A Comparative Study Between PF-06410293 and Humira® in Combination With Methotrexate in Participants With Active Rheumatoid Arthritis
- Registration Number
- NCT04230213
- Lead Sponsor
- Pfizer
- Brief Summary
The study will assess the impact of pharmacokinetics (PK), safety and immunogenicity after switches between PF-06410293 and adalimumab and with continuous dosing with adalimumab in combination with methotrexate in subjects with moderately to severely active rheumatoid arthritis.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 455
- Diagnosis of RA based on 2010 ACR/EULAR for RA for at least a 4 month duration.
- Moderately to severely active RA based on local standard of care.
-Evidence of untreated or inadequately treated latent or active TB.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Treatment Arm 1 PF-06410293 Subcutaneous (SC) injection given every other week Treatment Arm 1 adalimumab Subcutaneous (SC) injection given every other week Treatment Arm 2 adalimumab SC injection given every other week
- Primary Outcome Measures
Name Time Method Maximum Observed Serum Concentration (Cmax) of Adalimumab Pre-dose, 48, 72, 96, 144, 240 and 336 hours post dose on Day 211 (Week 30) Cmax refers to maximum observed serum concentration of drug. The geometric coefficient of variation is expressed in percentage.
Area Under the Serum Concentration-Time Curve Over the Dosing Interval (AUCtau) of Adalimumab Pre-dose, 48, 72, 96, 144, 240 and 336 hours post dose on Day 211 (Week 30) Area under the serum concentration curve from time 0 to end of dosing interval (tau), where dosing interval was once every two weeks. The geometric coefficient of variation is expressed in percentage.
- Secondary Outcome Measures
Name Time Method Time to Reach Cmax (Tmax) of Adalimumab Pre-dose, 48, 72, 96, 144, 240 and 336 hours post dose on Day 211 (Week 30) Tmax is the time taken (in hours) to reach the maximum serum drug concentration.
Apparent Clearance (CL/F) of Serum Adalimumab Pre-dose, 48, 72, 96, 144, 240 and 336 hours post dose on Day 211 (Week 30) Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. CL/F was calculated as dose administered divided by area under the concentration curve from time 0 extrapolated to infinite time (AUCinf). The geometric coefficient of variation is expressed in percentage.
Pre-dose Serum Concentration During Multiple Dosing (Ctrough) of Adalimumab Pre-dose on Day 1, 71,113, 155, 169, 183, 197 and 211 Ctrough was defined as pre-dose serum concentration during multiple dosing and observed directly from data.
Mean NAb Titers Week 10, 16, 22, 24, 26, 28, 30, 32 Serum samples were analyzed using a validated ECL immunoassay for ADA assessment. Endpoint titer was defined as log10 of the reciprocal of the NAb serum dilution at which the sample response was equal to the cut-point of the assay.
Average Serum Concentration (Cav) of Adalimumab Pre-dose, 48, 72, 96, 144, 240 and 336 hours post dose on Day 211 (Week 30) Cav was defined as average serum concentration over the dosing interval. The geometric coefficient of variation is expressed in percentage.
Mean ADA Titers Week 10, 16, 22, 24, 26, 28, 30, 32 Serum samples were analyzed using a validated ECL immunoassay for ADA assessment. Endpoint titer was defined as log10 of the reciprocal of the ADA serum dilution at which the sample response was equal to the cut-point of the assay.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs and Treatment Related TEAEs: TP1 Day 1 up to maximum of 10 Weeks An adverse event (AE) was any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An SAE was any untoward medical occurrence that, at any dose: resulted in death; required inpatient hospitalization or prolongation of existing hospitalization; was life-threatening; resulted in persistent or significant disability/ incapacity; congenital anomaly/birth defect and other important medical events. Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. TEAE for TP1 was defined as any AE that occurred after the beginning of study treatment in TP1 and before the first dose of study treatment administration after randomization in TP2. AEs included both serious and all non-serious AEs.
