Efficacy and Safety of Olokizumab in Subjects With Moderately to Severely Active Rheumatoid Arthritis
- Conditions
- Rheumatoid Arthritis
- Interventions
- Registration Number
- NCT03120949
- Lead Sponsor
- R-Pharm International, LLC
- 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).
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 2106
Subjects may be enrolled in the study only if they meet all of the following criteria:
- Subject must be willing and able to sign informed consent
- Subject must have completed the 24-week double-blind Treatment Period in 1 of the 3 core studies (CL04041022, CL04041023, or CL04041025).
- 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
- Subjects must be willing to take folic acid or equivalent throughout the study.
-
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.
-
Subject has evidence of active tuberculosis (TB)
-
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:
- 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);
- 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
- The subject is willing to complete the entire course of recommended LTBI therapy.
-
Subject has planned surgery during the first 12 weeks of the OLE study
-
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
-
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
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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.
-
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Subject is unwilling or unable to follow the procedures outlined in the protocol.
-
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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Treatment Arm 2: OKZ 64 mg q2w + MTX Olokizumab 64 mg SC q2w Olokizumab 64 mg SC q2w + concomitant background therapy (Methotrexate) at a stable dose with a stable route of administration (oral, subcutaneous, or intramuscular). Treatment Arm 1: OKZ 64 mg q4w + MTX Olokizumab 64 mg SC q4w Olokizumab 64 mg SC q4w + concomitant background therapy (Methotrexate) at a stable dose with a stable route of administration (oral, subcutaneous, or intramuscular). Treatment Arm 1: OKZ 64 mg q4w + MTX Concomitant treatment Olokizumab 64 mg SC q4w + concomitant background therapy (Methotrexate) at a stable dose with a stable route of administration (oral, subcutaneous, or intramuscular). Treatment Arm 2: OKZ 64 mg q2w + MTX Concomitant treatment Olokizumab 64 mg SC q2w + concomitant background therapy (Methotrexate) at a stable dose with a stable route of administration (oral, subcutaneous, or intramuscular).
- Primary Outcome Measures
Name Time Method Incidence Rate of Treatment Emergent AESIs (Safety Population) up to Week 126 Incidence Rate of all Subjects with at Least One Treatment Emergent AESI. Subject Incidence Rate (IR) is summarized per 100 subject years (SY) of follow-up (/100 SY) based on the OLE safety population and presented by study treatments.
Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) up to Week 126 Incidence of Serious Treatment-Emergent Adverse Events by System Organ Class or Preferred Term.
Deaths are included.Incidence of Treatment-Emergent AEs Leading to Withdrawal of the Study Treatment up to Week 126 Incidence of Treatment-Emergent Adverse Events of Special Interest (AESI) up to Week 126 Incidence of Treatment-Emergent Adverse Events (AEs), by System Organ Class and Preferred Term (Safety Population) up to Week 126 Incidence of Treatment-Emergent Adverse Events Reported for ≥5% of Subjects in Any Treatment Group by System Organ Class or Preferred Term
Incidence Rate of Treatment Emergent AEs Per Patient-years of Exposure up to Week 126 Incidence Rate of all Subjects with at Least One Treatment Emergent AE. Subject Incidence Rate (IR) is summarized per 100 subject years (SY) of follow-up (/100 SY) based on the OLE safety population and presented by study treatments.
Incidence Rate of Treatment Emergent SAEs Per Patient-years of Exposure up to Week 126 Incidence Rate of all Subjects with at Least One Treatment Emergent SAE. Subject Incidence Rate (IR) is summarized per 100 subject years (SY) of follow-up (/100 SY) based on the OLE safety population and presented by study treatments.
- Secondary Outcome Measures
Name Time Method American College of Rheumatology 50% (ACR50) Response Rates Compare Against Core Baseline Through Week 82 up to Week 82 Number and Proportion of subjects achieving an ACR50 response who remain on randomized open-label treatment and in the study, assessed at several timepoints up to Week 82
American College of Rheumatology 50 % response is a composite defined as a ≥ 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)Change in Health Assessment Questionnaire-Disability Index (HAQ-DI) From Core Baseline at Week 40 Core baseline, Week 40 HAQ-DI Range: 0 (the best outcome) - 3 (the worst outcome), with a decrease from baseline indicating improvement.
