Golimumab (MK-8259 / SCH900259) Treatment Withdrawal in Participants With Non-radiographic Axial Spondyloarthritis (GO-BACK) (MK-8259-038)
- Conditions
- Spondyloarthritis
- Interventions
- Biological: GolimumabBiological: Placebo
- Registration Number
- NCT03253796
- Lead Sponsor
- Merck Sharp & Dohme LLC
- Brief Summary
The purpose of this study is to evaluate the effect of treatment withdrawal compared to continued treatment with golimumab (GLM) administered by subcutaneous (SC) injection on the incidence of a "flare" in non-radiographic axial spondyloarthritis over up to 12 months. The primary hypothesis is that continued treatment with golimumab is superior to treatment withdrawal, based on the percentage of subjects without a "flare" during up to 12 months of blinded therapy.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 323
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Is not of reproductive potential, or is of reproductive potential and agrees to avoid becoming pregnant or impregnating a partner while receiving trial medication or within 6 months after the last dose of trial medication
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Has chronic back pain of ≥3 months duration by history
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Has physician-diagnosed active non-radiographic axial spondyloarthritis (nr-axSpA) with disease duration <= 5 years
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Meets one of the following criteria:
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Has active inflammation on magnetic resonance imaging (MRI) highly suggestive of sacroiliitis associated with spondyloarthropathy and 1 or more of the following spondyloarthritis (SpA) characteristics:
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Inflammatory back pain
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Arthritis (physician-diagnosed)
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Enthesitis (heel) physician-diagnosed (spontaneous pain or tenderness at examination of the site of the insertion of the Achilles tendon or plantar fascia)
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Dactylitis (physician-diagnosed)
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Psoriasis (physician-diagnosed)
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History of physician-diagnosed inflammatory bowel disease (IBD)
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History of uveitis confirmed by an ophthalmologist
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Good response to nonsteroidal anti-inflammatory drugs (NSAID)
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Family history of SpA (presence of ankylosing spondylitis, psoriasis, acute uveitis, reactive arthritis, or IBD)
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Elevated C-reactive protein (CRP)
- Human leukocyte antigen B27 (HLA-B27)+ gene OR
-
-
Has a HLA-B27+ gene and 2 or more of the following SpA characteristics:
- Inflammatory back pain
- Arthritis (physician-diagnosed)
- Enthesitis (heel) physician-diagnosed (spontaneous pain or tenderness at examination of the site of the insertion of the Achilles tendon or plantar fascia)
- Dactylitis (physician-diagnosed)
- Psoriasis (physician-diagnosed)
- History of physician-diagnosed inflammatory bowel disease (IBD)
- History of uveitis confirmed by an ophthalmologist
- Good response to nonsteroidal anti-inflammatory drugs (NSAID)
- Family history of SpA (presence of ankylosing spondylitis, psoriasis, acute uveitis, reactive arthritis, or IBD)
- Elevated C-reactive protein (CRP)
-
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Has elevated CRP at Screening or evidence of active inflammation in the sacroiliac joints on MRI
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Has an Ankylosing Spondylitis Disease Activity Score (ASDAS) >= 2.1 at Screening
-
Shows high disease activity at Screening and Baseline of both a Total Back Pain score of ≥4 and a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score of >= 4
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Has an acceptable history of NSAID use
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Has no history of untreated latent or active tuberculosis (TB) prior to Screening
-
Has had no recent close contact with a person with active TB or, if there has been such contact, will undergo additional evaluations and receive appropriate treatment for latent TB
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Agrees to undergo screening for hepatitis B virus (HBV) and demonstrates negative results for hepatitis B surface antigen (HBsAg) and HBV deoxyribonucleic acid (DNA)
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Has bilateral sacroiliitis Grade 2 or unilateral sacroiliitis Grade 3 or Grade 4 on conventional x-rays
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Is a nursing or pregnant female, or intends to become pregnant within 6 months after receiving trial medication
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Intends to donate eggs (female participants) or sperm (male participants) while receiving trial medication or within 6 months after trial medication
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Has any clinically significant condition or situation that would interfere with the trial evaluations or participation in the trial
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Has ever received any cytotoxic drugs, including chlorambucil, cyclophosphamide, nitrogen mustard, or other alkylating agents