Number of Participants With TEAEs, Serious TEAEs and Treatment Related TEAEs: TP2 and Beyond Post randomization up to maximum of 4 weeks after last dose (maximum of 26 weeks) An AE was any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An SAE was any untoward medical occurrence that, at any dose: resulted in death; required inpatient hospitalization or prolongation of existing hospitalization; was life-threatening; resulted in persistent or significant disability/ incapacity; congenital anomaly/birth defect and other important medical events. Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. TEAE for TP2 and beyond was defined as any AE that occurred after administering the first dose of study treatment after randomization in TP2 and up to 4 weeks after last dose. AEs included both serious and all non-serious AEs.
Number of Participants With Grade 3 or Higher TEAEs: TP1 Day 1 up to maximum of 10 Weeks An AE was any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. TEAE for TP1 was defined as any AE that occurred after the beginning of study treatment in TP1 and before the first dose of study treatment administration after randomization in TP2. AEs were graded using the Common Terminology Criteria for Adverse Events where, grade 1=mild AE; grade 2=moderate AE; grade 3=severe AE; grade 4= life-threatening consequences; urgent intervention indicated; and grade 5= death related to AE. Number of participants with grade 3 or higher TEAEs were presented.
Number of Participants With Grade 3 or Higher TEAEs: TP2 and Beyond Post randomization up to maximum of 4 weeks after last dose (maximum of 26 weeks) An AE was any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. TEAE for TP2 and beyond was defined as any AE that occurred after the first dose of study treatment administration after randomization in TP2 and up to 4 weeks after last dose. AEs were graded using the Common Terminology Criteria for Adverse Events where, grade 1=mild AE; grade 2=moderate AE; grade 3=severe AE; grade 4= life-threatening consequences; urgent intervention indicated; and grade 5= death related to AE. Number of participants with grade 3 or higher TEAEs were presented.
Number of Participants Who Discontinued Treatment and Study Due to TEAEs: TP1 Day 1 up to maximum of 10 Weeks An AE was any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. TEAE for TP1 was defined as any AE that occurred after the beginning of study treatment in TP1 and before the first dose of study treatment administration after randomization in TP2. Participants who discontinued treatment due to TEAEs were those who had an AE record indicating that action taken with study treatment was drug withdrawn but AE did not cause the participant to be discontinued from study. Participants who discontinued from study due to TEAE were those who had an TEAE in TP1 indicating that the AE caused the participant to be discontinued from the study.
Number of Participants Who Were Anti-Drug Antibodies (ADA) Positive and Neutralizing Antibodies (NAb) Positive Week 10, 16, 22, 24, 26, 28, 32 Serum samples were analyzed using a validated electrochemoluminescent (ECL) immunoassay for ADA assessment. Samples positive for ADA were further tested for neutralizing activity using a validated cell based NAb assay. ADA positive was defined as ADA titer \>=1.88 while NAb positive was defined as NAb titer \>=0.70.
Number of Participants Who Discontinued Treatment and Study Due to TEAEs: TP2 and Beyond Post randomization up to maximum of 4 weeks after last dose (maximum of 26 weeks) An AE was any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. TEAE for TP2 and beyond was defined as any AE that occurred after the first dose of study treatment administration after randomization in TP2 and up to 4 weeks after last dose. AEs included both serious and all non-serious AEs. Participants who discontinued treatment due to TEAEs were those who had an AE record indicating that action taken with study treatment was drug withdrawn but AE did not cause the participant to be discontinued from study. Participants who discontinued from study due to TEAE were those who had an AE record indicating that the AE caused the participant to be discontinued from the study.
Number of Participants With TEAEs of Special Interest: TP2 and Beyond Post randomization up to maximum of 4 weeks after last dose (maximum of 26 weeks) AEs of special interest (AESI) included: hypersensitivity events (anaphylactic reaction, hypersensitivity, angioedema, delayed immune responses and injection site reactions \[ISRs\]); blood and lymphatic system events (white blood cell disorders and anemias nonhemolytic and marrow depression); cardiovascular events (cardiac failure, hypertension and myocardial infarction); demyelinating conditions, gastric/hepatic events (gastrointestinal perforation, ulceration, hemorrhage or obstruction and hepatic disorders); infections and infestations (including TB and other opportunistic infections); malignancies (neoplasms benign, malignant and unspecified \[including cysts and polyps\]) and lupus like syndrome. TEAE was defined as any AE that occurred after the first dose of study treatment administered after randomization in TP2. Number of participants with any AESI were presented in this outcome measure.
