oral, subcutaneous, or intramuscular) Starting at Week 16, all subjects in the placebo group were randomized in a blinded fashion to receive either OKZ 64 mg q2w or OKZ 64 mg q4w; equal numbers of subjects were planned to be assigned to each OKZ treatment group.
Arm 1: Olokizumab q4w	Placebo	Olokizumab 64mg subcutaneous q4w + placebo + Methotrexate Olokizumab 64 mg subcutaneous q4w + placebo+ concomitant background therapy (Methotrexate) at a stable dose with a stable route of administration (oral, subcutaneous, or intramuscular) in order to maintain the blind, subjects randomized to receive OKZ q4w received placebo injections at the alternate q4w interval (e.g., Week 2, Week 6, etc.)
Arm 2: Olokizumab q2w	Olokizumab	Olokizumab 64mg subcutaneous q2w + Methotrexate 64 mg Olokizumab administered subcutaneously once every 2 weeks + concomitant background therapy (Methotrexate) at a stable dose with a stable route of administration (oral, subcutaneous, or intramuscular)

Primary Outcome Measures

Name	Time	Method
Percentage of Subjects Achieving American College of Rheumatology 20% (ACR20) Response	at Week 12	The difference between OKZ and placebo in the percentage of subjects achieving an ACR20 response and remaining on randomized treatment and in the study at Week 12. A responder is defined as any subject satisfying ACR20 criteria and remaining on randomized treatment and in the study at Week 12. American College of Rheumatology 20 % response is a composite defined as a ≥ 20% improvement from baseline in the swollen joint counts assessed in 66 joints and in the tender joint count assessed in 68 joints; and a ≥20% improvement from baseline in at least 3 of the 5 remaining core set measures: * Patient Global Assessment of Disease Activity (VAS) * Patient Assessment of Pain (VAS) * HAQ-DI * Physician Global Assessment (VAS) * Level of acute phase reactant (CRP)

Secondary Outcome Measures

Name	Time	Method
Percentage of Subjects Achieving Low Disease Activity	at Week 12	Defined as Disease Activity Score 28-joint count (DAS28) C-reactive protein (CRP) \<3.2, and remaining on randomized treatment and in the study at Week 12
Percentage of Subjects Achieving American College of Rheumatology 50% (ACR50) Response	at Week 12	Difference between OKZ and placebo in the percentage of subjects achieving an ACR50 response and remaining on randomized treatment and in the study at Week 12. American College of Rheumatology 50% Response is a composite defined as ≥50%, improvement from baseline in the swollen joint counts assessed in 66 joints and in the tender joint count assessed in 68 joints; and a ≥50%, improvement from baseline in at least 3 of the 5 remaining core set measures: * Patient Global Assessment of Disease Activity (VAS) * Patient Assessment of Pain (VAS) * HAQ-DI * Physician Global Assessment (VAS) * Level of acute phase reactant (CRP)
Improvement of Physical Ability From Baseline to Week 12, as Measured by the Health Assessment Questionnaire Disability Index (HAQ-DI)	Baseline to Week 12	Change of physical ability from baseline (the last available assessment prior to the first dose of the study treatment) to week 12, as measured by HAQ-DI. The HAQ-DI assesses the degree of difficulty experienced in 8 domains of daily living activities using 20 questions.The domains are dressing and grooming, arising, eating, walking, hygiene, reach, grip and common daily activities, and each domain consists of 2 or 3 items. For each question, the level of difficulty is scored from 0 to 3 where 0 = without any difficulty (the best outcome), 1 = with some difficulty, 2 = much difficulty, and 3 = unable to do (the worst outcome). Each category is given a score by taking the maximum score of each question. A decrease from baseline indicates improvement for HAQ-DI.The HAQ-DI was calculated by dividing the sum of the category scores by the number of categories with at least 1 question answered. The HAQ-DI total score ranges from 0 (the best outcome) to 3 (the worst outcome).