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Has received any treatment listed below more recently than the indicated off-drug period prior to Screening
- • Disease-modifying anti-rheumatic drugs (30 days off drug)
- • Live vaccinations (3 months off drug)
- • Investigational medications (30 days or 5 half-lives off drug, whichever is longer)
- • Bacille Calmette-Guerin (BCG) vaccination (12 months off drug)
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Has any systemic inflammatory condition, including psoriatic arthritis, active Lyme disease, systemic lupus erythematosus, infectious arthritis, vasculitis, parvovirus infection, rheumatoid arthritis, active uveitis, or active IBD
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Has a history of latent or active granulomatous infection prior to Screening
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Had a nontuberculous mycobacterial infection or opportunistic infection within 6 months prior to Screening
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Has a history of an infected joint prosthesis, or has received antibiotics for a suspected infection of a joint prosthesis, if that prosthesis has not been removed or replaced
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Had a serious infection, has been hospitalized for an infection, or has been treated with IV antibiotics for an infection within 2 months prior to Baseline
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Had a history of, or ongoing, chronic or recurrent infectious disease
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Is known to be infected with human immunodeficiency virus (HIV) or seropositive for hepatitis C virus (HCV)
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Has had a chest x-ray within 2 months prior to Screening that shows an abnormality suggestive of a current active infection or malignancy
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Has a history of lymphoproliferative disease
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Has had a malignancy within 5 years before screening (exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of cervix that has been surgically cured)
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Has a history of known demyelinating diseases such as multiple sclerosis or optic neuritis
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Has a history of or concurrent congestive heart failure of any grade
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Has a transplanted organ (with the exception of a corneal transplant performed >= 3 months prior to baseline)
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Has current signs or symptoms of significant medical illness which could interfere with the trial, or require treatment that might interfere with the trial
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Is a user of recreational or illicit drugs or has or had a substance abuse (drug or alcohol) problem within the previous 2 years
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description GLM SC Q2M (Reduced Treatment Regimen) Placebo Period 1: participants are treated with OL GLM SC QM for up to 10 months; Period 2: participants are treated with double-blinded GLM SC every other month alternating with matching placebo to GLM every other month for up to 12 months GLM SC Q2M (Reduced Treatment Regimen) Golimumab Period 1: participants are treated with OL GLM SC QM for up to 10 months; Period 2: participants are treated with double-blinded GLM SC every other month alternating with matching placebo to GLM every other month for up to 12 months GLM SC QM (Full Treatment Regimen) Golimumab Period 1: participants are treated with open-label (OL) GLM SC QM for up to 10 months; Period 2: participants are treated with double-blinded SC GLM QM for up to 12 months Placebo (Treatment Withdrawal Regimen) Golimumab Period 1: participants are treated with OL GLM SC QM for up to 10 months; Period 2: participants are treated with double-blinded placebo for up to 12 months Placebo (Treatment Withdrawal Regimen) Placebo Period 1: participants are treated with OL GLM SC QM for up to 10 months; Period 2: participants are treated with double-blinded placebo for up to 12 months OL GLM Retreatment Golimumab Participants who experience a disease flare during double-blinded treatment in Period 2 will discontinue blinded treatment and receive OL GLM SC QM.
- Primary Outcome Measures
Name Time Method Percentage of Participants Without a Disease Activity Flare During Period 2 Up to 12 months Disease flare is defined as an Ankylosing Spondylitis Disease Activity Score (ASDAS) at two consecutive visits that both show either absolute score ≥2.1 or a post-withdrawal increase of ≥1.1 relative to baseline prior to the first dose of double-blind treatment in Period 2. The ASDAS is a composite index assessing disease activity in axial spondyloarthropathies that consists of 4 self-assessed parameters and 1 laboratory parameter. The self-assessed parameters of back pain, duration of morning stiffness, Patient Global Disease Assessment (PGDn), and peripheral pain/swelling are individually scored on a numeric scale of 0 to 10, with 0 being low activity/impact and 10 being high activity/impact. The self-assessed criteria and the laboratory value of CRP are combined to provide the total ASDAS score, which has a lower limit of 0.6 and no defined upper limit. A higher score indicates greater disease activity.