Number of Participants With Potential Immunogenic AEs to Study Treatment: TP2 and Beyond Among Anti-drug Antibody (ADA) Positive Participants During TP1 TP2 and Beyond: Week 16, 22, 24, 26, 28, 30, 32 In this outcome, participants who were antidrug antibody (ADA) positive during TP1 were assessed in TP2 and beyond per visit for their ADA status at the time of start of their potential immunogenic AEs including ISRs, medically evaluated board standard MedDRA query (SMQ) of potential hypersensitivity (anaphylactic reactions, hypersensitivity and angioedema), medically evaluated AEs meeting Sampson criteria, cytokine storm and delayed immune responses (DIR). ADA positive was defined as ADA titer \>=1.88.
Number of Participants With Potential Immunogenic AEs to Study Treatment: TP2 and Beyond Among ADA Negative Participants During TP1 TP2 and Beyond: Week 16, 22, 24, 26, 28, 30, 32 In this outcome, participants who were ADA negative during TP1 were assessed in TP2 and beyond per visit for their ADA status at the time of start of their potential immunogenic AEs including ISRs, medically evaluated board SMQ of potential hypersensitivity (anaphylactic reactions, hypersensitivity and angioedema), medically evaluated AEs meeting Sampson criteria, cytokine storm and DIR. ADA negative was defined as ADA titer \<1.88.
Number of Participants With TEAEs and Serious TEAEs Related to COVID-19: TP1 Day 1 up to maximum of 10 Weeks An AE was any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An SAE was any untoward medical occurrence that, at any dose: resulted in death; required inpatient hospitalization or prolongation of existing hospitalization; was life-threatening; resulted in persistent or significant disability/ incapacity; congenital anomaly/birth defect and other important medical events. TEAE for TP1 was defined as any AE that occurred after the beginning of study treatment in TP1 and before the first dose of study treatment administration after randomization in TP2. AEs included both serious and all non-serious AEs. TEAEs and serious TEAEs related to Covid-19 as per investigator's assessment were presented.
Number of Participants With TEAEs and Serious TEAEs Related to COVID-19: TP2 and Beyond Post randomization up to maximum of 4 weeks after last dose (maximum of 26 weeks) An AE was any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An SAE was any untoward medical occurrence that, at any dose: resulted in death; required inpatient hospitalization or prolongation of existing hospitalization; was life-threatening; resulted in persistent or significant disability/ incapacity; congenital anomaly/birth defect and other important medical events. TEAE for TP2 and beyond was defined as any AE that occurred after the first dose of study treatment administration after randomization in TP2 and up to 4 weeks after last dose. AEs included both serious and all non-serious AEs. TEAEs and serious TEAEs related to Covid-19 as per investigator's assessment were presented.
Number of Participants Who Discontinued Treatment and Study Due to TEAEs Related to COVID-19: TP1 Day 1 up to maximum of 10 Weeks An AE was any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. TEAE for TP1 was defined as any AE that occurred after the beginning of study treatment in TP1 and before the first dose of study treatment administration after randomization in TP2. Participants who discontinued treatment due to TEAEs were those who had an AE record indicating that action taken with study treatment was drug withdrawn but AE did not cause the participant to be discontinued from study. Participants who discontinued from study due to TEAE were those who had an AE record indicating that the AE caused the participant to be discontinued from the study. TEAEs were related to Covid-19.
Number of Participants Who Discontinued Treatment and Study Due to TEAEs Related to COVID-19: TP2 and Beyond Post randomization up to maximum of 4 weeks after last dose (maximum of 26 weeks) An AE was any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. TEAE for TP2 and beyond was defined as any AE that occurred after the first dose of study treatment administration after randomization in TP2 and up to 4 weeks after last dose. AEs included both serious and all non-serious AEs. Participants who discontinued treatment due to TEAEs were those who had an AE record indicating that action taken with study treatment was drug withdrawn but AE did not cause the participant to be discontinued from study. Participants who discontinued from study due to TEAE were those who had an AE record indicating that the AE caused the participant to be discontinued from the study. TEAEs were related to Covid-19.
