Clinical trial NCT03259334: Efficacy and Safety Study of SHP647 as Induction Therapy in Participants With Moderate to Severe Ulcerative Colitis
Official title: A Phase 3 Randomized, Double-blind, Placebo-controlled, Parallel-group Efficacy and Safety Study of SHP647 as Induction Therapy in Subjects With Moderate to Severe Ulcerative Colitis (FIGARO UC 301)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Ulcerative Colitis
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2017-08-23
Enrollment: 380
Sex: ALL
Minimum age (years): 16
Maximum age (years): 80
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the efficacy of SHP647 in inducing remission, based on composite score of participant-reported symptoms and centrally read endoscopy, in participants with moderate to severe ulcerative colitis (UC).


Eligibility criteria: Inclusion Criteria:

* Participants and/or their parent or legally authorized representative must have an understanding, ability, and willingness to fully comply with study procedures and restrictions.
* Participants must be able to voluntarily provide written, signed, and dated informed consent and/or assent, as applicable, to participate in the study.
* Participants must be between greater than or equal to (\>=)16 and \<=80 years of age at the time of the signing of the informed consent/assent form.
* Participants less than (\<) 18 years of age must weigh \>=40 kg and must have body mass index (BMI) \>=16.5 kilogram per square meter (kg/m\^2).
* Participants must have a documented diagnosis of UC for \>=3 months before screening. The following must be available in each participant's source documentation:

  1. A biopsy report to confirm the histological diagnosis.
  2. A report documenting disease duration based upon prior colonoscopy. Note: If this documentation is not available at the time of screening, a colonoscopy with biopsy to confirm the diagnosis is required during the screening period.
* Participants must be willing to undergo a flexible sigmoidoscopy or colonoscopy, including biopsy sample collection, during screening after all other inclusion criteria have been met.
* Participants must have moderate to severe active UC, defined as a total Mayo score of \>=6, including a centrally read endoscopic subscore \>=2, rectal bleeding subscore \>=1, and stool frequency subscore \>=1 at baseline.
* Participants must have evidence of UC extending proximal to the rectum (ie, not limited to proctitis).
* Participants must have had an inadequate response to, or lost response to, or had an intolerance to at least 1 conventional treatment such as mesalamine (5-aminosalicylate \[ASA\]), glucocorticoids, immunosuppressants (azathioprine \[AZA\], 6-mercaptopurine \[6-MP\], or methotrexate \[MTX\]), or anti-tumor necrosis factor (TNF).
* Participants receiving any treatment(s) for UC are eligible provided they have been, and are anticipated to be, on a stable dose for the designated period of time.
* Participants are males or nonpregnant, nonlactating females who, if sexually active, agree to comply with the contraceptive requirements of the protocol, or females of nonchildbearing potential.

Exclusion Criteria:

- Participants with indeterminate colitis, microscopic colitis, non-steroidal anti-inflammatory drug-induced colitis, ischemic colitis, infectious colitis, or clinical/histologic findings suggestive of Crohn's disease.

* Participants with colonic dysplasia or neoplasia. (Participants with prior history of adenomatous polyps will be eligible if the polyps have been completely removed.)
* Participants with past medical history or presence of toxic megacolon.
* Participants with colonic stricture, past medical history of colonic resection, a history of bowel surgery within 6 months before screening, or who are likely to require surgery for UC during the treatment period.
* Participants at risk for colorectal cancer must have a colonoscopy performed during the screening period with results available within 10 days before the baseline visit, unless the participant has had a surveillance colonoscopy performed within 1 year prior to screening, and any adenomatous polyps found at that examination have been excised. Colonoscopy report and pathology report (if biopsies are obtained) from the colonoscopy performed during screening or in the prior year confirming no evidence of dysplasia and colon cancer must be available in the source documents.

Participants at risk for colorectal cancer include, but are not limited to:

1. Participants with extensive colitis for \>=8 years or disease limited to left side of colon (ie, distal to splenic flexure) for \>=10 years before screening, regardless of age.
2. Participants \>=50 years of age at the time of signing of the informed consent form.

   - Participants have had prior treatment with SHP647.

   - Participants with known or suspected intolerance or hypersensitivity to the investigational product(s), closely related compounds, or any of the stated ingredients.

   - Participants have received anti-TNF treatment within 60 days before baseline.

   - Participants have received any biologic with immunomodulatory properties (other than anti-TNFs) within 90 days before baseline.

   - Participants have received any nonbiologic treatment with immunomodulatory properties (other than their current background UC treatment) within 30 days before baseline.

