Efficacy and Safety of Vedolizumab Subcutaneously (SC) as Maintenance Therapy in Ulcerative Colitis
- Conditions
- Colitis, Ulcerative
- Interventions
- Registration Number
- NCT02611830
- Lead Sponsor
- Takeda
- Brief Summary
The purpose of this study is to assess the effect of vedolizumab subcutaneous (vedolizumab SC) maintenance treatment on clinical remission at Week 52 in participants with moderately to severely active ulcerative colitis (UC) who achieved clinical response following administration of vedolizumab intravenous (vedolizumab IV) induction therapy.
- Detailed Description
The drug being tested in this study is called vedolizumab subcutaneous (vedolizumab SC). Vedolizumab SC is being tested to treat people who have moderate to severely active ulcerative colitis. This study will look at clinical remission as well as mucosal healing, durable clinical response, durable clinical remission, and corticosteroid free remission in participants with UC who receive vedolizumab SC maintenance therapy after having achieved a clinical response to vedolizumab IV induction therapy.
The study enrolled 383 patients. All participants will enter into a 6-week Induction Phase where they will be administered open-label vedolizumab IV 300 mg via intravenous infusion (IV) at Week 0 (Day 1) and Week 2 (Day 15), and will then be assessed for a clinical response at Week 6. Participants who achieve a clinical response at Week 6 will be randomly assigned to one of the three treatment groups:
Vedolizumab SC 108 mg Q2W and Placebo IV Q8W Vedolizumab IV 300 mg Q8W and Placebo SC Q2W Placebo SC Q2W and Placebo IV Q8W
Participants who do not achieve a clinical response at Week 6 will not be randomized in to the Maintenance Period, and will receive a third infusion of vedolizumab IV 300 mg at Week 6.
This multi-center trial will be conducted worldwide. The overall time to participate in this study is up to 71 weeks (up to 4 weeks of screening, 52 weeks of treatment and 18 weeks of safety follow-up). Participants will make multiple visits to the clinic, plus a final visit 18 weeks after last dose of study drug for a follow-up assessment. Participants will also participate in a long-term safety follow-up, by phone, at 6 months after the last dose of study drug.
After the Week 52 assessments, participants meeting protocol-defined criteria were eligible to enroll in Study MLN0002SC-3030 (NCT02620046; Long-term Safety) to receive open-label vedolizumab treatment. Participants who withdrew early (prior to Week 52) due to sustained nonresponse, disease worsening, or the need for rescue medications may also have been eligible for Study MLN0002SC-3030. Participants who did not enroll into Study MLN0002SC-3030 were to complete a final on-study safety assessment at Week 68 (or final safety visit 18 weeks after the last dose) in the Maintenance Phase of Study MLN0002SC-3027.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 383
- Diagnosis of ulcerative colitis (UC) established at least 6 months prior to screening, by clinical and endoscopic evidence and corroborated by a histopathology report.
- Moderately to severely active UC as determined by a complete Mayo score of 6-12 (with an endoscopic subscore ≥2)
- Evidence of UC extending proximal to the rectum (≥15 cm of involved colon).
- Inadequate response with, loss of response to, or intolerance to corticosteroids, immunomodulators, or Tumor Necrosis Factor-alpha (TNF-α) antagonists
- Evidence of abdominal abscess or toxic megacolon at the initial Screening Visit.
- Extensive colonic resection, subtotal or total colectomy.
- Ileostomy, colostomy, or known fixed symptomatic stenosis of the intestine.
- Prior exposure to investigational or approved non-biologic therapies (eg, cyclosporine, tacrolimus, thalidomide, methotrexate or tofacitinib) for the treatment of underlying disease within 30 days or 5 half-lives of screening (whichever is longer).
- Prior exposure to any investigational or approved biologic or biosimilar agent within 60 days or 5 half-lives of screening (whichever is longer).
- Prior exposure to vedolizumab
- Surgical intervention for UC required at any time during the study.
- History or evidence of adenomatous colonic polyps that have not been removed or has a history or evidence of colonic mucosal dysplasia.
- Suspected or confirmed diagnosis of Crohn's entercolitis, indeterminate colitis, ischaemic colitis, radiation colitis, diverticular disease associated with colitis, or microscopic colitis.
- Active infections
- Chronic hepatitis B virus (HBV) infection or chronic hepatitis C virus (HCV) infection, HIV or tuberculosis (active or latent), identified congenital or acquired immunodeficiency. HBV immune participants (ie, being hepatitis B surface antigen [HBsAg] negative and hepatitis B antibody positive) may, however, be included.