Number of Participants With Laboratory Abnormalities: TP1 Day 1 up to maximum of 10 Weeks Blood samples were collected for the analysis of following laboratory parameters: hematology parameters (hemoglobin, erythrocyte mean corpuscular volume, erythrocyte mean corpuscular hemoglobin, erythrocyte mean corpuscular hemoglobin concentration platelet count, leukocytes, lymphocytes, neutrophils, eosinophils, monocytes); clinical chemistry parameters (bilirubin, alanine aminotransferase \[ALT\], blood urea nitrogen \[BUN\], creatinine, potassium, bicarbonate); urine parameters: urine protein, urine hemoglobin, nitrite, leukocyte esterase and bacteria. Number of participants with any laboratory abnormalities is presented.
Number of Participants With Laboratory Abnormalities: TP2 and Beyond Post randomization up to end of study treatment (maximum of 22 weeks) Blood samples were collected for the analysis of following laboratory parameters: hematology parameters (hemoglobin, erythrocyte mean corpuscular volume, erythrocyte mean corpuscular hemoglobin, erythrocyte mean corpuscular hemoglobin concentration platelet count, leukocytes, lymphocytes, neutrophils, eosinophils, monocytes); clinical chemistry parameters (bilirubin, ALT, BUN, creatinine, potassium, bicarbonate); urine parameters: urine protein, urine hemoglobin, nitrite, leukocyte esterase and bacteria. Number of participants with any laboratory abnormalities is presented.
Number of Participants With Hematology Results by Maximum Common Toxicity Criteria (CTC) Grade: TP2 and Beyond Post randomization up to end of study treatment (maximum of 22 weeks) Blood samples were collected for the analysis of following hematology parameters: anemia, hemoglobin increased, leukocytosis, lymphocyte count decreased, lymphocyte count increased, neutrophil count decreased, platelet count decreased, white blood cell decreased. Laboratory parameters were graded according to National Cancer Institute-CTC version 4.03 where, Grade 0= within normal limits; Grade1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences and Grade 5: death. Categories with at least 1 non-zero value were reported in this outcome measure.
Number of Participants With Chemistry Results by Maximum CTC Grade: TP2 and Beyond Post randomization up to end of study treatment (maximum of 22 weeks) Blood samples were collected for analysis of clinical chemistry parameters: ALT increased, alkaline phosphatase increased (ALP), aspartate aminotransferase increased (AST), blood bilirubin increased, creatinine increased, hypercalcemia, hyperkalemia, hypernatremia, hypoalbuminemia, hypocalcemia, hypokalemia, hyponatremia. Laboratory parameters were graded according to NCI-CTC version 4.03 where, grade 0= within normal limits; Grade1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences and Grade 5: death. Categories with at least 1 non-zero value were reported.
Number of Participants With Laboratory Results Based on Evaluation of Drug-Induced Serious Hepatotoxicity (eDISH) Analysis: TP2 and Beyond Post randomization up to end of study treatment (maximum of 22 weeks) In this outcome measure, liver function laboratory parameters, which included: normal bilirubin and AST/ALT, Temple's Corollary (AST/ALT \[more than or equal to\] \>=3\*upper limit normal \[ULN\] and normal bilirubin), Gilbert's Syndrome or cholestasis (normal AST/ALT and bilirubin \>=2\*ULN) and Potential Hy's Law Cases (AST/ALT \>=3\*ULN and Bilirubin\>=2\*ULN) according to eDISH criteria, were reported.
Baseline, Absolute Week 32 Values for Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Change From Baseline in SBP, DBP at Week 32 (EOT/ ET) Baseline and Week 32 (end of treatment [EOT]/early termination [ET]) SBP and DBP were measured in a supine position using an automated device preceded by at least 5 minutes of rest for the participant in a quiet setting without any distractions. Baseline value was defined as the most recent measurement prior to the first dose of study treatment after randomization in TP2.