- Secondary Outcome Measures
Name Time Method Time to First Disease Flare Month 3, Month 6, Month 9, and Month 12 The Kaplan-Meier analysis of time to first "flare" in Period 2 is represented by the percentage of participants who experienced a disease flare relative to baseline prior to the first dose of double-blind treatment in Period 2. Disease flare is defined as ASDAS at two consecutive visits that both show either absolute score ≥2.1 or a post-withdrawal increase of ≥1.1.
Percentage of Participants Achieving ASAS20 Response (Open-label Retreatment) Up to 12 months ASAS20 is a 20% improvement in response (per the Assessment in Ankylosing Spondylitis International Working Group) defined as meeting 2 criteria: 1) An improvement of ≥20% from Baseline and an absolute improvement from Baseline of ≥1.0 in at least 3 of 4 domains, and 2) Absence of deterioration from Baseline (defined as a ≥20% worsening and an absolute worsening of ≥1.0) in the potential remaining domain. Baseline for ASAS20 analysis is defined as the last ASAS score prior to the first dose of open-label retreatment in Period 2. The ASAS consists of 4 domains: the Patient Global Disease Assessment (PGDn), total back pain, function (Bath Ankylosing Spondylitis Functional Index \[BASFI\]), and morning stiffness (mean of questions 5 and 6 of Bath Ankylosing Spondylitis Disease Activity Index \[BASDAI\]). Each domain is measured on a 10-point numeric scale from 0=no disease symptoms/impact to 10=extreme disease symptoms/impact, with a higher score indicating more severe impairment.
Percentage of Participants Achieving ASAS Partial Remission (Double-blind Treatment) Up to 12 months ASAS partial remission is defined as a score of ≤2 in all 4 ASAS domains. Baseline for this analysis is defined as the ASAS score prior to the first dose of double-blind treatment in Period 2. The ASAS consists of 4 domains: Patient Global Disease Assessment (PGDn), total back pain, function (Bath Ankylosing Spondylitis Functional Index \[BASFI\]), and morning stiffness (mean of questions 5 and 6 of Bath Ankylosing Spondylitis Disease Activity Index \[BASDAI\]). Each domain is measured on a 10-point numeric scale from 0=no disease symptoms/impact to 10=extreme disease symptoms/impact, with a higher score indicating more severe impairment.
Percentage of Participants Achieving ASAS20 (Assessment in SpondyloArthritis International Society) Response (Double-blind Treatment) Up to 12 months ASAS20 is a 20% improvement in response (per the Assessment in Ankylosing Spondylitis International Working Group) defined as meeting 2 criteria: 1) An improvement of ≥20% from Baseline and an absolute improvement from Baseline of ≥1.0 in at least 3 of 4 domains, and 2) Absence of deterioration from Baseline (defined as a ≥20% worsening and an absolute worsening of ≥1.0) in the potential remaining domain. Baseline for ASAS20 analysis is defined as the last ASAS score prior to the first dose of double-blind treatment in Period 2. The ASAS consists of 4 domains: the Patient Global Disease Assessment (PGDn), total back pain, function (Bath Ankylosing Spondylitis Functional Index \[BASFI\]), and morning stiffness (mean of questions 5 and 6 of Bath Ankylosing Spondylitis Disease Activity Index \[BASDAI\]). Each domain is measured on a 10-point numeric scale from 0=no disease symptoms/impact to 10=extreme disease symptoms/impact, with a higher score indicating more severe impairment.