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 (activity) 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 (i.e., question in each category with the highest score for that category). The HAQ-DI was calculated by dividing the sum of the category scores by the number of categories with at least 1 question answered.Change in Health Assessment Questionnaire-Disability Index (HAQ-DI) From Core Baseline at Week 12 Core baseline, Week 12 HAQ-DI Range: 0 (the best outcome) - 3 (the worst outcome), with a decrease from baseline indicating improvement.
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 (activity) 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 (i.e., question in each category with the highest score for that category). The HAQ-DI was calculated by dividing the sum of the category scores by the number of categories with at least 1 question answered.Change in Health Assessment Questionnaire-Disability Index (HAQ-DI) From Core Baseline at Week 28 Core baseline, Week 28 HAQ-DI Range: 0 (the best outcome) - 3 (the worst outcome), with a decrease from baseline indicating improvement.
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 (activity) 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 (i.e., question in each category with the highest score for that category). The HAQ-DI was calculated by dividing the sum of the category scores by the number of categories with at least 1 question answered.Change in Health Assessment Questionnaire-Disability Index (HAQ-DI) From Core Baseline at Week 52 Core baseline, Week 52 HAQ-DI Range: 0 (the best outcome) - 3 (the worst outcome), with a decrease from baseline indicating improvement.
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 (activity) 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 (i.e., question in each category with the highest score for that category). The HAQ-DI was calculated by dividing the sum of the category scores by the number of categories with at least 1 question answered.American College of Rheumatology 20% (ACR20) Response Rates Compare Against Core Baseline Through Week 82 up to Week 82 Number and Proportion of subjects achieving an ACR20 response who remain on randomized open-label treatment and in the study, assessed at several timepoints up to Week 82.
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)Proportion of Subjects With Simplified Disease Activity Index (SDAI) Remission Through Week 82 up to week 82 The number and proportion of subjects with SDAI score ≤ 3.3 (considered to be in remission).
The SDAI was calculated in the statistical database for analysis purposes using the SJC (28 joints), TJC (28 joints), CRP (mg/dL), the Patient Global Assessment of Disease Activity (VAS) (in cm), and the Physician Global Assessment (VAS) (in cm) according to the following formula: SJC + TJC + Patient Global Assessment of Disease Activity (VAS) + Physician Global Assessment (VAS) + CRP (mg/dL)Change in Health Assessment Questionnaire-Disability Index (HAQ-DI) From Core Baseline at Week 20 Core baseline, Week 20 HAQ-DI Range: 0 (the best outcome) - 3 (the worst outcome), with a decrease from baseline indicating improvement.
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 (activity) 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 (i.e., question in each category with the highest score for that category). The HAQ-DI was calculated by dividing the sum of the category scores by the number of categories with at least 1 question answered.American College of Rheumatology 70% (ACR70) Response Rates Compare Against Core Baseline Through Week 82 up to Week 82 Number and Proportion of subjects achieving an ACR70 response who remain on randomized open-label treatment and in the study, assessed at several timepoints up to Week 82
American College of Rheumatology 70 % response is a composite defined as a ≥ 70% improvement from baseline in the swollen joint counts assessed in 66 joints and in the tender joint count assessed in 68 joints; and a ≥ 70% 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)Disease Activity Score 28-joint Count (DAS28) Response Rates Through Week 82 up to Week 82 Number and Proportion of subjects with DAS28 low disease activity (based on DAS28 C-reactive protein (CRP) \< 3.2), who remain on randomized open-label treatment and in the study, assessed at several timepoints up to Week 82.
The DAS28 (CRP) was calculated in the statistical database for analysis purposes using the Swollen joint count (SJC) (28 joints), Tender joint count (TJC) (28 joints), CRP level, and the Patient Global Assessment of Disease Activity Visual Analog Scale (VAS) (100 mm VAS, where 0 is "no disease activity" and 100 was "maximal disease activity") according to the following formula: \[0.56 × square root of TJC\] + \[0.28 × square root of SJC\] + \[0.36 × natural log (CRP+1)\] + \[0.014 × VAS\] + 0.96.Change in Health Assessment Questionnaire-Disability Index (HAQ-DI) From Core Baseline at Week 82 Core baseline, Week 82 HAQ-DI Range: 0 (the best outcome) - 3 (the worst outcome), with a decrease from baseline indicating improvement.
