Phase 2 Dose-finding IMU-838 for Ulcerative Colitis
- Conditions
- Ulcerative Colitis
- Interventions
- Drug: IMU-838Drug: Placebo
- Registration Number
- NCT03341962
- Lead Sponsor
- Immunic AG
- Brief Summary
This is a phase 2, multicenter, randomized, double-blind, placebo-controlled, dose-finding study to evaluate the efficacy and safety of IMU-838 for induction and maintenance therapy with an option for open-label treatment extension in moderate-to-severe ulcerative colitis (CALDOSE-1).
- Detailed Description
The investigational medicinal product (IMP) IMU-838 (vidofludimus calcium) is a new compound that selectively inhibits the human enzyme dihydroorotate dehydrogenase (DHODH). Dihydroorotate dehydrogenase plays a major role in the de-novo pyrimidine synthesis and is specifically expressed at high levels in proliferating or activated lymphocytes. Resting lymphocytes satisfy their pyrimidine requirements through a DHODH-independent salvage pathway. Thus, IMU-838-mediated DHODH inhibition selectively affects activated, rapidly proliferating lymphocytes. The metabolic stress secondary to DHODH inhibition leads to a reduction of pro-inflammatory cytokine release including interleukin (IL)-17 (IL-17A and IL-17F) and interferon gamma (IFNγ), and to an increased apoptosis in activated lymphocytes.
This is a phase 2, multicenter, randomized, double-blind, and placebo-controlled trial in patients with moderate-to-severe UC with an option for open-label treatment extension. The study comprises a blinded induction phase to establish the optimal dose of IMU-838 to induce response and remission, a blinded maintenance phase to evaluate the potential of IMU-838 to maintain remission until Week 50, and an open-label treatment extension arm for all patients who discontinue the blinded phase as scheduled or prematurely, subject to certain restrictions. A subset of patients will undergo a pharmacokinetic (PK) period at the start of the open-label period to establish a full single-dose PK profile.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 263
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description 10 mg IMU-838 (Maintenance) IMU-838 Two 5 mg tablets once daily of IMU-838 until Week 50 or ulcerative colitis relapse. placebo (Induction) Placebo The placebo tablets will be identical to the IMU-838 tablets in terms of appearance, constitution of inactive ingredients, and packaging. 10 mg IMU-838 (Induction) IMU-838 Two 5 mg tablets once daily of IMU-838 for 10 to 22 weeks depending on symptomatic remission at Weeks 10 or 22. Patients will receive only half of their assigned full dose during the first week of treatment. 30 mg IMU-838 (Induction) IMU-838 Two 15 mg tablets once daily of IMU-838 for 10 to 22 weeks depending on symptomatic remission at Weeks 10 or 22. Patients will receive only half of their assigned full dose during the first week of treatment. 45 mg IMU-838 (Induction) IMU-838 Two 22.5 mg tablets once daily of IMU-838 for 10 to 22 weeks depending on symptomatic remission at Weeks 10 or 22. Patients will receive only half of their assigned full dose during the first week of treatment. 30 mg IMU-838 (Maintenance) IMU-838 Two 15 mg tablets once daily of IMU-838 until Week 50 or ulcerative colitis relapse. placebo (Maintenance) Placebo The placebo tablets will be identical to the IMU-838 tablets in terms of appearance, constitution of inactive ingredients, and packaging. Patients who have received placebo during the induction phase will be 're-randomized' to continue to receive placebo (in a blinded fashion). 30 mg IMU-838 (Open-label) IMU-838 Two 15 mg tablets once daily of IMU-838 or one 30 mg tablet IMU-838 once daily for up to 10 years and up to 3 years in UK sites
- Primary Outcome Measures
Name Time Method Induction Phase: Symptomatic Remission and Endoscopic Healing at Week 10 10 weeks Composite endpoint: Proportion of patients with both, symptomatic remission (Mayo rectal bleeding subscore = 0, and Mayo stool frequency subscore of 0 or 1) and endoscopic healing (Modified Mayo endoscopy subscore of 0 or 1) at Week 10.