   - Participants have ever received anti-integrin/adhesion molecule treatment (example (eg): natalizumab, vedolizumab, efalizumab, etrolizumab, or any other investigational anti-integrin/adhesion molecule).

   - Participants have received parenteral or rectal glucocorticoids, or rectal 5-ASA, within 14 days before screening endoscopic procedure.

   - Participants have received leukocyte apheresis or selective lymphocyte, monocyte, or granulocyte apheresis or plasma exchange within 30 days before baseline.

   - Participants have participated in other investigational studies within either 30 days or 5 half-lives of investigational product used in the study (whichever is longer) before baseline.

   - Participants have received a live (attenuated) vaccine within 30 days before the baseline visit.

   - Participants with active enteric infections (positive stool culture and sensitivity), Clostridium difficile infection or pseudomembranous colitis \[Participants with C. difficile infection at screening may be allowed re-test after treatment\], evidence of active cytomegalovirus infection or Listeria monocytogenes, known active invasive fungal infections such as histoplasmosis or parasitic infections, clinically significant underlying disease that could predispose the participants to infections, or a history of serious infection (requiring parenteral antibiotic and/or hospitalization) within 4 weeks before the baseline visit.

   - Participants with abnormal chest x-ray findings at screening, such as presence of active tuberculosis, general infections, heart failure, or malignancy.

   - Participants with evidence of active or latent infection with Mycobacterium tuberculosis (TB) or participants with this history who have not completed a generally accepted full course of treatment before randomization are excluded. All other participants must have either the Mantoux (purified protein derivative \[PPD\]) tuberculin skin test or interferon gamma release assay (IGRA) performed.

Participants who have no history of previously diagnosed active or latent tuberculosis are excluded if they have a positive Mantoux (PPD) tuberculin skin test (ie \>=5 millimeter \[mm\] induration) or a positive IGRA (the latter to be tested at the site's local laboratory) during screening or within 12 weeks before screening. If IGRA test cannot be performed locally, a central laboratory may be used, with prior agreement from the sponsor.

1. An IGRA is strongly recommended for participants with a prior Bacillus Calmette-Guerin (BCG) vaccination, but may be used for any participant. Documentation of IGRA product used and the test result must be in the participant's source documentation if performed locally. Acceptable IGRA products include QuantiFERON TB Gold Plus In-Tube Test.
2. If the results of the IGRA are indeterminate, the test may be repeated, and if a negative result is obtained, enrollment may proceed. In participants with no history of treated active or latent tuberculosis, a positive test on repeat will exclude the participant. Participants with a history of active or latent TB infection must follow instructions for "participants with a prior diagnosis of active or latent TB are excluded unless both of the following criteria are met" in this criterion.
3. Participants with repeat indeterminate IGRA results, with no prior TB history, may be enrolled after consultation with a pulmonary or infectious disease specialist who determines low risk of infection (ie, participant would be acceptable for immunosuppressant \[eg, anti-TNF\] treatment without additional action). This consultation must be included in source documentation.

Results from a chest x-ray, taken within the 12 weeks before or during screening must show no abnormalities suggestive of active TB infection as determined by a qualified medical specialist.

Participants with a prior diagnosis of active or latent TB are excluded unless both of the following criteria are met:

1. The participant has previously received an adequate course of treatment for either latent (eg, 9 months of isoniazid or an acceptable alternative regimen, in a locale where rates of primary multidrug TB resistance are \<5%. Participants from regions with higher rates of primary multidrug TB resistance are excluded) or active (acceptable multidrug regimen) TB infection. Evidence of diagnosis and treatment must be included in source documentation. Consultation with a pulmonary or infectious disease specialist to confirm adequate treatment (ie, participant would be acceptable for immunosuppressant \[eg, anti-TNF\] treatment without additional action) must be performed during the screening period. The consultation report must be included in source documentation prior to enrollment.
2. A chest x-ray performed within 12 weeks before or during screening indicates no evidence of active or recurrent disease, and documentation of interpretation by a qualified medical specialist must be included in source documentation.