Percentage of Subjects With Clinical Disease Activity Index (CDAI) ≤ 2.8 (Remission)	at Week 12	Difference between OKZ and placebo in the percentage of subjects with Clinical Disease Activity Index (CDAI) ≤2.8 (remission) and remaining on randomized treatment and in the study at Week 12

Trial Locations

Locations (114): CEDOES - Diagnóstico e Pesquisa
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Vitória, Espírito Santo, Brazil
CMiP - Centro Mineiro de Pesquisa
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Juiz de Fora, Minas Gerais, Brazil
Hospital Bruno Born
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Lajeado, Rio Grande Do Sul, Brazil
LMK Serviços Médicos S/S Ltda
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Porto Alegre, Rio Grande Do Sul, Brazil
Centro de Reumatologia y Ortopedia SAS
🇨🇴
Barranquilla, Colombia
Medicity S.A.S.
🇨🇴
Bucaramanga, Colombia
Clinica de Artritis Temprana S.A.
🇨🇴
Cali, Colombia
Centro de Investigacion en Reumatologia y Especialidades Medicas SAS. CIREEM
🇨🇴
Bogotá, Colombia
Sanatorio San Martin
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Venado Tuerto, Santa Fe, Argentina
CETI - Centro de Estudos em Terapias Inovadoras Ltda.
🇧🇷
Curitiba, Paraná, Brazil
Centro de Investigacion Clínica GRAMEL S.C
🇲🇽
Mexico, Distrito Federal, Mexico
CHI St. Vincent Hot Springs
🇺🇸
Hot Springs, Arkansas, United States
Graves Gilbert Clinic
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Bowling Green, Kentucky, United States
Precision Comprehensive Clinical Research Solutions
🇺🇸
Grapevine, Texas, United States
Hospital Privado Centro Medico de Cordoba S.A
🇦🇷
Cordoba, Argentina
Clinica de Higado y Aparato Digestivo
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Rosario, Santa Fe, Argentina
Centro de Investigaciones Reumatológicas
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San Miguel de Tucuman, Tucuman, Argentina
Faculdade de Medicina do ABC
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Santo André, Sao Paulo, Brazil
CCR Czech, a.s.
🇨🇿
Pardubice, Czechia
McM Polimedica
🇵🇱
Warszawa, Poland
MAV Korhaz és Rendelointezet
🇭🇺
Szolnok, Hungary
Vital Medical Center
🇭🇺
Veszprem, Hungary
MEDICAL PLUS s.r.o.
🇨🇿
Uherske Hradiste, Czechia
Clinstile, S.A. de C.V.
🇲🇽
Mexico, Distrito Federal, Mexico
Investigacion y Biomedicina de Chihuahua, S.C.
🇲🇽
Chihuahua, Mexico
Centrum Medyczne AMED
🇵🇱
Lodz, Poland
Rostov State Medical Unversity
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Rostov-on-Don, Rostov Oblast, Russian Federation
Centro de Estudios de Investigacion Basica y Clinica SC
🇲🇽
Guadalajara, Jalisco, Mexico
Regional Clinical Hospital
🇷🇺
Vladimir, Vladimir Oblast, Russian Federation
Chonnam National University Hospital
🇰🇷
Gwangju, Korea, Republic of
SBHI of Stavropol Region "Stavropol Regional Clinical Hospital"
🇷🇺
Stavropol', Stavropol Region, Russian Federation
Medvin Clinical Research
🇺🇸
Covina, California, United States
TriWest Research Associates, LLC
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El Cajon, California, United States
Advanced Medical Research, LLC
🇺🇸
Lakewood, California, United States
Stanford University School of Medicine
🇺🇸
Palo Alto, California, United States
Inland Rheumatology Clinical Trials, Inc.
🇺🇸
Upland, California, United States
Javed Rheumatology Associates
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Newark, Delaware, United States
The Arthritis & Diabetes Clinic, Inc.