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 (activity) 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 (i.e., question in each category with the highest score for that category). The HAQ-DI was calculated by dividing the sum of the category scores by the number of categories with at least 1 question answered.Proportion of Subjects With Health Assessment Questionnaire - Disability Index (HAQ-DI) Improvement Through Week 82 up to week 82 The number and proportion of subjects with HAQ-DI improvement ≥ 0.22 Against OLE Baseline.
HAQ-DI Range: 0 (the best outcome) - 3 (the worst outcome), with a decrease from baseline indicating improvement.
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 (activity) 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 (i.e., question in each category with the highest score for that category). The HAQ-DI was calculated by dividing the sum of the category scores by the number of categories with at least 1 question answered.Change in Health Assessment Questionnaire-Disability Index (HAQ-DI) From Core Baseline at Week 64 Core baseline, Week 64 HAQ-DI Range: 0 (the best outcome) - 3 (the worst outcome), with a decrease from baseline indicating improvement.
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 (activity) 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 (i.e., question in each category with the highest score for that category). The HAQ-DI was calculated by dividing the sum of the category scores by the number of categories with at least 1 question answered.Changes From Core Baseline Over Time in Clinical Disease Activity Index (CDAI) up to week 82 CDAI Range: 0 (the best outcome) - 76 (the worst outcome), with a decrease from baseline indicating improvement.
The CDAI was calculated in the statistical database for analysis purposes using the SJC (28 joints), TJC (28 joints), the Patient Global Assessment of Disease Activity (VAS) (in cm), and the Physician Global Assessment (VAS) (in cm) according to the following formula: CDAI = SJC + TJC + Patient Global Assessment of Disease Activity (VAS) + Physician Global Assessment (VAS)
Trial Locations
- Locations (234)
C.V Mehta MD Med Corp..
🇺🇸Hemet, California, United States
New England Research Associates LLC
🇺🇸Bridgeport, Connecticut, United States
Family Clinical Trials, LLC.
🇺🇸Pembroke Pines, Florida, United States
Marietta Rheumatology Associates, PC
🇺🇸Marietta, Georgia, United States
Glacier View Research Institute-Rheumatology
🇺🇸Kalispell, Montana, United States
Arthritis Group
🇺🇸Philadelphia, Pennsylvania, United States
Accelerium S. de R.L. de C.V.
🇲🇽Monterrey, Nuevo León, Mexico
Medizinski Zentar-1-Sevlievo EOOD
🇧🇬Sevlievo, Bulgaria
Clinica de Investigacion en Reumatologia y Obesidad S.C.
🇲🇽Guadalajara, Jalisco, Mexico
Investigacion y Biomedicina de Chihuahua, S.C.
🇲🇽Chihuahua, Mexico
Budgetary Healthcare Institution "Kursk Regional Clinical Hospital" of Healthcare Committee of Kursk region
🇷🇺Kursk, Kurskaya Oblast, Russian Federation
FSAEI HE "First MSMU n.a. I.M. Sechenov of the Ministry of Health of the Russian Federation" University Clinical Hospital No.1
🇷🇺Moscow, Moscovskaya Oblast, Russian Federation
State Autonomous Helthcare Institution of Yaroslavl region "Clinical Hospital of Emergency Care n.a. Solovyev"
🇷🇺Yaroslavl, Yaroslavsakaya Oblast, Russian Federation
SBHI of Vladimir Region "Regional Clinical Hospital", Rheumatology Departament
🇷🇺Vladimir, Vladimirskaya Oblast, Russian Federation
UMHAT "Sv. Ivan Rilski", EAD
🇧🇬Sofia, Bulgaria
Rheumapraxis Dr. med. Reiner Kurthen
🇩🇪Aachen, Nordrhein Westfalen, Germany
Clinexpert Kft.
🇭🇺Budapest, Hungary
ETYKA Osrodek Badan Klinicznych
🇵🇱Olsztyn, Poland
Nasz lekarz Przychodnie Medyczne
🇵🇱Torun, Poland
FSAEI HE "First MSMU n.a. I.M. Sechenov of the Ministry of Health of the Russian Federation"
🇷🇺Moscow, Russian Federation
SBHI of Moscow "City Clinical Hospital #4 of Moscow Healthcare Departament"
🇷🇺Moscow, Moskovskaya Oblast, Russian Federation
FSBEI HE "Rostov State Medical Unversity" of Ministry of Health of the Russian Federation
🇷🇺Rostov, Rostovskaya Oblast, Russian Federation
Rheumatology Clinic of Houston, P.A.