   * Participants with a pre-existing demyelinating disorder such as multiple sclerosis or new onset seizures, unexplained sensory motor, or cognitive behavioral, neurological deficits, or significant abnormalities noted during screening.
   * Participants with any unexplained symptoms suggestive of progressive multifocal leukoencephalopathy (PML) based on the targeted neurological assessment during the screening period.
   * Participants with a transplanted organ. Skin grafts to treat pyoderma gangrenosum are allowed.
   * Participants with a significant concurrent medical condition at the time of screening or baseline, including, but not limited to, the following:

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1. Any major illness/condition or evidence of an unstable clinical condition (eg, renal, hepatic, hematologic, gastrointestinal (except disease under study), endocrine, cardiovascular, pulmonary, immunologic \[eg, Felty's syndrome\], or local active infection/infectious illness) that, in the investigator's judgment will substantially increase the risk to the participant if he or she participates in the study.
2. Cancer or history of cancer or lymphoproliferative disease within the previous 5 years (other than resected cutaneous basal cell carcinoma, squamous cell carcinoma, or carcinoma in situ of the uterine cervix that has been treated with no evidence of recurrence).
3. Presence of acute coronary syndrome (eg, acute myocardial infarction, unstable angina pectoris) within 24 weeks before screening.
4. History of significant cerebrovascular disease within 24 weeks before screening.

   * Participants who have had significant trauma or major surgery within 4 weeks before the screening visit, or with any major elective surgery scheduled to occur during the study.
   * Participants with evidence of cirrhosis with or without decompensation.
   * Participants with primary sclerosing cholangitis.
   * Participants with evidence of positive hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb).

Note: If a participant tests negative for HBsAg, but positive for hepatitis B virus (HBcAb), the participant would be considered eligible if no presence of HBV DNA is confirmed by HBV DNA polymerasechainreaction(PCR) reflex testing performed in the central laboratory.

- Participants with chronic hepatitis C (HCV) (positive HCVAb and HCVRNA). Note: Participants who are HCVAb positive without evidence of HCVRNA may be considered eligible (spontaneous viral clearance or previously treated and cured \[defined as no evidence of HCV RNA at least 12 weeks prior to baseline\]).

- Participants with any of the following abnormalities in hematology and/or serum chemistry profiles during screening.

Note: Screening laboratory tests, if the results are considered by the investigator to be transient and inconsistent with the participant's clinical condition, may be repeated once during the screening period for confirmation. Results must be reviewed for eligibility prior to the screening endoscopy procedure.

1. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels \>=3.0×upper limit of normal (ULN).
2. Total bilirubin level \>=1.5×ULN or \>2.0×ULN if the participant has a known documented history of Gilbert's syndrome.
3. Hemoglobin level \<=80 gram per liter (g/L) (8.0 gram per deciliter \[g/dL\]).
4. Platelet count \<=100×10\^9 per liter (/L) (100,000 cells per cubic millimeter \[mm\^3\]) or \>=1000×10\^9/L (1,000,000 cells/mm\^3).
5. White blood cell count \<=3.5×10\^9/L (3500 cells/mm\^3). - Absolute neutrophil count (ANC)\<2×10\^9/L (2000 cells/mm\^3).

   * Serum creatinine level \>1.5 × ULN or estimated glomerular filtration rate \<30 ml/min/1.73m\^2 based on the abbreviated Modification of Diet in Renal Disease Study Equation.

Note: If platelet count is \<150,000 cells/mm\^3, a further evaluation should be performed to rule out cirrhosis, unless another etiology has already been identified.

- Participants with known human immunodeficiency virus (HIV) infection based on documented history, with positive serological test, or positive HIV serologic test at screening, tested at the site's local laboratory in accordance with country requirements or tested at the central laboratory.

Note: A documented negative HIV test within 6 months of screening is acceptable and does not need to be repeated.

- Participants who have, or who have a history of (within 2 years before screening), serious psychiatric disease, alcohol dependency, or substance/drug abuse or dependency of any kind, including abuse of medical marijuana (cannabis).

- Participants with any other severe acute or chronic medical or psychiatric condition or laboratory or electrocardiogram (ECG) abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the participant inappropriate for entry into this study.

* Female participants who are planning to become pregnant during study period.
* Participants who do not agree to postpone donation of any organ or tissue, including male participants who are planning to bank or donate sperm and female participants who are planning to harvest or donate eggs, for the duration of the study and through 16 weeks after last dose of investigational product.
* Participants who are investigational site staff members or relatives of those site staff members or Participants who are Shire employees directly involved in the conduct of study.