Percentage of Participants With a Flare Who Show a Clinical Response Within 3 Months of Open-Label Golimumab Retreatment Up to 3 months following start of retreatment Clinical response is defined as Bath Ankylosing Spondylitis Disease Assessment Index (BASDAI) score improvement of ≥2.0 or ≥50% improvement within 3 months of the start of retreatment, relative to the mean of the two consecutive BASDAI scores that defined the flare. Sustained clinical response refers to participants who attained clinical response and maintained BASDAI criteria throughout the 3-month retreatment period. Response data was collected throughout Period 2 (12 months) and censored to include only the first 3 months after retreatment for a disease flare. The BASDAI is a summary of 6 participant-assessed measures rated on scales of 0 (none) to 10 (very severe): fatigue, spinal pain, joint pain/swelling, tenderness, morning stiffness, and duration of morning stiffness \[0 (zero) to 10 (2 or more hours)\]. The BASDAI score is the mean of responses to the 6 questions with a minimum of 0 and a maximum of 10. A higher score indicates greater disease activity.
Percentage of Participants Achieving ASAS40 Response (Open-label Retreatment) Up to 12 months ASAS40 is a 40% improvement in response (per the Assessment in Ankylosing Spondylitis International Working Group) defined as meeting 2 criteria: 1) An improvement of ≥40% from Baseline and an absolute improvement from Baseline of ≥2.0 in at least 3 of 4 domains, and 2) No deterioration from Baseline in the potential remaining domain. Baseline for ASAS40 analysis is defined as the last ASAS score prior to the first dose of open-label retreatment in Period 2. The ASAS consists of 4 domains: the Patient Global Disease Assessment (PGDn), total back pain, function (Bath Ankylosing Spondylitis Functional Index \[BASFI\]), and morning stiffness (mean of questions 5 and 6 of Bath Ankylosing Spondylitis Disease Activity Index \[BASDAI\]). Each domain is measured on a 10-point numeric scale from 0=no disease symptoms/impact to 10=extreme disease symptoms/impact, with a higher score indicating more severe impairment.
Percentage of Participants Achieving ASAS Partial Remission (Open-label Retreatment) Up to 12 months ASAS partial remission is defined as a score of ≤2 in all 4 ASAS domains. Baseline for this analysis is defined as the ASAS score prior to the first dose of open-label retreatment in Period 2. The ASAS consists of 4 domains: Patient Global Disease Assessment (PGDn), total back pain, function (Bath Ankylosing Spondylitis Functional Index \[BASFI\]), and morning stiffness (mean of questions 5 and 6 of Bath Ankylosing Spondylitis Disease Activity Index \[BASDAI\]). Each domain is measured on a 10-point numeric scale from 0=no disease symptoms/impact to 10=extreme disease symptoms/impact, with a higher score indicating more severe impairment.
Percentage of Participants Achieving ASAS40 Response (Double-blind Treatment) Up to 12 months ASAS40 is a 40% improvement in response (per the Assessment in Ankylosing Spondylitis International Working Group) defined as meeting 2 criteria: 1) An improvement of ≥40% from Baseline and an absolute improvement from Baseline of ≥2.0 in at least 3 of 4 domains, and 2) No deterioration from Baseline in the potential remaining domain. Baseline for ASAS40 analysis is defined as the last ASAS score prior to the first dose of double-blind treatment in Period 2. The ASAS consists of 4 domains: the Patient Global Disease Assessment (PGDn), total back pain, function (Bath Ankylosing Spondylitis Functional Index \[BASFI\]), and morning stiffness (mean of questions 5 and 6 of Bath Ankylosing Spondylitis Disease Activity Index \[BASDAI\]). Each domain is measured on a 10-point numeric scale from 0=no disease symptoms/impact to 10=extreme disease symptoms/impact, with a higher score indicating more severe impairment.