Baseline, Absolute Week 32 Values for Pulse Rate and Change From Baseline in Pulse Rate at Week 32 (EOT/ET) Baseline and Week 32 (EOT/ET) Pulse rate was measured in a supine position using an automated device preceded by at least 5 minutes of rest for the participant in a quiet setting without any distractions. Baseline value was defined as the most recent measurement prior to the first dose of study treatment after randomization in TP2.
Baseline, Absolute Week 32 Values for Temperature and Change From Baseline in Temperature at Week 32 (EOT/ET) Baseline and Week 32 (EOT/ET) Baseline value was defined as the most recent measurement prior to the first dose of study treatment after randomization in TP2.
Baseline, Absolute Week 32 Values for Respiratory Rate and Change From Baseline in Respiratory Rate at Week 32 (EOT/ET) Baseline and Week 32 (EOT/ET) Baseline value was defined as the most recent measurement prior to the first dose of study treatment after randomization in TP2.
Trial Locations
- Locations (72)
Lekarna Pod Platany
🇨🇿Praha, Czechia
Unimed Medical Centre
🇧🇬Plovdiv, Bulgaria
L.K.N. Arthrocentrum, s.r.o.
🇨🇿Hlucin, Czechia
CCR Prague s.r.o.
🇨🇿Praha, Czechia
DCC Sveti Georgi
🇧🇬Plovdiv, Bulgaria
Hospital of Lithuanian University of Health Sciences, Kauno klinikos
🇱🇹Kaunas, Lithuania
X-Medica, s.r.o.
🇨🇿Brno, Czechia
Graves Gilbert Clinic
🇺🇸Bowling Green, Kentucky, United States
Diagnostické centrum Olšanská s.r.o.
🇨🇿Praha, Czechia
Revmatologicky ustav
🇨🇿Praha 2, Czechia
GBUZ "Orenburg Regional Clinical Hospital"
🇷🇺Orenburg, Russian Federation
LLC "Center for Medical Advice and Research-PRACTICE"
🇷🇺Yaroslavl, Russian Federation
Health Center Gradiska
🇧🇦Gradiska, Bosnia and Herzegovina
General Hospital Prim. Dr.Abdulah Nakas
🇧🇦Sarajevo, Bosnia and Herzegovina
Twoja Przychodnia Centrum Medyczne Nowa Sol
🇵🇱Nowa Sol, Poland
IMEDICA s.r.o.
🇨🇿Brno, Czechia
Chirurgie Sibenik
🇨🇿Olomouc, Czechia
Winelands Medical Research Centre
🇿🇦Stellenbosch, Western CAPE, South Africa
University Clinical Center of the Republic of Srpska
🇧🇦Banja Luka, Bosnia and Herzegovina
Lekarna Biovita
🇨🇿Brno, Czechia
SBI of the Ryazan Region "Regional Clinical Cardiology dispensary"
🇷🇺Ryazan, Russian Federation
SBHI of the Republic of Karelia "Republican Hospital n. a. V.A. Baranov"
🇷🇺Petrozavodsk, Russian Federation
Komunalne nekomertsiine pidpryiemstvo "Vinnytska oblasna klinichna likarnia im. M.I. Pyrohova
🇺🇦Vinnytsia, Ukraine
SBI of Ryazan Region "Regional Clinical Hospital"
🇷🇺Ryazan, Russian Federation
FSBEI of HE "Smolensk State Medical University" of the Ministry of Health of the RF
🇷🇺Smolensk, Russian Federation
Prywatna Praktyka Lekarska Prof. UM dr hab. med. Pawel Hrycaj
🇵🇱Poznan, Poland
Gabinet Internistyczno-Reumatologiczny Piotr Adrian Klimiuk
🇵🇱Bialystok, Poland
Małopolskie Badania Kliniczne Sp. z o. o. Sp. k.
🇵🇱Krakow, Poland
Pratia MCM Krakow
🇵🇱Krakow, Poland
NZOZ Lecznica MAK-MED s.c.