Primary outcomes:
measure: Number of Participants With Remission at Week 12
timeFrame: At Week 12
Secondary outcomes:
measure: Number of Participants With Endoscopic Remission at Week 12
timeFrame: At Week 12
measure: Number of Participants With Clinical Remission at Week 12
timeFrame: At Week 12
measure: Number of Participants With Clinical Response Based on Composite Score at Week 12
timeFrame: At Week 12
measure: Number of Participants With Mucosal Healing Based on Endoscopic and Histological Assessment Using the Geboes Score Grading System at Week 12
timeFrame: At Week 12
measure: Number of Participants With Remission Based on Total Mayo Score at Week 12
timeFrame: At Week 12
measure: Number of Participants With Clinical Response Based on Total Mayo Score at Week 12
timeFrame: At Week 12
measure: Number of Participants With Partial Mayo Score <=2 With no Individual Sub-score Greater Than (>) 1 at Weeks 4, 8, and 12
timeFrame: At Weeks 4, 8, and 12
measure: Number of Participants With Clinical Remission With Stool Frequency Sub-scores of 0 or 1 and Rectal Bleeding Sub-score of 0 at Weeks 4 and 8
timeFrame: At Weeks 4 and 8
measure: Number of Participants With Endoscopic Remission With Sub-score of 0 at Week 12
timeFrame: At Week 12
measure: Number of Participants With Clinical Remission With Both Rectal Bleeding and Stool Frequency Sub-scores of 0 at Weeks 4, 8, and 12
timeFrame: At Weeks 4, 8, and 12
measure: Number of Participants With Deep Remission at Week 12
timeFrame: At Week 12
measure: Change From Baseline in Average Worst Abdominal Pain Score Based on Patient Reported Outcome-ulcerative Colitis (PRO-UC) Daily e-Diary at Week 12
timeFrame: Baseline, Week 12
measure: Change From Baseline in Diarrhea (Average Loose Bowel Movements) Score Based on PRO-UC Daily e-Diary at Week 12
timeFrame: Baseline, Week 12
measure: Change From Baseline in Average Bowel Movements With Urgency Score Based on PRO-UC Daily e-Diary at Week 12
timeFrame: Baseline, Week 12
measure: Change From Baseline in Absolute Stool Frequency (Average Number of Bowel Movements) Score Based on PRO-UC Daily e-Diary at Week 12
timeFrame: Baseline, Week 12
measure: Change From Baseline in Absolute Rectal Bleeding (Average Number Bowel Movements With Blood) Score Based on PRO-UC Daily e-Diary at Week 12
timeFrame: Baseline, Week 12
measure: Change From Baseline in Total Sign/Symptom Score Based on PRO-UC Daily e-Diary at Week 12
timeFrame: Baseline, Week 12
measure: Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Domains Scores at Weeks 8 and 12
timeFrame: Baseline, Weeks 8 and 12
measure: Change From Baseline in IBDQ Total Scores at Weeks 8 and 12
timeFrame: Baseline, Weeks 8 and 12
measure: Change From Baseline in Short Form-36 Health Survey (SF-36), Version 2, Acute (Physical and Mental Component Summary Scores) at Week 12
timeFrame: Baseline, Week 12
measure: Change From Baseline in Short Form-36 Health Survey (SF-36), Version 2, Acute (Individual Domain Scores) at Week 12
timeFrame: Baseline, Week 12
measure: Number of Participants Based on In-patient Hospitalization
timeFrame: Baseline up to Week 12
measure: Median Duration of Total In-patient Days
timeFrame: Baseline up to Week 12
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: Atria Clinical Research - Clinedge - PPDS
state: Arkansas
city: Lancaster
country: United States
facility: OM Research LLC - Lancaster - ClinEdge - PPDS
state: California
city: Rialto
country: United States
facility: Inland Empire Liver Foundation
state: California
city: Colorado Springs
country: United States
facility: Peak Gastroenterology Associates
state: Colorado
city: Colorado Springs
country: United States
facility: Asthma and Allergy Associates PC - CRN - PPDS
state: Colorado
city: Coral Gables
country: United States
facility: Advanced Clinical Research Network
state: Florida
city: Miami
country: United States
facility: Nuren Medical and Research Center
state: Florida
city: Naples
country: United States
facility: Gastroenterology Group of Naples
state: Florida
city: Orlando
country: United States
facility: Omega Research Consultants LLC - Clinedge - PPDS
state: Florida
city: Saint Augustine
country: United States
facility: East Coast Institute for Research, LLC
state: Florida
city: Columbus
country: United States