All patients who were randomized to 30 mg/day and 45 mg/day were used for the assessment of the primary efficacy endpoint
- Secondary Outcome Measures
Name Time Method Induction Phase: Symptomatic Remission and Endoscopic Healing at Different Doses at Week 10 10 weeks Proportion of patients with both symptomatic remission and endoscopic healing at Week 10 (all individual IMU-838 doses were compared with one another and to placebo)
Induction Phase: Symptomatic Remission 22 weeks Proportion of patients achieving symptomatic remission (Mayo rectal bleeding subscore = 0, and Mayo stool frequency subscore of 0 or 1) during the induction phase
Safety: Adverse Events 50 weeks Incidence and Severity of AEs during the induction and maintenance phases
Induction Phase: Time to Achieving Symptomatic Remission 22 weeks Time to achieving symptomatic remission (Mayo rectal bleeding subscore = 0 and Mayo stool frequency subscore of 0 or 1) within the extended induction phase
Induction Phase: Proportion of Patients With Clinical Response 10 weeks Proportion of patients with clinical response (decrease from Baseline in the full Mayo score of at least 3 points and at least 30%, with an accompanying decrease in the subscore for rectal bleeding of at least 1 point or an absolute subscore for rectal bleeding of 0 or 1) at Week 10
Induction Phase: Proportion of Patients With Endoscopic Healing 10 weeks Proportion of patients with endoscopic healing (Modified Mayo endoscopy subscore of 0 or 1) at Week 10
Induction Phase: Proportion of Patients With Symptomatic Response 22 weeks Proportion of patients with symptomatic response (≥1-point decrease from Baseline in Mayo PRO-2 score) during the induction phase (including extended induction phase)
Induction Phase: Full Mayo Score 10 weeks Change in full Mayo Score from Baseline to Week 10. The full Mayo score is composed of 4 categories (bleeding, stool frequency, physician assessment, and endoscopic appearance) each rated from 0 to 3 that are added up to give a total score that ranges from 0 to 12. A higher score indicates a worse outcome.
Induction Phase: Partial Mayo Score 22 weeks Change in partial mayo score over 10 or 22 weeks. The partial Mayo score includes only the non-invasive Mayo subscores, ie, stool frequency, rectal bleeding, and physician's global assessment (each rated from 0 to 3 that are added up to give a total score that ranges from 0 to 9). A higher score indicates a worse outcome.
Induction Phase: Patient Reported Outcome (PRO)-2 Mayo Score 22 weeks Change in PRO-2 Mayo score over 10 or 22 weeks. Mayo PRO-2 score, ie, stool frequency and rectal bleeding score each rated from 0 to 3 that are added up to give a total score that ranges from 0 to 6. A higher score indicates a worse outcome.
Induction Phase: Fecal Calprotectin (fCP) 22 weeks Time course of biomarker fCP in stool samples during extended induction phase
Induction Phase: C-reactive Protein (CRP) 22 weeks Time course of biomarker CRP in blood samples during extended induction phase
Safety: Number of Participants With Clinically Significant Findings During Physical Examination 50 weeks The emergence of any clinically significant findings compared to screening captured during the induction and maintenance phases
Safety: Body Weight 50 weeks Changes in body weight during the induction and maintenance phases
Safety: Blood Pressure 50 weeks Changes in blood pressure (mm Hg) during the induction and maintenance phases
Safety: Heart Rate 50 weeks Changes in heart rate (beats per minute) during the induction and maintenance phases
Safety: 12-lead Electrocardiogram (ECG) 50 weeks Number of patients with clinically significant changes in ECG
Safety: Hematology up to Week 50 Number of participants with abnormal hematology laboratory values (treatment-emergent adverse events \[TEAEs\] related to hematological abnormalities)