- History of any major neurological disorders, including stroke, multiple sclerosis, brain tumor, demyelinating or neurodegenerative disease.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Maintenance Phase: Induction IV + Vedolizumab 108 mg SC Placebo IV Participants received vedolizumab 300 mg IV infusion in open-label induction phase and achieved clinical response at Week 6 were randomized to receive vedolizumab SC in maintenance phase. Vedolizumab SC, 108 mg, injection, Q2W and placebo-matching IV infusions, Q8W, starting at Week 6 up to approximately Week 50. Maintenance Phase: Induction IV + Placebo Placebo IV Participants received vedolizumab 300 mg IV infusion in open-label induction phase and achieved clinical response at Week 6 were randomized to receive placebo in maintenance phase. Placebo-matching subcutaneous (SC) injections, once every 2 weeks (Q2W) and placebo-matching IV infusions, once every 8 weeks (Q8W) starting at Week 6 up to approximately Week 50. Maintenance Phase: Induction IV + Vedolizumab 300 mg IV Placebo SC Participants received vedolizumab 300 mg IV infusion in open-label induction phase and achieved clinical response at Week 6 were randomized to receive vedolizumab IV in maintenance phase. Vedolizumab 300 mg, IV infusion, Q8W and placebo-matching SC injection, Q2W starting at Week 6 up to approximately Week 50. Maintenance Phase: Induction IV + Placebo Placebo SC Participants received vedolizumab 300 mg IV infusion in open-label induction phase and achieved clinical response at Week 6 were randomized to receive placebo in maintenance phase. Placebo-matching subcutaneous (SC) injections, once every 2 weeks (Q2W) and placebo-matching IV infusions, once every 8 weeks (Q8W) starting at Week 6 up to approximately Week 50. Maintenance Phase: Induction IV + Placebo Vedolizumab 300 mg IV Participants received vedolizumab 300 mg IV infusion in open-label induction phase and achieved clinical response at Week 6 were randomized to receive placebo in maintenance phase. Placebo-matching subcutaneous (SC) injections, once every 2 weeks (Q2W) and placebo-matching IV infusions, once every 8 weeks (Q8W) starting at Week 6 up to approximately Week 50. Maintenance Phase: Induction IV + Vedolizumab 300 mg IV Vedolizumab 300 mg IV Participants received vedolizumab 300 mg IV infusion in open-label induction phase and achieved clinical response at Week 6 were randomized to receive vedolizumab IV in maintenance phase. Vedolizumab 300 mg, IV infusion, Q8W and placebo-matching SC injection, Q2W starting at Week 6 up to approximately Week 50. Maintenance Phase: Induction IV + Vedolizumab 108 mg SC Vedolizumab 300 mg IV Participants received vedolizumab 300 mg IV infusion in open-label induction phase and achieved clinical response at Week 6 were randomized to receive vedolizumab SC in maintenance phase. Vedolizumab SC, 108 mg, injection, Q2W and placebo-matching IV infusions, Q8W, starting at Week 6 up to approximately Week 50. Maintenance Phase: Induction IV + Vedolizumab 108 mg SC Vedolizumab 108 mg SC Participants received vedolizumab 300 mg IV infusion in open-label induction phase and achieved clinical response at Week 6 were randomized to receive vedolizumab SC in maintenance phase. Vedolizumab SC, 108 mg, injection, Q2W and placebo-matching IV infusions, Q8W, starting at Week 6 up to approximately Week 50.
- Primary Outcome Measures
Name Time Method Percentage of Participants Achieving Clinical Remission at Week 52 Week 52 Clinical remission is defined as a complete Mayo score ≤ 2 points and no individual subscore \> 1 point. The Mayo score is a standard assessment tool to measure ulcerative colitis disease activity in clinical trials. The index consists of 4 subscores: rectal bleeding, stool frequency, findings on endoscopy, and physician's global assessment. Each subscore is scored on a scale from 0 to 3 and the complete Mayo score ranges from 0 to 12 (higher scores indicate greater disease activity).
- Secondary Outcome Measures
Name Time Method Percentage of Participants Achieving Mucosal Healing at Week 52 Week 52 Mucosal healing is defined as Mayo endoscopic subscore ≤1 point. The findings on endoscopy scale ranges from 0 to 3, where 0=normal or inactive disease 1=mild disease (erythema, decreased vascular pattern, mild friability) 2=moderate disease (marked erythema, lack of vascular pattern, friability, erosions) 3=severe disease (spontaneous bleeding, ulceration).