facility: Gastrointestinal Diseases, Inc. Research
state: Georgia
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Chicago
country: United States
facility: University of Chicago Medical Center
state: Illinois
city: Evansville
country: United States
facility: Medisphere Medical Research Center LLC
state: Indiana
city: Michigan City
country: United States
facility: Laporte County Institute For Clinical Research
state: Indiana
city: Lake Charles
country: United States
facility: Clinical Trials of SWLA LLC
state: Louisiana
city: Shreveport
country: United States
facility: Louisiana Research Center LLC
state: Louisiana
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Ocean Springs
country: United States
facility: Digestive Health Center PA
state: Mississippi
city: Brooklyn
country: United States
facility: New York Total Medical Care PC
state: New York
city: Statesville
country: United States
facility: Piedmont Healthcare
state: North Carolina
city: Cincinnati
country: United States
facility: Consultants For Clinical Research Inc
state: Ohio
city: Cincinnati
country: United States
facility: Consultants For Clinical Research Inc
state: Ohio
city: Fairfield
country: United States
facility: Consultants For Clinical Research Inc
state: Ohio
city: Pittsburgh
country: United States
facility: Allegheny Center For Digestive Health
state: Pennsylvania
city: Wyomissing
country: United States
facility: Digestive Disease Associates
state: Pennsylvania
city: Germantown
country: United States
facility: Gastro One
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Union City
country: United States
facility: Advanced Gastroenterology-Union City
state: Tennessee
city: Baytown
country: United States
facility: Inquest Clinical Research/Coastal Gastroenterology Associates, PA
state: Texas
city: Cypress
country: United States
facility: Northside Gastroenterology
state: Texas
city: Tomball
country: United States
facility: DM Clinical Research - ERN - PPDS
state: Texas
city: Bountiful
country: United States
facility: HP Clinical Research
state: Utah
city: Seattle
country: United States
facility: Digestive Health Center at UWMC
state: Washington
city: Seattle
country: United States
facility: University of Washington
state: Washington
city: Tacoma
country: United States
facility: CHI Franciscan Digestive Care Associates
state: Washington
city: Elkins
country: United States
facility: Exemplar Research, Inc. - Elkins
state: West Virginia
city: Morgantown
country: United States
facility: West Virginia University Hospital
state: West Virginia
city: Concord
country: Australia
facility: Concord Repatriation General Hospital
state: New South Wales
city: Liverpool
country: Australia
facility: Liverpool Hospital
state: New South Wales
city: Herston
country: Australia
facility: Royal Brisbane & Women's Hospital
state: Queensland
city: South Brisbane
country: Australia
facility: Mater Hospital Brisbane
state: Queensland
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Fitzroy
country: Australia
facility: St Vincents Hospital Melbourne - PPDS
state: Victoria
city: Melbourne
country: Australia
facility: The Alfred Hospital
state: Victoria
city: St. Veit an der Glan
country: Austria
facility: A.ö. Krankenhaus der Barmherzigen Brüder
state: Kärnten
city: Graz
country: Austria
facility: LKH-Universitätsklinikum Klinikum Graz
state: Steiermark
city: Klagenfurt am Wörthersee
country: Austria
facility: Klinikum Klagenfurt Am Woerthersee
city: Salzburg
country: Austria
facility: Salzburger Landeskliniken
city: St. Pölten
country: Austria
facility: Universitätsklinikum St. Pölten
city: Wels
country: Austria
facility: Klinikum Wels-Grieskirchen GmbH
city: Wien
country: Austria
facility: Medizinische Universitat Wien (Medical University of Vienna)
city: Goiânia
country: Brazil
facility: Instituto Goiano de Gastroenterologia E Endoscopia Digestiva Ltda
state: Goiás
city: Passo Fundo
country: Brazil
facility: Hospital Da Cidade de Passo Fundo
state: Rio Grande Do Sul
city: Santo André
country: Brazil
facility: CEMEC - Centro Multidisciplinar de Estudos Clínicos
state: São Paulo
city: Zagreb
country: Croatia
facility: University Hospital Center Zagreb
state: Grad Zagreb
city: Karlovac
country: Croatia
facility: Opca Bolnica Karlovac
state: Karlovacka Županija
city: Bjelovar
country: Croatia
facility: Opca bolnica Bjelovar