Safety: Blood Chemistry 50 weeks Number of participants with abnormal blood chemistry laboratory values (TEAES related to clinical chemistry abnormalities)
Safety: Coagulation 10 weeks Number of participants with clinically significant abnormal coagulation laboratory values
Safety: Urinalysis 50 weeks Number of participants with abnormal urinalysis laboratory values (TEAEs related to urinalysis)
Safety: Micro Ribonucleic Acid-122 Expression 24 hours Micro ribonucleic acid-122 (miR-122) expression (before first dose and 24 hours after first dose - foldchange of normalized expression values )
PK: IMU-838 Plasma Level 2 weeks Measurement of post-dose blood plasma levels of IMU-838 at Week 2
PK: Time to Cmax (Tmax) pre-dose, 1, 2, 3, 4, 5, 6 hours post PK dose; 24 hours post PK dose; 48 hours post PK dose; 72 hours post PK dose Single-dose PK measurement of Tmax in a subset of patients in the open-label phase
Pharmacodynamics (PK): IMU-838 Trough Level Day 0, Day 1, Day 7, Week 2 and Week 10 Measurement of pre-dose (trough) blood plasma levels of IMU-838 throughout the induction period
PK: Area Under the Drug Concentration-time Curve (AUC) From Time Zero to 24 Hours (AUC0-24h) pre-dose, 1, 2, 3, 4, 5, 6 hours post PK dose; 24 hours post PK dose; 48 hours post PK dose; 72 hours post PK dose Single-dose PK measurement of AUC0-24h in a subset of patients in the open-label phase
PK: AUC Time Zero to Infinity (AUC0-inf) pre-dose, 1, 2, 3, 4, 5, 6 hours post PK dose; 24 hours post PK dose; 48 hours post PK dose; 72 hours post PK dose Single-dose PK measurement of AUC0-inf in a subset of patients in the open-label phase
PK: AUC Time Zero to Last Measurable Concentration (AUC0-t) pre-dose, 1, 2, 3, 4, 5, 6 hours post PK dose; 24 hours post PK dose; 48 hours post PK dose; 72 hours post PK dose Single-dose PK measurement of AUC0-t in a subset of patients in the open-label phase
PK: Maximum Plasma Concentration (Cmax) pre-dose, 1, 2, 3, 4, 5, 6 hours post PK dose; 24 hours post PK dose; 48 hours post PK dose; 72 hours post PK dose Single-dose PK measurement of Cmax in a subset of patients in the open-label phase
Maintenance Phase: Proportion of Patients in Symptomatic Remission Week 14, Week 30, Week 50 Proportion of patients in symptomatic remission (Mayo rectal bleeding subscore = 0, and Mayo stool frequency subscore of 0 or 1) by visit up to Week 50 in maintenance phase
Maintenance Phase: Time to Relapse 50 weeks Time to symptomatic ulcerative colitis (UC) relapse
Maintenance Phase: Proportion of Patients Without Relapse 50 weeks Proportion of patients without symptomatic UC relapse until Week 50
Maintenance Phase: fCP 50 weeks Timecourse of biomarker fCP in stool samples
Maintenance Phase: CRP 50 weeks Timecourse of biomarker CRP in blood samples
Maintenance Phase: Proportion of Patients With Endoscopic Healing 50 weeks Proportion of patients with endoscopic healing (Modified Mayo endoscopy subscore of 0 or 1) at Week 50 of maintenance phase
Maintenance Phase: Proportion of Patients With Microscopic Healing 50 weeks Proportion of patients with microscopic healing (Geboes score of =\< 3.1) at Week 50 of maintenance phase
Maintenance Phase: Corticosteroid-free Remission 50 weeks Corticosteroid-free clinical remission (clinical remission and no receipt of systemic or local corticosteroids) at Week 50 in patients receiving corticosteroids at Baseline
Open-label Phase: Symptom Control up to 4 years Proportion of patients with symptom control
Open-label Phase: fCP Baseline, Week 4 OLE, Week 8 OLE, EoT up to 4 years (variable) Timecourse of biomarker fCP in stool samples. Visits were scheduled every 4 weeks (+/-7 days) until 50 weeks of total study participation (ie induction + extended induction, if applicable, maintenance + open-label part) and every 10 weeks (+/-7 days) thereafter. The visit schedule in the OLE after 50 weeks of overall study treatment was changed from a 10-week schedule to a 24 week (+/-14 days) schedule after Protocol Version 6.0 came into force.