🇺🇸Houston, Texas, United States
Hospital Bruno Born
🇧🇷Lajeado, Rio Grande Do Sul, Brazil
CMiP - Centro Mineiro de Pesquisa
🇧🇷Juiz de Fora, Minas Gerais, Brazil
Trinity Medical Group
🇺🇸Minot, North Dakota, United States
LMK Serviços Médicos S/S Ltda
🇧🇷Pôrto Alegre, Rio Grande Do Sul, Brazil
Maidstone Hospital
🇬🇧Maidstone, Kent, United Kingdom
CEDOES - Diagnóstico e Pesquisa
🇧🇷Vitória, Espírito Santo, Brazil
Arizona Arthritis & Rheumatology Associates, P.C.
🇺🇸Phoenix, Arizona, United States
East Bay Rheumatology Medical Group, Inc.
🇺🇸San Leandro, California, United States
AZ Arthritis & Rheum' Research
🇺🇸Mesa, Arizona, United States
Arizona Arthritis & Rheumatology Research, PLLC
🇺🇸Sun City, Arizona, United States
CHI St. Vincent Hot Springs
🇺🇸Hot Springs, Arkansas, United States
Medvin Clinical Research
🇺🇸Whittier, California, United States
Advanced Medical Research, LLC
🇺🇸La Palma, California, United States
Valerius Medical Group
🇺🇸Los Alamitos, California, United States
Stanford University School of Medicine
🇺🇸Palo Alto, California, United States
Rheumatology Center of San Diego
🇺🇸San Diego, California, United States
Inland Rheumatology Clinical Trials, Inc.
🇺🇸Upland, California, United States
Denver Arthritis Clinic
🇺🇸Denver, Colorado, United States
Center for Rheumatology Research, Comprehensive Rheumatology Center
🇺🇸West Hills, California, United States
RASF - Clinical Research Center
🇺🇸Boca Raton, Florida, United States
Javed Rheumatology Associates
🇺🇸Newark, Delaware, United States
Medical Research Center of Miami
🇺🇸Miami, Florida, United States
Reliable Clinical Research, LLC
🇺🇸Hialeah, Florida, United States
Pharmax Research Clinic
🇺🇸Miami, Florida, United States
Suncoast Research Group, LLC
🇺🇸Miami, Florida, United States
Arthritis Research of Florida, INC
🇺🇸Palm Harbor, Florida, United States
AdventHealth Medical Group, PA
🇺🇸Tampa, Florida, United States
Arthritis Center of North Georgia
🇺🇸Gainesville, Georgia, United States
Institute of Arthritis Research
🇺🇸Idaho Falls, Idaho, United States
University of Kansas Hospital
🇺🇸Kansas City, Kansas, United States
Graves Gilbert Clinic
🇺🇸Bowling Green, Kentucky, United States
The Arthritis & Diabetes Clinic, Inc.
🇺🇸Monroe, Louisiana, United States
Clinical Pharmacology Study Group
🇺🇸Worcester, Massachusetts, United States
Klein and Associates, M.D., P.A.
🇺🇸Hagerstown, Maryland, United States
AA MRC LLC Ahmed Arif Medical Research Center
🇺🇸Grand Blanc, Michigan, United States
The Center for Rheumatology and Bone Research
🇺🇸Wheaton, Maryland, United States
North MS Medical Clinics, Inc.
🇺🇸Tupelo, Mississippi, United States
Physician Research Collaboration
🇺🇸Lincoln, Nebraska, United States
Arthritis & Osteoporosis Associates, PA
🇺🇸Freehold, New Jersey, United States
Cincinnati Rheumatic Disease Study Group
🇺🇸Cincinnati, Ohio, United States
STAT Research, Inc.
🇺🇸Dayton, Ohio, United States
Cape Fear Arthritis Care
🇺🇸Leland, North Carolina, United States
Medication Management, LLC
🇺🇸Greensboro, North Carolina, United States
NYU Langone ambulatory care
🇺🇸Brooklyn, New York, United States
Carolina Arthritis Associates
🇺🇸Wilmington, North Carolina, United States
Clinical Research Source, Inc.
🇺🇸Toledo, Ohio, United States
Lynn Health Science Institute
🇺🇸Oklahoma City, Oklahoma, United States
Health Research of Oklahoma, PLLC
🇺🇸Oklahoma City, Oklahoma, United States
Altoona Center for Clinical Research, P.C.