Percentage of Participants Achieving Durable Clinical Response at Week 6 and Week 52 Baseline, Weeks 6 and 52 Durable clinical response is defined as clinical response at both Weeks 6 and 52, where clinical response is defined as a reduction in complete Mayo score of ≥3 points and ≥30% from Baseline (Week 0) with an accompanying decrease in rectal bleeding subscore of ≥1 point or absolute rectal bleeding subscore of ≤1 point. The Mayo score is a standard assessment tool to measure ulcerative colitis disease activity in clinical trials. The index consists of 4 subscores: rectal bleeding, stool frequency, findings on endoscopy, and physician's global assessment. Each subscore is scored on a scale from 0 to 3 and the complete Mayo score ranges from 0 to 12 (higher scores indicate greater disease activity).
Percentage of Participants Achieving Durable Clinical Remission at Week 6 and Week 52 Weeks 6 and 52 Durable clinical remission is defined as clinical remission at both Weeks 6 and 52. Clinical remission is defined as a complete Mayo score of less than or equal to (≤) 2 points and no individual subscore greater than (\>) 1 point. The Mayo score is a standard assessment tool to measure ulcerative colitis disease activity in clinical trials. The index consists of 4 subscores: rectal bleeding, stool frequency, findings on endoscopy, and physician's global assessment. Each subscore is scored on a scale from 0 to 3 and the complete Mayo score ranges from 0 to 12 (higher scores indicate greater disease activity).
Percentage of Participants Achieving Corticosteroid-free Remission at Week 52 Week 52 Corticosteroid-free remission is defined as participants using oral corticosteroids at Baseline (Week 0) who have discontinued oral corticosteroids and are in clinical remission at Week 52. Clinical remission is defined as a complete Mayo score of ≤ 2 points and no individual subscore \> 1 point. The Mayo score is a standard assessment tool to measure ulcerative colitis disease activity in clinical trials. The index consists of 4 subscores: rectal bleeding, stool frequency, findings on endoscopy, and physician's global assessment. Each subscore is scored on a scale from 0 to 3 and the complete Mayo score ranges from 0 to 12 (higher scores indicate greater disease activity).
Trial Locations
- Locations (154)
SI Divisional Clinical Hospital of Uzhgorod Station of ST&BA LZ Dep of Therapy SHEI Uzhgorod NU
🇺🇦Uzhgorod, Ukraine
Private Small Enterprise Medical Center Pulse
🇺🇦Vinnytsia, Ukraine
Odense Universitetshospital
🇩🇰Odense C, Denmark
L & L Research Choices, Inc.
🇺🇸Miami, Florida, United States
Vanderbilt University Medical Center
🇺🇸Nashville, Tennessee, United States
Florida Center for Gastroenterology
🇺🇸Largo, Florida, United States
Expertia S.A- Mautalen Salud e Investigacion
🇦🇷Ciudad Autonoma Buenos Aires, Argentina
Gastroenterology Group of Naples
🇺🇸Naples, Florida, United States
Gastroenterology Associates of Central Georgia
🇺🇸Macon, Georgia, United States
Research Concierge, LLC
🇺🇸Owensboro, Kentucky, United States
Atlanta Gastroenterology Associates
🇺🇸Atlanta, Georgia, United States
Long Island Clinical Research Associates
🇺🇸Great Neck, New York, United States
Cotton-O'Neil Clinical Research Center, Digestive Health
🇺🇸Topeka, Kansas, United States
Clinical Research Institute of Michigan, LLC
🇺🇸Chesterfield, Michigan, United States
Royal Adelaide Hospital
🇦🇺Adelaide, South Australia, Australia
Metropolitan Gastroenterology Group, PC, Chevy Chase Clinical Research
🇺🇸Chevy Chase, Maryland, United States
Options Health Research
🇺🇸Tulsa, Oklahoma, United States
Ehrhardt Clinical Research, LLC
🇺🇸Belton, Missouri, United States
University Clinical Centre of the Republic of Srpska
🇧🇦Banja Luka, Bosnia and Herzegovina
Gastroenterology Associates of Tidewater
🇺🇸Chesapeake, Virginia, United States
Clinique Saint-Pierre
🇧🇪Ottignies, Belgium
Princess Alexandra Hospital
🇦🇺Woolloongabba, Queensland, Australia
MHAT - Silistra AD
🇧🇬Silistra, Bulgaria
AZ Delta
🇧🇪Roeselare, Belgium
MHAT 'Avis Medica' OOD
🇧🇬Pleven, Bulgaria
Axon Clinical, s.r.o.