Because the study was terminated early, EoT varied between patients depending on when patients entered the study and the time a patient participated in the induction and maintenance phases before switching to the OLE.Open-label Phase: CRP Baseline, Week 4 OLE, Week 8 OLE, Week 10 OLE, Week 12 OLE, Week 16 OLE, Week 20 OLE, Week 24 OLE, Week 28 OLE, Week 32 or 38 OLE (depending if entry was after extended induction phase), EoT up to 4 years (variable) Timecourse of biomarker CRP in blood samples. Visits were scheduled every 4 weeks (+/-7 days) until 50 weeks of total study participation (ie induction + extended induction, if applicable, maintenance + open-label part) and every 10 weeks (+/-7 days) thereafter. The visit schedule in the OLE after 50 weeks of overall study treatment was changed from a 10-week schedule to a 24 week (+/-14 days) schedule after Protocol Version 6.0 came into force.
Because the study was terminated early, EoT varied between patients depending on when patients entered the study and the time a patient participated in the induction and maintenance phases before switching to the OLE.Maintenance Phase: Mayo PRO-2 Score 50 weeks Time course of Mayo PRO-2 score until Week 50. Mayo patient-reported outcome score, ie, stool frequency and rectal bleeding score each rated from 0 to 3 3 that are added up to give a total score that ranges from 0 to 6. A higher score indicates a worse outcome.
Trial Locations
- Locations (130)
University Clinic for Hematology - Skopje - Macedonian Hematology Association
🇲🇰Skopje, North Macedonia
Alliance Medical Research, LLC
🇺🇸Lighthouse Point, Florida, United States
Del Sol Research Management, LLC
🇺🇸Tucson, Arizona, United States
Ventura Clinical Trials
🇺🇸Ventura, California, United States
Gomel Regional Clinical Hospital
🇧🇾Gomel, Belarus
Medley Research Associates
🇺🇸Medley, Florida, United States
University Hospital Center Mother Teresa
🇦🇱Tirana, Albania
SOLUMED Centrum Medyczne
🇵🇱Poznań, Poland
Multiprofile Hospital for Active Treatment "Dr. Hristo Stambolski" EOOD
🇧🇬Kazanlak, Bulgaria
Medical Center Exacta Medica
🇧🇬Pleven, Bulgaria
Artroscan s.r.o.
🇨🇿Ostrava - Třebovice, Czechia
Polyclinic Solmed Zagreb
🇭🇷Zagreb, Croatia
Klinika Medifem
🇵🇱Warszawa, Poland
S.C. MEDLIFE S.A., Sectia Gastroenterologie
🇷🇴Bucharest, Romania
Hospital da Senhora da Oliveira - Guimarães, EPE
🇵🇹Guimarães, Portugal
Central Clinical Hospital of the Russian Academy of Sciences
🇷🇺Moscow, Russian Federation
Clinical Hospital Center Zemun
🇷🇸Belgrade, Serbia
Centrum Medyczne Med-Gastr Sp. z o.o. Spółka Komandytowa
🇵🇱Łódz, Poland
FSBEI HE "Military Medical Academy n.a. S.M. Kirov" under the Ministry of Defence of Russian Federation
🇷🇺Saint Petersburg, Russian Federation
Kyiv Regional Clinical Hospital No 2
🇺🇦Kyiv, Ukraine
Municipal Non-profit Enterprise "Vinnytsia Regional Clinical Hospital named after M.I. Pyrogova of Vinnytsia Regional Council, Regional Specialized Clinical Gastroenterological Center,
🇺🇦Vinnytsia, Ukraine
Municipal Non-profit Enterprise of Lviv Regional Council "Lviv Regional Clinical Hospital", proctology department, Danylo Galytsky Lviv National Medical University, Chair of Surgery #1
🇺🇦Lviv, Ukraine
Research Center Eco-Safety, LLC
🇷🇺Saint Petersburg, Russian Federation
City Hospital No. 5 - Sochi
🇷🇺Sochi, Russian Federation
Global Life Research LLC
🇺🇸Miami, Florida, United States
Atlanta Gastroenterology Associates, LLC
🇺🇸Atlanta, Georgia, United States
McFarland Clinic, P.C.