🇵🇱Nadarzyn, Poland
Rheuma Medicus Zaklad Opieki Zdrowotnej
🇵🇱Warszawa, Poland
Klaipeda University Hospital
🇱🇹Klaipeda, Lithuania
NZOZ Osteo-Medic s.c. A.Racewicz, J. Supronik
🇵🇱Bialystok, Poland
Zespol Poradni Specjalistycznych REUMED
🇵🇱Lublin, Poland
Institute for Treatment and Rehabilitation Niska Banja
🇷🇸Niska Banja, Serbia
Clinical Center University of Sarajevo
🇧🇦Sarajevo, Bosnia and Herzegovina
Plicni ambulance
🇨🇿Hlucin, Czechia
CTCenter MaVe s.r.o
🇨🇿Olomouc, Czechia
Lekarna Vesalion
🇨🇿Ostrava, Czechia
Lekarna BENU
🇨🇿Pardubice, Czechia
CCR Czech a.s.
🇨🇿Pardubice, Czechia
Lekarna Hradebni s.r.o.
🇨🇿Uherske Hradiste, Czechia
Altoona Center for Clinical Research
🇺🇸Duncansville, Pennsylvania, United States
Rheumatology and Pulmonary Clinic
🇺🇸Beckley, West Virginia, United States
Metroplex Clinical Research Center
🇺🇸Dallas, Texas, United States
UMHAT "Dr Georgi Stranski" EAD
🇧🇬Pleven, Bulgaria
Lekarna Na Lidicke
🇨🇿Brno, Czechia
Revmacentrum MUDr. Mostera, s.r.o.
🇨🇿Brno, Czechia
Lekarna u Pottingea
🇨🇿Olomouc, Czechia
Fakultni Nemocnice v Motole
🇨🇿Praha 5, Czechia
MEDICAL PLUS s.r.o.
🇨🇿Uherske Hradiste, Czechia
Radiodiagnosticka ordinace a pracoviste
🇨🇿Uherske Hradiste, Czechia
Nasz Lekarz Przychodnie Medyczne
🇵🇱Torun, Poland
FGBOU VO "Orenburg State Medical University" of the Ministry of Health of the Russian Federation
🇷🇺Orenburg, Russian Federation
Limited Liability Company Consultative and Diagnostic Rheumatological Center "Healthy Joints"
🇷🇺Novosibirsk, Russian Federation
Limited Liability Company "Clinic on Maroseyka"
🇷🇺Moscow, Russian Federation
FSBEI of HE "Ryazan State Medical University n. a academician I.P.Pavlov"
🇷🇺Ryazan, Russian Federation
Smolensk Regional Clinical Hospital
🇷🇺Smolensk, Russian Federation
LLC "BioMed"
🇷🇺Vladimir, Russian Federation
Institute of Rheumatology
🇷🇸Belgrade, Serbia
Jakaranda Hospital
🇿🇦Pretoria, Gauteng, South Africa
Special Hospital for Rheumatic Diseases Novi Sad
🇷🇸Novi Sad, Serbia
Arthritis Clinical Research Trials
🇿🇦Cape Town, Western CAPE, South Africa
Emmed Research
🇿🇦Pretoria, Gauteng, South Africa
Panorama Medical Centre
🇿🇦Cape Town, Western CAPE, South Africa
Derzhavna ustanova Natsionalnyi naukovyi tsentr Instytut kardiolohii imeni akademika M.D. Strazheska
🇺🇦Kyiv, Ukraine
Medychnyi tsentr tovarystva z obmezhenoiu vidpovidalnistiu " Instytut revmatolohii "
🇺🇦Kyiv, Ukraine
Komunalne Nekomertsiine Pidpryiemstvo "Tsentralna Miska Klinichna Likarnia
🇺🇦M. Ivano-Frankivsk, Ukraine
Komunalne nekomertsiine pidpryiemstvo "Odeska oblasna klinichna likarnia"
🇺🇦Odesa, Ukraine
Komunalne pidpryiemstvo "Likarnia No 1" Zhytomyrskoi miskoi rady
🇺🇦Zhytomyr, Ukraine
Komunalne nekomertsiine pidpryiemstvo Kharkivskoi oblasnoi rady Oblasna klinichna likarnia
🇺🇦Kharkiv, Ukraine
Bahatoprofilnyi medychnyi tsentr Odeskoho natsionalnoho medychnoho universytetu
🇺🇦Odesa, Ukraine