🇺🇸Duncansville, Pennsylvania, United States
Low Country Rheumatology, PA
🇺🇸Summerville, South Carolina, United States
Precision Comprehensive Clinical Research Solutions
🇺🇸Colleyville, Texas, United States
Amarillo Center for Clinical Research
🇺🇸Amarillo, Texas, United States
Accurate Clinical Management., LLC
🇺🇸Baytown, Texas, United States
Therapeutic Concepts Rheumatology,LLC
🇺🇸Houston, Texas, United States
Houston Institute For Clinical Research
🇺🇸Houston, Texas, United States
Pioneer Research Solutions, Inc.
🇺🇸Cypress, Texas, United States
Accurate Clinical Mangemnt - Partner
🇺🇸Houston, Texas, United States
Dr Alex De Jesus Rheumatology, P.A.
🇺🇸San Antonio, Texas, United States
Accurate Clinical Research, Inc.
🇺🇸League City, Texas, United States
West Texas Clinical Research
🇺🇸Lubbock, Texas, United States
Advanced Rheumatology of Houston
🇺🇸The Woodlands, Texas, United States
Centro de Investigaciones Medicas Mar del Plata
🇦🇷Mar del Plata, Buenos Aires, Argentina
DM Clinical Research
🇺🇸Tomball, Texas, United States
Arthritis Northwest, PLLC
🇺🇸Spokane, Washington, United States
Instituto Medico CER
🇦🇷Quilmes, Buenos Aires, Argentina
Sanatorio San Martin
🇦🇷Venado Tuerto, Santa Fe, Argentina
Instituto de Investigaciones Clinicas Quilmes
🇦🇷Quilmes, Buenos Aires, Argentina
Centro Medico Privado de Reumatologia
🇦🇷San Miguel de Tucuman, Tucuman, Argentina
Instituto de Investigaciones Clinicas-Mar del Plata
🇦🇷Buenos Aires, Argentina
Organizacion Medica de Investigacion (OMI)
🇦🇷Ciudad Autonoma Buenos Aires, Argentina
Instituto Centenario
🇦🇷Ciudad Autonoma Buenos Aires, Argentina
Hospital Privado Centro Medico de Cordoba
🇦🇷Cordoba, Argentina
Instituto DAMIC Fundacion Rusculleda
🇦🇷Córdoba, Argentina
APRILLUS Asistencia e Investigacion
🇦🇷Ciudad Autonoma Buenos aires, Argentina
CER San Juan Centro Polivalente de Asistencia e Inv. Clinica
🇦🇷San Juan, Argentina
Centro de Investigaciones Reumatológicas
🇦🇷Tucuman, Argentina
Minsk City Clinical Hospital #1
🇧🇾Minsk, Minsk Oblast, Belarus
Vitebsk Clinical Hospital
🇧🇾Vitebsk, Vitebsk Oblast, Belarus
Clinica de Higado y Aparato Digestivo
🇦🇷Santa Fe, Argentina
HUWC - UFC - Hospital Universitário Walter Cantídio - Universidade Federal do Ceará
🇧🇷Fortaleza, Ceará, Brazil
CIP - Centro Internacional de Pesquisa
🇧🇷Goiânia, Goiás, Brazil
Clinilive - Clínica do Idoso e Pesquisa Clínica
🇧🇷Maringá, Paraná, Brazil
CETI - Centro de Estudos em Terapias Inovadoras Ltda.
🇧🇷Curitiba, Paraná, Brazil
Clínica de Neoplasias Litoral Ltda.
🇧🇷Itajaí, Santa Catarina, Brazil
Centro Multidisciplinar de Estudos Clínicos - CEMEC
🇧🇷Sao Bernardo Do Campo, Sao Paulo, Brazil
CCBR Brasil Centro de Pesquisas e Análises Clínicas Ltda.
🇧🇷Rio de Janeiro, Brazil
Faculdade de Medicina do ABC
🇧🇷Santo André, Sao Paulo, Brazil
CPCLIN - Centro de Pesquisas Clínicas Ltda.