🇺🇸Ames, Iowa, United States
First Street Surgical Hospital
🇺🇸Bellaire, Texas, United States
PMG Research of Salisbury, LLC
🇺🇸Salisbury, North Carolina, United States
Clinical Trials of South Carolina
🇺🇸Charleston, South Carolina, United States
Digestive Health Specialists
🇺🇸Tacoma, Washington, United States
Durres Regional Hospital
🇦🇱Durres, Albania
Republican Scientific and Practical Center for Radiation Medicine and Human Ecology
🇧🇾Gomel, Belarus
University Clinical Hospital Mostar, Internal Medicine Clinic, Department of Gastroenterology
🇧🇦Mostar, Bosnia and Herzegovina
Multiprofile Hospital for Active Treatment Blagoevgrad AD
🇧🇬Blagoevgrad, Bulgaria
Mhat Byala
🇧🇬Byala, Bulgaria
Medical Center "Medconsult Pleven" OOD
🇧🇬Pleven, Bulgaria
Medical Center "Hera" EOOD
🇧🇬Sofia, Bulgaria
General Hospital Bjelovar
🇭🇷Bjelovar, Croatia
University Multiprofile Hospital for Active Treatment "Sveti Georgi" EAD, Plovdiv, Gastroenterology clinic
🇧🇬Plovdiv, Bulgaria
Diagnostic-Consulting Center "Convex" EOOD
🇧🇬Sofia, Bulgaria
Clinical Hospital Center Osijek
🇭🇷Osijek, Croatia
Clinical Hospital Center Split
🇭🇷Zagreb, Croatia
General Hospital Vukovar
🇭🇷Vukovar, Croatia
Clinical Hospital Center Zagreb
🇭🇷Zagreb, Croatia
Clinical Hospital Center Rijeka
🇭🇷Rijeka, Croatia
Clinical Hospital Dubrava
🇭🇷Zagreb, Croatia
Hepato-Gastroenterologie HK, s.r.o. Poliklinika III
🇨🇿Hradec Králové, Czechia
Asclepiades - Interna a gastroenterologie s.r.o. - Havířov
🇨🇿Havířov, Czechia
MEDICON a.s. - Poliklinika Budějovická Gastroenterologie
🇨🇿Praha, Czechia
FaraCol s.r.o. - Prague
🇨🇿Praha, Czechia
Klinika ResTrial
🇨🇿Praha, Czechia
Všeobecná fakultní nemocnice v Praze IV. interní klinika VFN a 1. LF UK
🇨🇿Praha, Czechia
Academician Z.Tskhakaia West Georgia National Center of Interventional Medicine
🇬🇪Kutaisi, Georgia
LTD Unimedi Kakheti - Caraps Medline
🇬🇪Tbilisi, Georgia
Amsterdam UMC, locatie AMC
🇳🇱Amsterdam, Netherlands
Albert Schweitzer Hospital
🇳🇱Dordrecht, Netherlands
Elisabeth-TweeSteden Hospital
🇳🇱Tilburg, Netherlands
City General Hospita 8th September
🇲🇰Skopje, North Macedonia
Centrum Usług Medycznych MaxMed
🇵🇱Bochnia, Poland
Centrum Medyczne Pratia Gdynia
🇵🇱Gdynia, Poland
Vita Longa Sp. z o.o.
🇵🇱Katowice, Poland
GLOBE Badania Kliniczne Sp. z o.o.
🇵🇱Kłodzko, Poland
Samodzielny Publiczny Szpital Kliniczny Nr 4 w Lublinie Oddział Gastroenterologii
🇵🇱Lublin, Poland
Ars Medical - Szpital, Ars Medical - Ambulatorium
🇵🇱Piła, Poland
Niepubliczny Zakład Opieki Zdrowotnej Centrum Medyczne HCP - Lecznictwo Stacjonarne
🇵🇱Poznań, Poland
Endoskopia Sp. z o.o.