Percentage of Participants Achieving Inactive Disease Status (Double-Blind Treatment) Up to 12 months Inactive disease status is defined as an ASDAS score \<1.3. The ASDAS is a composite index assessing disease activity in axial spondyloarthropathies that consists of 4 self-assessed parameters and 1 laboratory parameter. The self-assessed parameters of back pain, duration of morning stiffness, Patient Global Disease Assessment (PGDn), and peripheral pain/swelling are individually scored on a numeric scale of 0 to 10, with 0 being low activity/impact and 10 being high activity/impact. The self-assessed criteria and the laboratory value of CRP are combined to provide the total ASDAS score, which has a lower limit of 0.6 and no defined upper limit. A higher score indicates greater disease activity.
Percentage of Participants Who Experienced an Adverse Event (AE) in Period 2 Up to approximately 15 months This endpoint evaluated the safety and tolerability of withdrawing from or continuing treatment with golimumab in Period 2. An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant administered a study treatment and which does not necessarily have to have a causal relationship with this treatment. An AE could be any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a study treatment, whether or not considered related to the study treatment. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of study treatment, is also an AE. The analysis includes AEs that occurred through 90 days after the last dose of study treatment.
Percentage of Participants Achieving BASDAI50 Response (Double-blind Treatment) Up to 12 months BASDAI50 is defined as ≥50% improvement from baseline in the Bath Ankylosing Spondylitis Disease Assessment Index (BASDAI) score. Baseline for BASDAI50 analysis is defined as the last BASDAI score prior to the first dose of double-blind treatment in Period 2. The BASDAI is a summary of 6 participant-assessed measures rated on scales of 0 (none) to 10 (very severe): fatigue, spinal pain, joint pain/swelling, tenderness, morning stiffness, and duration of morning stiffness \[0 (zero) to 10 (2 or more hours)\]. The BASDAI score is the mean of responses to the 6 questions with a minimum of 0 and a maximum of 10. A higher score indicates greater disease activity.
Percentage of Participants Achieving Inactive Disease Status (Open-label Retreatment) Up to 12 months Inactive disease status is defined as an ASDAS score \<1.3. The ASDAS is a composite index assessing disease activity in axial spondyloarthropathies that consists of 4 self-assessed parameters and 1 laboratory parameter. The self-assessed parameters of back pain, duration of morning stiffness, Patient Global Disease Assessment (PGDn), and peripheral pain/swelling are individually scored on a numeric scale of 0 to 10, with 0 being low activity/impact and 10 being high activity/impact. The self-assessed criteria and the laboratory value of CRP are combined to provide the total ASDAS score, which has a lower limit of 0.6 and no defined upper limit. A higher score indicates greater disease activity.
Percentage of Participants Who Discontinued Study Treatment Due to an AE in Period 2 Up to approximately 12 months This endpoint evaluated the safety and tolerability of withdrawing from or continuing treatment with golimumab in Period 2. An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant administered a study treatment and which does not necessarily have to have a causal relationship with this treatment. An AE could be any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a study treatment, whether or not considered related to the study treatment. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of study treatment, is also an AE.
Percentage of Participants Achieving BASDAI50 Response (Open-label Retreatment) Up to 12 months BASDAI50 is defined as ≥50% improvement from baseline in the Bath Ankylosing Spondylitis Disease Assessment Index (BASDAI) score. Baseline for BASDAI50 analysis is defined as the last BASDAI score prior to the first dose of open-label retreatment in Period 2. The BASDAI is a summary of 6 participant-assessed measures rated on scales of 0 (none) to 10 (very severe): fatigue, spinal pain, joint pain/swelling, tenderness, morning stiffness, and duration of morning stiffness \[0 (zero) to 10 (2 or more hours)\]. The BASDAI score is the mean of responses to the 6 questions with a minimum of 0 and a maximum of 10. A higher score indicates greater disease activity.