🇨🇿Praha 8, Czechia
Second MHAT - Sofia AD
🇧🇬Sofia, Bulgaria
Medical Center "Nov Rehabilitatsionen Tsentar", EOOD
🇧🇬Stara Zagora, Bulgaria
LHSC - Victoria Hospital
🇨🇦London, Ontario, Canada
Clinical Hospital Centre Zagreb
🇭🇷Zagreb, Croatia
Ccbr-Synarc A/S
🇨🇿Praha 3, Czechia
A-SHINE s.r.o.
🇨🇿Plzen, Czechia
Krankenhaus Waldfriede e. V.
🇩🇪Berlin, Germany
Fejer Megyei Szent Gyorgy Egyetemi Oktato Korhaz
🇭🇺Szekesfehervar, Hungary
Morales Vargas Centro de Investigacion, S.C.
🇲🇽Leon, Guanajuato, Mexico
Policlinico Universitario Agostino Gemelli
🇮🇹Roma, Italy
Kangbuk Samsung Hospital
🇰🇷Seoul, Korea, Republic of
Karolina Korhaz-Rendelointezet
🇭🇺Mosonmagyarovar, Hungary
Christus Muguerza Sur S.A. de C.V.
🇲🇽Monterrey, Nuevo Leon, Mexico
Sociedad de Metabolismo y Corazon S.C
🇲🇽Veracruz, Mexico
Academisch Medisch Centrum
🇳🇱Amsterdam, Netherlands
Maastricht University Medical Center
🇳🇱Maastricht, Netherlands
Azienda Socio Sanitaria Territoriale Fatebenefratelli (Presidio Ospedale Sacco)
🇮🇹Milano, Italy
Kyungpook National University Hospital
🇰🇷Daegu, Korea, Republic of
BHI of Omsk region Clinical Oncology Dispensary
🇷🇺Omsk, Russian Federation
Istituto Clinico Humanitas
🇮🇹Rozzano, Milano, Italy
Azienda Ospedaliera di Padova
🇮🇹Padova, Italy
Azienda Ospedaliera San Camillo Forlanini
🇮🇹Roma, Italy
Klaipeda Republican Hospital, Public Institution
🇱🇹Klaipeda, Lithuania
FSBIH "Central Clinical Hospital of Russian Academy of Sciences"
🇷🇺Moscow, Russian Federation
NZOZ Vitamed
🇵🇱Bydgoszcz, Poland
SBEI HPE "Rostov State Medical University" of the MoH of the RF
🇷🇺Rostov-on-Don, Russian Federation
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Kyung Hee University Hospital
🇰🇷Seoul, Korea, Republic of
LLC "RIAT SPb"
🇷🇺Saint-Petersburg, Russian Federation
iBiomed Guadalajara
🇲🇽Zapopan, Jalisco, Mexico
Centrum Zdrowia Matki, Dziecka i Mlodziezy
🇵🇱Warszawa, Poland
LexMedica Osrodek Badan Klinicznych
🇵🇱Wroclaw, Poland
Instituto de Investigaciones Aplicadas a la Neurociencia A.C.
🇲🇽Durango, Mexico
GASTROMED Sp. z o.o.
🇵🇱Lublin, Poland
Regional CH Dep of Gastroenterology SHEI Ivano-Frankivsk NMU
🇺🇦Ivano-Frankivsk, Ukraine
Royal Devon and Exeter Hospital (Wonford)
🇬🇧Exeter, Devon, United Kingdom
SI Institute of Gastroenterology of NAMSU Dept of Stomach & Duodenum Diseases, D&ThN SI DMA of MoHU
🇺🇦Dnipro, Ukraine
Complejo Hospitalario de Pontevedra
🇪🇸Pontevedra, Spain
Danderyds Sjukhus AB
🇸🇪Stockholm, Sweden
Clinical Center Zemun
🇷🇸Belgrade, Serbia
KM Management spol. s r.o.