🇧🇷São Paulo, Brazil
UMHAT "Kaspela", EOOD
🇧🇬Plovdiv, Bulgaria
MHAT - Ruse, AD
🇧🇬Ruse, Bulgaria
DCC 'Sv. Pantaleymon' OOD
🇧🇬Pleven, Bulgaria
Associação de Assistência à Criança Deficiente - AACD
🇧🇷São Paulo, Brazil
UMHAT Pulmed OOD
🇧🇬Plovdiv, Bulgaria
MHAT - Shumen, AD
🇧🇬Shumen, Bulgaria
NMTH "Tsar Boris III"
🇧🇬Sofia, Bulgaria
Medical Center "Excelsior", OOD
🇧🇬Sofia, Bulgaria
MHAT "Lyulin", EAD
🇧🇬Sofia, Bulgaria
MDHAT 'Dr. Stefan Cherkezov', AD
🇧🇬Veliko Tarnovo, Bulgaria
Centro de Reumatologia y Ortopedia SAS
🇨🇴Barranquilla, Colombia
MC "Synexus - Sofia", EOOD
🇧🇬Sofia, Bulgaria
Centro de Investigacion en Reumatologia y Especialidades Medicas SAS. CIREEM
🇨🇴Bogotá, Colombia
Clinica de Artritis Temprana S.A.S
🇨🇴Cali, Colombia
Fundacion Instituto de Reumatologia Fernando Chalem
🇨🇴Bogotá, Colombia
Medicity S.A.S.
🇨🇴Bucaramanga, Colombia
IMEDICA s.r.o.
🇨🇿Brno, Czechia
CCR Brno s.r.o
🇨🇿Brno, Czechia
Revmatologie s.r.o.
🇨🇿Brno, Czechia
MUDr Gabriela Simkova Ordinace Lekare Specialisty Interna Revmatologie
🇨🇿Kladno, Czechia
CTCenter MaVe s.r.o.
🇨🇿Olomouc, Czechia
Nemocnice Jihlava p.o.
🇨🇿Jihlava, Czechia
ARTROSCAN s.r.o.
🇨🇿Ostrava - Trebovice, Czechia
ARTHROHELP s.r.o.
🇨🇿Pardubice, Czechia
Vesalion s.r.o.
🇨🇿Ostrava, Czechia
CCR Czech, a.s.
🇨🇿Pardubice, Czechia
Revmatologicky ustav
🇨🇿Praha 2, Czechia
CLINTRIAL s.r.o.
🇨🇿Praha, Czechia
CCR Prague s.r.o.
🇨🇿Praha 3, Czechia
Fakultni nemocnice v Motole
🇨🇿Praha 5, Czechia
MUDR Zuzana URBANOVA Revmatologie
🇨🇿Praha 4, Czechia
DRC Szekesfehervar
🇭🇺Székesfehérvár, Hungary
Affidea Praha s.r.o.
🇨🇿Praha, Czechia
Medical Plus s.r.o.
🇨🇿Uherske Hradiste, Czechia
PV - MEDICAL, s.r.o.
🇨🇿Zlin, Czechia
Kerckhoff-Klinik gGmbH
🇩🇪Bad Nauheim, Hessen, Germany
East Tallinn Central Hospital
🇪🇪Tallinn, Estonia
Meditrials OU
🇪🇪Tartu, Estonia
Studienambulanz Dr. Wassenberg
🇩🇪Ratingen, Nordrhein Westfalen, Germany
SMO.MD GmbH
🇩🇪Magdeburg, Sachsen Anhalt, Germany
Klinische Forschung Berlin-Mitte GmbH
🇩🇪Berlin, Germany
Principal SMO Kft.
🇭🇺Baja, Hungary
HRF Hamburger Rheuma Forschungszentrum
🇩🇪Hamburg, Germany
DRC Gyogyszervizsgalo Kozpont Kft.
🇭🇺Balatonfüred, Hungary
Obudai Egeszsegugyi Centrum Kft.
🇭🇺Budapest, Hungary
Kiskunhalasi Semmelweis Korhaz
🇭🇺Kiskunhalas, Hungary
MAV Korhaz es Rendelointezet
🇭🇺Szolnok, Hungary
Vital-Medicina Kft.