Trial Locations
- Locations (71)
CCBR Ostrava s.r.o. ( Site 0001)
🇨🇿Ostrava, Czechia
FN Brno ( Site 0005)
🇨🇿Brno, Czechia
Spitalul Clinic Sfanta Maria ( Site 0182)
🇷🇴Bucharest, Romania
GUZ Regional Clinical Hospital ( Site 0076)
🇷🇺Saratov, Oktyabrskiy Region, Russian Federation
SBHI Leningrad Regional Clinical Hospital ( Site 0065)
🇷🇺Saint Petersburg, Russian Federation
SPb SBHI Clinical Rheumatological Hospital 25 ( Site 0077)
🇷🇺Saint Petersburg, Russian Federation
Hacettepe Universitesi Tip Fakultesi Hastanesi ( Site 0091)
🇹🇷Ankara, Turkey
NZOZ Reumed ( Site 0051)
🇵🇱Lublin, Poland
Covamed Serv SRL ( Site 0178)
🇷🇴Sfantu Gheorghe, Romania
Akdeniz Universitesi Tip Fakultesi Romatoloji Departmani ( Site 0094)
🇹🇷Antalya, Ankara, Turkey
Ankara Numune Egitim Arastirma Hastanesi ( Site 0092)
🇹🇷Ankara, Turkey
Kyivska miska klinichna likarnia N3 ( Site 0266)
🇺🇦Kyiv, Ukraine
M.V.Sklifosovskyi Poltava Regional Clinical Hospital ( Site 0224)
🇺🇦Poltava, Ukraine
Medical Plus s.r.o ( Site 0010)
🇨🇿Uherske Hradiste, Czechia
Artroscan s.r.o. ( Site 0007)
🇨🇿Ostrava-Trebovice, Czechia
Revmatologie s.r.o. ( Site 0009)
🇨🇿Brno, Czechia
CCR Czech a.s. ( Site 0003)
🇨🇿Pardubice, Czechia
Fakultni nemocnice v Motole ( Site 0127)
🇨🇿Praha, Czechia
CCR Prague s.r.o ( Site 0004)
🇨🇿Praha, Czechia
Universitaetsklinik der Charite Berlin ( Site 0023)
🇩🇪Berlin, Germany
U. klinikum Koeln AOER ( Site 0025)
🇩🇪Koeln, Germany
Rheumazentrum Ruhrgebiet ( Site 0021)
🇩🇪Herne, Germany
Antonius Ziekenhuis Sneek ( Site 0043)
🇳🇱Sneek, Friesland, Netherlands
Klinikum der Universitaet Muenchen - LMU ( Site 0026)
🇩🇪Muenchen, Germany
Herbert Kellner Innere Medizin Rheumatologie und Gastroenterologie ( Site 0022)
🇩🇪Muenchen, Germany
Vrij Universiteit Medisch Centrum ( Site 0044)
🇳🇱Amsterdam, Netherlands
Maasstad Ziekenhuis ( Site 0042)
🇳🇱Rotterdam, Netherlands
Leids Universitair Medisch Centrum ( Site 0041)
🇳🇱Leiden, Netherlands
Centrum Medyczne Pratia Katowice ( Site 0059)
🇵🇱Katowice, Slaskie, Poland
Prywatna Praktyka Lekarska, Dr. med. Pawel Hrycaj ( Site 0060)
🇵🇱Poznan, Wielkopolskie, Poland
Klinika Reumatologii i Ukladowych Chorob Tkanki Lacznej ( Site 0153)
🇵🇱Bydgoszcz, Poland
NZOZ Osteo-Medic s.c. A. Racewicz, R. Supronik ( Site 0058)
🇵🇱Bialystok, Poland
Centrum Kliniczno-Badawcze ( Site 0152)
🇵🇱Elblag, Poland
Krakow Medical Centre ( Site 0052)
🇵🇱Krakow, Poland
Lubelskie Centrum Diagnostyczne ( Site 0053)
🇵🇱Swidnik, Poland
Pomorskie Cent. Reumatologiczne IM.Dr. Titz-Kosko W Sopocie Sp. Z.o.o. ( Site 0057)
🇵🇱Sopot, Poland