🇸🇰Nitra, Slovakia
CHI Prof.O.O.Shalimov Kharkiv City Clinical Hospital #2
🇺🇦Kharkiv, Ukraine
Ankara University Medical Faculty
🇹🇷Ankara, Turkey
Acibadem Fulya Hospital
🇹🇷Istanbul, Turkey
Univerzitna nemocnica Bratislava, Nemocnica Ruzinov
🇸🇰Bratislava, Slovakia
CI A.and O. Tropiny City Clinical Hospital
🇺🇦Kherson, Ukraine
Karolinska Universitetssjukhuset - Solna
🇸🇪Stockholm, Sweden
Hospital Universitario Puerta de Hierro Majadahonda
🇪🇸Majadahonda, Madrid, Spain
Royal Free Hospital
🇬🇧London, Greater London, United Kingdom
CI Odesa Regional Clinical Hospital
🇺🇦Odesa, Ukraine
MI of Healthcare Kyiv RCH P.L. Shupyk NMA of PGE
🇺🇦Kyiv, Ukraine
SI Branch CH of Zaporizhzhia Station-2 of SE Prydniprovska Railway Dept of Surgery Zaporizhzhia SMU
🇺🇦Zaporizhzhia, Ukraine
UNESP - Faculdade de Medicina da Universidade Estadual Paulista - Campus Botucatu
🇧🇷Botucatu, Sao Paulo, Brazil
HUCFF-UFRJ - Hospital Universitario Clementino Fraga Filho - Universidade Federal do Rio de Janeiro
🇧🇷Rio de Janeiro, Rio Do Janeiro, Brazil
SPb SBIH "City Hospital of Saint Martyr Elizaveta"
🇷🇺St. Petersburg, Russian Federation
FSBI "Scientific Research Institute of Physyology and Basic Medicine" under the SB of RAMS
🇷🇺Novosibirsk, Russian Federation
SBEIHPE Novosibirsk State Medical University
🇷🇺Novosibirsk, Russian Federation
Wolfson Medical Center
🇮🇱Holon, Israel
Chaim Sheba Medical Center
🇮🇱Ramat Gan, Israel
Faculdade de Medicina do ABC
🇧🇷Santo Andre, Sao Paulo, Brazil
Arkansas Primary Care Clinic, PA
🇺🇸Little Rock, Arkansas, United States
Rocky Mountain Clinical Research, LLC
🇺🇸Wheat Ridge, Colorado, United States
Middlesex Gastroenterology Associates
🇺🇸Middletown, Connecticut, United States
Nature Coast Clinical Research, LLC
🇺🇸Inverness, Florida, United States
Shafran Gastroenterology Center
🇺🇸Winter Park, Florida, United States
Gastroenterology Associates, LLC
🇺🇸Baton Rouge, Louisiana, United States
Gastroenterology Associates of Western Michigan, P.L.C.
🇺🇸Wyoming, Michigan, United States
Premier Medical Group of the Hudson Valley, PC
🇺🇸Poughkeepsie, New York, United States
Dayton Gastroenterology, Inc
🇺🇸Dayton, Ohio, United States
Virginia Mason Seattle Main Clinic
🇺🇸Seattle, Washington, United States
Concord Repatriation General Hospital
🇦🇺Concord, New South Wales, Australia
Nepean Hospital
🇦🇺Kingswood, New South Wales, Australia
Instituto Goiano de Gastroenterologia e Endoscopia Digestiva Ltda
🇧🇷Goiania, Goias, Brazil
MHAT "Hadzhi Dimitar", OOD
🇧🇬Sliven, Bulgaria
London Health Science Centre
🇨🇦London, Ontario, Canada
Clinical Hospital Centre Rijeka
🇭🇷Rijeka, Croatia
Toronto Digestive Disease Associates, Inc.
🇨🇦Vaughan, Ontario, Canada
Clinical Hospital Dubrava
🇭🇷Zagreb, Croatia
Hepato-Gastroenterologie HK, s.r.o.
🇨🇿Hradec Kralove, Czechia
West Tallinn Central Hospital
🇪🇪Tallinn, Estonia
Medizinische Hochschule Hannover
🇩🇪Hannover, Niedersachsen, Germany
Obudai Egeszsegugyi Centrum Kft.