🇭🇺Veszprem, Hungary
Hallym University Sacred Heart Hospital
🇰🇷Anyang-si, Gyeonggi-do, Korea, Republic of
Eulji University Hospital
🇰🇷Daejeon, Korea, Republic of
Ajou University Hospital
🇰🇷Suwon-si, Gyeonggi-do, Korea, Republic of
Chonnam National University Hospital
🇰🇷Gwangju, Korea, Republic of
Jeju National University Hospital
🇰🇷Jeju, Korea, Republic of
The Catholic University of Korea, Seoul St. Mary's Hospital
🇰🇷Seoul, Korea, Republic of
Severance Hospital, Yonsei University No. 31 Office, Pediatric Oncology Clinic
🇰🇷Seoul, Korea, Republic of
Alytus Regional S. Kudirkos Hospital, Public Institution
🇱🇹Alytus, Lithuania
Dr.Saulite-Kandevica Private Practice
🇱🇻Liepaja, Latvia
Republican Kaunas Hospital, Public Institution
🇱🇹Kaunas, Lithuania
Klaipeda University Hospital, Public Institution
🇱🇹Klaipeda, Lithuania
Center Outpatient Clinic, Public Institution
🇱🇹Vilnius, Lithuania
Siauliai Republican Hospital, Public Institution
🇱🇹Siauliai, Lithuania
Clinicos Asociados BOCM S.C.
🇲🇽Mexico, Distrito Federal, Mexico
Vilnius University Hospital Santariskiu Clinics, Public Institution
🇱🇹Vilnius, Lithuania
Centro de Investigacion Clínica GRAMEL S.C
🇲🇽Mexico, Distrito Federal, Mexico
Comite Mexicano Para la Prevencion de Osteoporosis AC
🇲🇽Mexico, Distrito Federal, Mexico
Clinstile, S.A. de C.V.
🇲🇽Mexico, Distrito Federal, Mexico
Centro de Estudios de Investigacion Basica y Clinica SC
🇲🇽Guadalajara, Jalisco, Mexico
Universidad Autonoma de Nuevo Leon, Hospital Universitario Dr. Jose Eleuterio Gonzalez
🇲🇽Monterrey, Nuevo León, Mexico
Clinical Research Institute S.C.
🇲🇽Mexico City, Mexico
Centro de Alta Especialidad en Reumatología e Investigación del Potosí, S.C.
🇲🇽San Luis Potosí, Mexico
CERMED
🇵🇱Bialystok, Poland
ZDROWIE Osteo-Medic
🇵🇱Bialystok, Poland
Polimedica Centrum Badań, Profilaktyki I Leczenia
🇵🇱Kielce, Poland
Centrum Medyczne AMED
🇵🇱Lodz, Poland
Szpital Uniwersytecki nr 2 im.dr J. Biziela
🇵🇱Bydgoszcz, Poland
MCBK Iwona Czajkowska Anna Podrażka- Szczepaniak S.C.
🇵🇱Grodzisk Mazowiecki, Poland
CCBR - Lodz - PL
🇵🇱Lodz, Poland
Clinmed Research
🇵🇱Skierniewice, Poland
Szpital Wojewodzki im. Prymasa Kardynala Stefana Wyszynskiego
🇵🇱Sieradz, Poland
Samodzielny Publiczny ZOZ Tomaszow Lubelski
🇵🇱Tomaszow Lubelski, Poland
RCMed
🇵🇱Sochaczew, Poland
KO-MED Centra Kliniczne Staszow
🇵🇱Staszow, Poland
Rheuma Medicus Zaklad Opieki Zdrowotnej
🇵🇱Warszawa, Poland
Medycyna Kliniczna
🇵🇱Warszawa, Poland
Santa Familia Centrum Badan, Profilaktyki i Leczenia
🇵🇱Zgierz, Poland
SAHI of Kemerovo region "Regional Clinical Hospital for War Veterans"
🇷🇺Kemerovo, Kemerovskaya Oblast, Russian Federation
Medical Center LLC "Maksimum Zdoroviya"
🇷🇺Kemerovo, Kemerovo Oblast, Russian Federation
McM Polimedica
🇵🇱Warszawa, Poland
SPb SBHI "Clinical Rheumatological Hospital #25", Fourth Rheumatology Unit
🇷🇺Saint Petersburg, Leningradskaya Oblast, Russian Federation
KO-MED Centra Kliniczne Zamosc
🇵🇱Zamosc, Poland
FSBEI HE "Altai State Medical University of the Ministry of Healthcare of Russian Federation"
🇷🇺Barnaul, Altai Region, Russian Federation
SBHI of Moscow "City Clinical Hospital No.1 n.a. Pirogov" Healthcare Department of Moscow
🇷🇺Moscow, Moscovskaya Oblast, Russian Federation
State Budgetary Healthcare Institution "City Clinical Hospital # 15 n.a O.M. Filatov" of Moscow Healtheare Department
🇷🇺Moscow, Moscow Region, Russian Federation