NZOZ Nasz Lekarz Praktyka Grupowa Lekarzy Rodzinnych ( Site 0151)
🇵🇱Torun, Poland
Reumatika ( Site 0055)
🇵🇱Warszawa, Poland
Centrul Medical de Diagnostic si Tratament Ambulator Neomed ( Site 0177)
🇷🇴Brasov, Romania
Clinical Hospital Ioan Cantacuzino ( Site 0184)
🇷🇴Bucaresti, Romania
Colentina Clinical Hospital ( Site 0231)
🇷🇴Bucarest, Romania
SC Duo Medical SRL ( Site 0183)
🇷🇴Bucuresti, Romania
Spitalul Clinic Judetean de Urgenta Cluj-Napoca ( Site 0176)
🇷🇴Cluj Napoca, Romania
S.C.Pelican Impex S.R.L ( Site 0232)
🇷🇴Oradea, Romania
RKMed Center ( Site 0180)
🇷🇴Iasi, Romania
Cabinet Medical Medicina Interna Dr. Triff Carina ( Site 0179)
🇷🇴Timisoara, Romania
Rheumatology Research Institute n.a. V.A.Nasonova of RAMS ( Site 0061)
🇷🇺Moscow, Russian Federation
Yaroslavl Clinical Hospital for Emergency Care na. NV. Solovyev. ( Site 0075)
🇷🇺Yaroslavl, Russian Federation
LLC Sanavita ( Site 0074)
🇷🇺Saint-Petersburg, Russian Federation
Tolyatti City Clinical Hospital 5 ( Site 0069)
🇷🇺Tolyatti, Russian Federation
Hospital Universitario Reina Sofia ( Site 0081)
🇪🇸Cordoba, Spain
Hospital de Basurto ( Site 0082)
🇪🇸Bilbao, Spain
Hospital Clinico Universitario Virgen de la Arrixaca ( Site 0085)
🇪🇸Murcia, Spain
Hospital Universitario La Paz ( Site 0083)
🇪🇸Madrid, Spain
Ankara Universitesi Tıp Fakultesi ( Site 0093)
🇹🇷Ankara, Turkey
Pamukkale Unv. Tip Fak. ( Site 0097)
🇹🇷Denizli, Turkey
Marmara Universitesi Pendik Egitim ve Arastirma Hastanesi ( Site 0098)
🇹🇷Istanbul, Turkey
Kocaeli Universitesi Tip Fakultesi Ic Hastaliklari ( Site 0096)
🇹🇷Kocaeli, Turkey
Cherkassy Regional hospital of Cherkassy Regional council ( Site 0221)
🇺🇦Cherkassy, Ukraine
MI Dnipr Regional Clinical Hospital named after I.I. Mechnikov ( Site 0222)
🇺🇦Dnipropetrovsk, Ukraine
SI National Institute of therapy n.a L.T. Maloi NAMS of Ukraine ( Site 0261)
🇺🇦Kharkiv, Ukraine
M. D. Strazhesko Institute of Cardiology. ( Site 0264)
🇺🇦Kyiv, Ukraine
Clinic of Modern Rheumatology ( Site 0265)
🇺🇦Kyiv, Ukraine
Communal City Clinical Hospital #4 ( Site 0230)
🇺🇦Lviv, Ukraine
Medical Center Ibn Sina ( Site 0268)
🇺🇦Kyiv, Ukraine
MI Odesa Regional Clinical Hospital ( Site 0226)
🇺🇦Odesa, Ukraine
Vinnitsa Regional Clinical Hospital n.a. Pirogov ( Site 0225)
🇺🇦Vinnutsya, Ukraine
SRI of Invalid Rehabilitation of Vinnytsia M.I.Pyrogov ( Site 0263)
🇺🇦Vinnytsia, Ukraine
Zaporizhzha Regional Clinical Hospital ( Site 0223)
🇺🇦Zaporizhzhya, Ukraine
PV - Medical s.r.o. ( Site 0006)
🇨🇿Zlin, Czechia
ME of Health Care Kharkiv City Clinical Hospital #8 ( Site 0262)
🇺🇦Kharkiv, Ukraine