🇺🇸
Monroe, Louisiana, United States
University of Kansas Hospital
🇺🇸
Kansas City, Kansas, United States
Clinical Pharmacology Study Group
🇺🇸
Worcester, Massachusetts, United States
The Center for Rheumatology and Bone Research
🇺🇸
Wheaton, Maryland, United States
Arthritis & Osteoporosis Associates, PA
🇺🇸
Freehold, New Jersey, United States
Carolina Arthritis Associates
🇺🇸
Wilmington, North Carolina, United States
Lovelace Scientific Resources, Inc.
🇺🇸
Albuquerque, New Mexico, United States
Cape Fear Arthritis Care
🇺🇸
Leland, North Carolina, United States
NYU Langone Ambulatory Care
🇺🇸
New York, New York, United States
Trinity Medical Group
🇺🇸
Minot, North Dakota, United States
STAT Research, Inc.
🇺🇸
Dayton, Ohio, United States
Clinical Research Source, Inc.
🇺🇸
Perrysburg, Ohio, United States
Accurate Clinical Research, Inc.
🇺🇸
League City, Texas, United States
Amarillo Center for Clinical Research
🇺🇸
Amarillo, Texas, United States
Endocrinology, Internal Medicine
🇺🇸
Lubbock, Texas, United States
Centro de Investigaciones Medicas Mar del Plata
🇦🇷
Mar del Plata, Buenos Aires, Argentina
Advanced Rheumatology of Houston
🇺🇸
Woodville, Texas, United States
Instituto de Investigaciones Clinicas
🇦🇷
Mar del Plata, Buenos Aires, Argentina
Instituto de Investigaciones Clinicas Quilmes
🇦🇷
Quilmes, Buenos Aires, Argentina
Centro Medico Privado de Reumatologia
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San Miguel de Tucuman, Tucuman, Argentina
Associação de Assistência à Criança Deficiente - AACD
🇧🇷
Sao Paulo, Brazil
Organizacion Medica de Investigacion (OMI)
🇦🇷
Ciudad Autonoma Buenos Aires, Argentina
APRILLUS
🇦🇷
Ciudad Autonoma Buenos aires, Argentina
Centro Polivalente de Asistencia e Inv. Clinica CER
🇦🇷
San Juan, Argentina
HUWC - UFC - Hospital Universitário Walter Cantídio - Universidade Federal do Ceará
🇧🇷
Fortaleza, Ceará, Brazil
Instituto Centenario
🇦🇷
Ciudad Autonoma Buenos Aires, Argentina
CIP - Centro Internacional de Pesquisa
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Goiânia, Goiás, Brazil
Centro Multidisciplinar de Estudos Clínicos - CEMEC
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Sao Bernardo Do Campo, Sao Paulo, Brazil
Clínica de Neoplasias Litoral Ltda.
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Santa Catarina, Brazil
CPCLIN - Centro de Pesquisas Clínicas Ltda.
🇧🇷
São Paulo, Brazil
Atencion Integral en Reumatologia (AIR)
🇦🇷
Ciudad Autonoma Buenos Aires, Argentina
Revmatologie MUDr. Klara Sirova s.r.o.
🇨🇿
Ostrava - Moravska Ostrava, Czechia
PV - Medical, s.r.o.
🇨🇿
Zlin, Czechia
Kerckhoff-Klinik gGmbH
🇩🇪
Bad Nauheim, Hessen, Germany
SMO.MD GmbH
🇩🇪
Magdeburg, Sachsen Anhalt, Germany
HRF Hamburger Rheuma Forschungszentrum
🇩🇪
Hamburg, Germany
Clinexpert Egeszsegugyi Szolg. es Ker. Kft.
🇭🇺
Budapest, Hungary
Obudai Egeszsegugyi Centrum
🇭🇺
Budapest, Hungary
Ajou University Hospital
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Suwon-si, Gyeonggi-do, Korea, Republic of
Hallym University Sacred Heart Hospital
🇰🇷
Gyeonggi-do, Korea, Republic of
Severance Hospital, Yonsei University
🇰🇷
Seoul, Korea, Republic of
Centro de Alta Especialidad en Reumatología e Investigación del Potosí, S.C.