SBHI of Nizhegorodsky Region "State Clinical Hospital #5 of Nizhegorodsky District of Nizhny Novgorod"
🇷🇺Nizhny Novgorod, Nizhny Novgorod Oblast, Russian Federation
SBHI of Nizhny Novgorod Region "Nizhny Novgorod Regional Clinical Hospital n.a.Semashko"
🇷🇺Nizhniy Novgorod, Nizhegorodskaya Oblast, Russian Federation
Budgetary Healthcare Institution of Omsk Region "Regional Clinical Hospital"
🇷🇺Omsk, Omskaya Oblast, Russian Federation
LLC "Clinical Diagnostic Center "Ultramed"
🇷🇺Omsk, Omskaya Oblast, Russian Federation
State Autonomous Healthcare Institution of Novosibirsk region "City Polyclinic #1"
🇷🇺Novosibirsk, Novosibirsk Oblast, Russian Federation
SBHI of the Republic of Karelia "Republican Hospital named after V.A. Baranov"
🇷🇺Petrozavodsk, Republic Of Karelia, Russian Federation
State Budgetary Healthcare Institution "Republican Clinical Hospital n.a. G.G. Kuvatov"
🇷🇺Ufa, Respublic Of Bashkortostan, Russian Federation
FSBEI HE 'Ryazan State Medical University n.a. I.P.Pavlov" of the Ministry of Health of Russian Federation
🇷🇺Ryazan, Ryazan Oblast, Russian Federation
State Healthcare Institution "Regional Clinical Hospital"
🇷🇺Saratov, Saratovskaya Oblast, Russian Federation
FSBEI HE "Saratov SMU n.a. V.I.Razumovsky of Ministry of Health of Russian Federation"
🇷🇺Saratov, Saratovskaya Oblast, Russian Federation
Private Healthcare Institution "Clinical Hospital Russian Railways-Medicine of City Smolensk"
🇷🇺Smolensk, Smolenskaya Oblast, Russian Federation
FSBEI HE StSMU MOH Russia based on SBHI of Stavropol Region "Stavropol Regional Clinical Hospital"
🇷🇺Stavropol', Stavropol Region, Russian Federation
State Autonomous Healthcare Institution of Sverdlovsk Region "Sverdlovsk Regional Clinical Hospital No.1"
🇷🇺Ekaterinburg, Sverdlovskaya Oblast, Russian Federation
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"
🇷🇺Kazan', The Republic Of Tatarstan, Russian Federation
FSBEI HE "Ural State Medical University" of Ministry of Health of Russian Federation based on MBI "Central City Clinical Hospital No.6"
🇷🇺Ekaterinburg, Sverdlovskaya Oblast, Russian Federation
State Healthcare Institution of Tula region "Tula Regional Clinical Hospital"
🇷🇺Tula, Tulskaya Oblast, Russian Federation
State Healthcare Institution "Ulyanovsk Regional Clinical Hospital"
🇷🇺Ulyanovsk, Ulyanovskaya Oblast, Russian Federation
SBHI "Yaroslavl Regional Clinical Hospital", Rheumatology department
🇷🇺Yaroslavl', Yaroslavskaya Oblast, Russian Federation
FSBI "National Medical Research Center n.a. V.A.Almazov" of the Ministry of Healthcare of the Russian Federation
🇷🇺Saint Petersburg, Russian Federation
FSBSI "Scientific Research Institute of Rheumatology n.a. V.A. Nasonova"
🇷🇺Moscow, Russian Federation
Chi Mei Medical Center, Yung Kang Branch
🇨🇳Tainan, Taiwan
Chang Gung Memorial Hospital, Linkou
🇨🇳Taoyuan, Taiwan
Torbay Hospital
🇬🇧Torquay, Devon, United Kingdom
Whipps Cross University Hospital
🇬🇧London, Greater London, United Kingdom
Basingstoke and North Hampshire Hospital
🇬🇧Basingstoke, Hampshire, United Kingdom
Royal Free Hospital
🇬🇧London, Greater London, United Kingdom
Arrowe Park Hospital
🇬🇧Wirral, Merseyside, United Kingdom
Omega Research Consultants
🇺🇸Orlando, Florida, United States
Austin Regional Clinic, P.A.
🇺🇸Austin, Texas, United States
Lovelace Scientific Resources, Inc.
🇺🇸Albuquerque, New Mexico, United States