🇵🇱Sopot, Poland
Centrum Badawcze Współczesnej Terapii, Prywatny Gabinet Lekarski dr Anna Bochenek-Mularczyk
🇵🇱Warszawa, Poland
Centrum Medyczne OMNI Clinic Sp. z o.o. Spółka Komandytowa
🇵🇱Wrocław, Poland
Przychodnia Vistamed
🇵🇱Wroclaw, Poland
Centro Hospitalar e Universitário de Coimbra, EPE - Hospitais da Universidade de Coimbra
🇵🇹Coimbra, Portugal
Spitalul Clinic Colentina, Sectia Gastroenterologie
🇷🇴Bucharest, Romania
Institutul Clinic Fundeni, Sectia Clinica Gastroenterologie III
🇷🇴Bucharest, Romania
S.C. Cabinet Particular Policlinic Algomed SRL, Specialitatea Gastroenterologie
🇷🇴Timisoara, Romania
SEI HPE "Kuban State Medical University" of MoH and SD, CBHS Regional Clinical Hospital No.2
🇷🇺Krasnodar, Russian Federation
Kazan State Medical University
🇷🇺Kazan, Russian Federation
Federal Medical Biophysical Center n.a. Burnazyan
🇷🇺Moscow, Russian Federation
Novosibirskiy Gastrocenter, LLC
🇷🇺Novosibirsk, Russian Federation
Clinical Research Institution of Moscow Region named after M. F. Vladimirsky
🇷🇺Moscow, Russian Federation
Hospital of Saint Martyr Elizaveta
🇷🇺Saint Petersburg, Russian Federation
Gastroenterological Center "Expert" LLC
🇷🇺Saint Petersburg, Russian Federation
Saint Petersburg State Medical University named after I.P. Pavlov
🇷🇺Saint Petersburg, Russian Federation
Istanbul Universitesi Istanbul Tip Fakultesi Gastroenteroloji Bilim Dali
🇹🇷Fatih, Turkey
Regional State Autonomous Healthcare Institution "Tomsk Regional Clinical Hospital"
🇷🇺Tomsk, Russian Federation
Siberian State Medical University
🇷🇺Tomsk, Russian Federation
Clinic for gastroenterohepatology
🇷🇸Belgrade, Serbia
General Hospital Leskovac
🇷🇸Leskovac, Serbia
Clinical Center Nis
🇷🇸Nis, Serbia
Clinical Center Kragujevac
🇷🇸Kragujevac, Serbia
Bezmiâlem Vakıf Üniversitesi
🇹🇷Fatih, Turkey
Hospital Juan Ramón Jimenez
🇪🇸Huelva, Spain
Karadeniz Teknik Üniversitesi Tip Fakultesi
🇹🇷Trabzon, Turkey
Public Enterprise "Dnipropetrovsk regional clinical hospital named after I.I. Mechnikova", Department of Gastroenterology (Hepatology)
🇺🇦Dnipro, Ukraine
MNPE "Regional Clinical Hospital of Ivano-Frankivsk Regional Council", Gastroenterology Department, SHEI "Ivano-Frankivsk National Medical University", Chair of Internal Medicine #1
🇺🇦Ivano-Frankivs'k, Ukraine
Ivano-Frankivsk City Clinical Hospital No. 1
🇺🇦Ivano-Frankivs'k, Ukraine
Municipal Non-profit Enterprise "City Clinical Hospital #2 named after prof. O.O. Shalimova", of Kharkiv City Council, Proctology Department
🇺🇦Kharkiv, Ukraine
Private Enterprise Private Manufacturing Firm "Acinus", Treatment and diagnostic Centre
🇺🇦Kropyvnytskyi, Ukraine
Municipal Non-profit Enterprise of Kharkiv Regional Council "Regional Clinical Hospital", Gastroenterology Department
🇺🇦Kharkiv, Ukraine
Medical Center Medical Clinic Blagomed LLC
🇺🇦Kyiv, Ukraine
Shalimov's National Institute of surgery and transplantation
🇺🇦Kyiv, Ukraine
Kyiv City Clinical Hospital #1, Therapeutics Department #2
🇺🇦Kyiv, Ukraine
Medical Centre of Limited Liability Company "Medical Centre "Consilium Medical", clinico-consultation department
🇺🇦Kyiv, Ukraine
Medical Centre of Limited Liability Company "Medical Centre "Dopomoga plus""
🇺🇦Kyiv, Ukraine
Volyn Regional Clinical Hospital
🇺🇦Lutsk, Ukraine
KARDIOKOM Ltd.