🇭🇺Budapest, Hungary
EUGASTRO GmbH
🇩🇪Leipzig, Sachsen, Germany
Tolna Megyei Balassa Janos Korhaz
🇭🇺Szekszard, Hungary
Szent Janos Korhaz es Eszak-budai Egyesitett Korhazak
🇭🇺Budapest, Hungary
IRCCS Ospedale Casa Sollievo della Sofferenza
🇮🇹San Giovanni Rotondo, Foggia, Italy
I.R.C.C.S Policlinico San Donato
🇮🇹San Donato Milanese, Milano, Italy
Yeungnam University Hospital
🇰🇷Daegu, Korea, Republic of
Hospital of Lithuanian University of Health Sciences Kaunas Clinics
🇱🇹Kaunas, Lithuania
Vilnius University Hospital Santariskiu Clinic, Public Institution
🇱🇹Vilnius, Lithuania
Universidad Autonoma de Nuevo Leon, Hospital Universitario Dr. Jose Eleuterio Gonzalez
🇲🇽Monterrey, Nuevo Leon, Mexico
Albert Schweitzer Ziekenhuis, Dordwijk
🇳🇱Dordrecht, Netherlands
SP CSK im. prof. K. Gibinskiego SUM
🇵🇱Katowice, Poland
Centralny Szpital Kliniczny MSW w Warszawie
🇵🇱Warszawa, Poland
Institutul Clinic Fundeni
🇷🇴Bucuresti, Romania
TSBIH "Territorial Clinical Hospital"
🇷🇺Krasnoyarsk, Russian Federation
SBIH of Yaroslavl region " Regional Clinical Hospital "
🇷🇺Yaroslavl, Russian Federation
Clinical Center Kragujevac
🇷🇸Kragujevac, Serbia
Clinical Center Zvezdara
🇷🇸Belgrade, Serbia
Gastro I, s.r.o.
🇸🇰Presov, Slovakia
RCI Chernivtsi RCH Dep of Surgery Bukovinian SMU
🇺🇦Chernivtsi, Ukraine
Marmara University Pendik Research and Training Hospital
🇹🇷Istanbul, Turkey
Kyiv CCH #12 Dept of Therapy O.O.Bogomolets NMU
🇺🇦Kyiv, Ukraine
Whipps Cross University Hospital
🇬🇧London, Greater London, United Kingdom
Pest Megyei Flor Ferenc Korhaz
🇭🇺Kistarcsa, Hungary
Gabinet Endoskopii Przewodu Pokarmowego
🇵🇱Krakow, Poland
Santa Familia Centrum Badan, Profilaktyki i Leczenia
🇵🇱Lodz, Poland
Centrum Onkologii-Instytut im. M. Sklodowskiej Curie
🇵🇱Warszawa, Poland
Spitalul Clinic Colentina
🇷🇴Bucuresti, Romania
S.C Centrul de Gastroenterologie Dr. Goldis S.R.L
🇷🇴Timisoara, Romania
Clinical Center Bezanijska kosa
🇷🇸Belgrade, Serbia
UMHAT 'Tsaritsa Yoanna - ISUL', EAD
🇧🇬Sofia, Bulgaria
"City Clinic UMHAC" EOOD
🇧🇬Sofia, Bulgaria
UMHAT "Sv. Ivan Rilski", EAD
🇧🇬Sofia, Bulgaria
Clinical Hospital Centre Osijek
🇭🇷Osijek, Croatia
SPZOZ Uniwersytecki Szpital Klin. nr 1 im.N.Barlickiego UM
🇵🇱Lodz, Poland
Twoja Przychodnia-Szczecinskie Centrum Medyczne
🇵🇱Szczecin, Poland
Nzoz Vivamed
🇵🇱Warszawa, Poland
Ars-Medica S.C Rybak Maria, Rybak Zbigniew
🇵🇱Wroclaw, Poland
Clinical Center of Vojvodina
🇷🇸Novi Sad, Serbia
SP ZOZ Wojewodzki Szpital Zespolony im. J. Sniadeckiego
🇵🇱Bialystok, Poland
GI L.T.Malaya Therapy National Institute of the NAMS of Ukraine
🇺🇦Kharkiv, Ukraine
MCIC MC LLC Health Clinic
🇺🇦Vinnytsia, Ukraine
Gastro One
🇺🇸Germantown, Tennessee, United States
Atlanta Gastroenterology Specialists, PC
🇺🇸Suwanee, Georgia, United States
The Alfred Hospital
🇦🇺Melbourne, Victoria, Australia
Tri-State Gastroenterology Associates
🇺🇸Crestview Hills, Kentucky, United States
Tyler Research Institute, LLC
🇺🇸Tyler, Texas, United States