🇲🇽
San Luis Potosi, San Luis Potos, Mexico
Szpital Uniwersytecki nr 2 im.dr J. Biziela
🇵🇱
Bydgoszcz, Poland
McBk S.C.
🇵🇱
Grodzisk Mazowiecki, Poland
Szpital Wojewodzki im. Prymasa Kardynala Stefana Wyszynskiego
🇵🇱
Sieradz, Poland
State Budgetary Healthcare Institution "City Clinical Hospital # 15 n.a O.M. Filatov" of Moscow Healtheare Department
🇷🇺
Moscow, Moscow Region, Russian Federation
City Clinical Hospital #1
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Novosibirsk, Novosibirsk Oblast, Russian Federation
Diagnostic Center Ultramed
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Omsk, Omsk Oblast, Russian Federation
SBHI of the Republic of Karelia "Republican Hospital named after V.A.Baranov"
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Petrozavodsk, Republic Of Karelia, Russian Federation
FSBSI "Scientific Research Institute of Rheumatology n.a. V.A. Nasonova"
🇷🇺
Moscow, Russian Federation
Riverside Medical Clinic
🇺🇸
Riverside, California, United States
RASF - Clinical Research Center
🇺🇸
Boca Raton, Florida, United States
Arthritis Group
🇺🇸
Philadelphia, Pennsylvania, United States
Accelerium S. de R.L. de C.V.
🇲🇽
Monterrey, Nuevo León, Mexico
Samodzielny Publiczny ZOZ Tomaszow Lubelski
🇵🇱
Tomaszow Lubelski, Poland
Arizona Arthritis & Rheumatology Associates, P.C.
🇺🇸
Phoenix, Arizona, United States
Saint Jude Heritage Medical Grp
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Fullerton, California, United States
С V Mehta MD Med Corp.
🇺🇸
Hemet, California, United States
East Bay Rheumatology Medical Group, Inc.
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San Leandro, California, United States
Denver Arthritis Clinic
🇺🇸
Denver, Colorado, United States
Suncoast Research Group LLC
🇺🇸
Miami, Florida, United States
Omega Research Consultants
🇺🇸
Orlando, Florida, United States
Family Clinical Trials, LLC.
🇺🇸
Pembroke Pines, Florida, United States
AdventHealth Medical Group, PA
🇺🇸
Tampa, Florida, United States
Institute of Arthritis Research
🇺🇸
Idaho Falls, Idaho, United States
Glacier View Research Instutute-Rheumatology
🇺🇸
Kalispell, Montana, United States
Dr. Alex De Jesus Rheumatology, P.A.
🇺🇸
San Antonio, Texas, United States
Universidad Autonoma de Nuevo Leon, Hospital Universitario Dr. Jose Eleuterio Gonzalez
🇲🇽
Monterrey, Nuevo León, Mexico
Klein and Associates, M.D., P.A.
🇺🇸
Hagerstown, Maryland, United States
Medication Management, LLC
🇺🇸
Greensboro, North Carolina, United States
Cincinnati Rheumatic Disease Study Group
🇺🇸
Cincinnati, Ohio, United States
Low Country Research Center
🇺🇸
Charleston, South Carolina, United States
Austin Regional Clinic, P.A.
🇺🇸
Austin, Texas, United States
Therapeutic Concepts Rheumatology, LLC
🇺🇸
Houston, Texas, United States
Rheumatology Clinic of Houston, P.A.
🇺🇸
Houston, Texas, United States
Pioneer Research Solutions, Inc.
🇺🇸
Houston, Texas, United States
Clinica de Investigacion en Reumatologia y Obesidad S.C.
🇲🇽
Guadalajara, Jalisco, Mexico