🇺🇦Mykolaiv, Ukraine
Municipal Non-profit Enterprise "Vinnytsia City Clinical Hospital #1, Gastroenterology Department, Vinnytsia National Medical University named after M.I.Pyrogova, Chair of Propaedeutics of Internal Medicine
🇺🇦Vinnytsia, Ukraine
Transcarpathian Regional Clinical Hospital named after Andriy Novaka, gastroenterology department
🇺🇦Uzhhorod, Ukraine
Barts Health NHS Trust, of Royal London Hospital
🇬🇧London, United Kingdom
London North West University Healthcare NHS Trust (LNWH), St Mark's Hospital, R&D Department, Northwick Park Hospital
🇬🇧Harrow, United Kingdom
University College London Hospitals NHS Foundation Trust
🇬🇧London, United Kingdom
St Helens & Knowsley Teaching Hospitals NHS Trust, Whiston Hospital
🇬🇧Prescot, United Kingdom
University Hospitals Coventry and Warwickshire NHS Trust, University Hospital
🇬🇧Shrewsbury, United Kingdom
Shrewsbury and Telford Hospitals NHS Trust, Royal Shrewsbury Hospital
🇬🇧Shrewsbury, United Kingdom
The Royal Wolverhampton NHS Trust, New Cross Hospital
🇬🇧Wolverhampton, United Kingdom
Centro Hospitalar de Entre o Douro e Vouga, EPE - Hospital São Sebastião
🇵🇹Santa Maria da Feira, Portugal
Regional Hospital of Shkoder
🇦🇱Shkoder, Albania
Vitiebsk State Order of Peoples' Friendship Medical University
🇧🇾Vitebsk, Belarus
University Clinical Centre of the Republic of Srpska, Internal Medicine Clinic, Department of Gastroenterology and Hepatology
🇧🇦Banja Luka, Bosnia and Herzegovina
University Hospital Center Bezaniska Kosa
🇷🇸Belgrade, Serbia
General Hospital Djordje Joanovic, Internal Deases Department, Gastroenterology
🇷🇸Zrenjanin, Serbia
Centrum Medyczne Endo-med Sp. z o.o.
🇵🇱Karczew, Poland
Zakład leczniczy ALLMEDICA BADANIA KLINICZNE Sp. z o.o. Sp. K.
🇵🇱Nowy Targ, Poland
Salve Medica Sp. z o.o. Spółka Komandytowa
🇵🇱Łódź, Poland
Etyka Ośrodek Badań Klinicznych
🇵🇱Olsztyn, Poland
Kyiv City Clinical Hospital #18, Proctology Department, National Medical University named after O.O.Bogomolets, Chair of Surgery #1
🇺🇦Kyiv, Ukraine
Municipal Institution "Zaporizhzhska Regional Clinical Hospital" of Zaporizhzha Regional Council, gastroenterology department
🇺🇦Zaporizhzhya, Ukraine
Family Clinical Trials
🇺🇸Pembroke Pines, Florida, United States
Clinical Research Trials of Florida, Inc.
🇺🇸Tampa, Florida, United States
Axis Clinical Trials
🇺🇸Los Angeles, California, United States
Commonwealth Clinical Studies
🇺🇸Brockton, Massachusetts, United States