city: Osijek
country: Croatia
facility: Clinical Hospital Centre Osijek
city: Split
country: Croatia
facility: University Hospital Centre Split
city: Virovitica
country: Croatia
facility: General Hospital Virovitica
city: Vukovar
country: Croatia
facility: General County Hospital Vukovar and Croatian Veterans Hospital
city: Zadar
country: Croatia
facility: General Hospital Zadar
city: Hradec Kralove
country: Czechia
facility: Hepato-Gastroenterologie HK, s. r. o.
state: Královéhradecký Kraj
city: Olomouc
country: Czechia
facility: PreventaMed s.r.o.
state: Olomoucký Kraj
city: Praha 4
country: Czechia
facility: Institut Klinicke A Experimentalni Mediciny
city: Praha 7
country: Czechia
facility: ISCARE I.V.F. a.s.
city: Usti nad Labem
country: Czechia
facility: Krajska zdravotni, a.s. - Masarykova nemocnice v Usti nad Labem, o.z.
city: Usti nad Orlici
country: Czechia
facility: Nemocnice Pardubickeho kraje, a.s. Orlickoustecka nemocnice
city: Ulm
country: Germany
facility: Universitätsklinikum Ulm
state: Baden-Württemberg
city: Aachen
country: Germany
facility: Universitätsklinikum der RWTH Aachen
state: Nordrhein-Westfalen
city: Münster
country: Germany
facility: Gastro Campus Research GbR
state: Nordrhein-Westfalen
city: Kiel
country: Germany
facility: Universitatsklinikum Schleswig-Holstein
state: Schleswig-Holstein
city: Jena
country: Germany
facility: Universitätsklinikum Jena
state: Thüringen
city: Berlin-Zehlendorf
country: Germany
facility: Gastroenterologische Facharztpraxis am Mexikoplatz
city: Berlin
country: Germany
facility: Charité - Universitätsmedizin Berlin
city: Biberach an der Riss
country: Germany
facility: Sana Klinikum Biberach
city: Frankfurt
country: Germany
facility: Universitätsklinikum Frankfurt
city: Hamburg
country: Germany
facility: Asklepios Westklinikum Hamburg Ggmbh
city: Köln
country: Germany
facility: Uniklinik Köln
city: Munich
country: Germany
facility: Klinikum rechts der Isa der Technischen Universitaet Muenchen
city: Jerusalem
country: Israel
facility: Shaare Zedek Medical Center
city: Jerusalem
country: Israel
facility: Hadassah Medical Center - PPDS
city: Nahariya
country: Israel
facility: Galilee Medical Center
city: Nazareth
country: Israel
facility: Nazareth EMMS Hospital
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center PPDS
city: Tiberias
country: Israel
facility: Baruch Padeh Poriya Medical Center
city: Catanzaro
country: Italy
facility: Azienda Ospedaliera Mater Domini Di Catanzaro
state: Calabria
city: Modena
country: Italy
facility: Azienda Ospedaliero Universitaria Di Modena Policlinico
state: Emilia-Romagna
city: Roma
country: Italy
facility: Azienda Ospedaliera San Camillo Forlanini
state: Lazio
city: San Giovanni Rotondo (FG)
country: Italy
facility: Ospedale Casa Sollievo Della Sofferenza IRCCS
state: Puglia
city: Firenze
country: Italy
facility: Azienda Ospedaliera Universitaria Careggi
state: Toscana
city: Negrar
country: Italy
facility: Ospedale Sacro Cuore Don Calabria
state: Veneto
city: Padova
country: Italy
facility: Azienda Ospedale Università Padova - Dipartimento Salute della Donna e del Bambino - INCIPIT - PIN
state: Veneto
city: Bologna
country: Italy
facility: Azienda Ospedaliero Universitaria Di Bologna - Policlinico S Orsola Malpighi
city: Novara
country: Italy
facility: A.O.U. Maggiore della Carità
city: Pavia
country: Italy
facility: Fondazione IRCCS Policlinico San Matteo di Pavia
city: Roma
country: Italy
facility: La Sapienza-Università di Roma-Policlinico Umberto I
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario A Gemelli
city: Rozzano (MI)
country: Italy
facility: Istituto Clinico Humanitas
city: Torino
country: Italy
facility: Azienda Ospedaliera Città della Salute e della Scienza di Torino
city: Torino
country: Italy
facility: Azienda Ospedaliera Ordine Mauriziano di Torino
city: Sapporo-shi
country: Japan
facility: Sapporo Tokushukai Hospital
state: Hokkaidô
city: Sagamihara
country: Japan
facility: Sagamihara Kyodo Hospital
state: Kanagawa
city: Minato-ku
country: Japan
facility: Jikei University Hospital
state: Tokyo
city: Minato-ku
country: Japan
facility: Kitasato University Kitasato Institute Hospital
state: Tokyo
city: Ome
country: Japan
facility: Ome Municipal General Hospital
state: Tokyo
city: Abiko-shi, Chiba
country: Japan
facility: Tokatsu Tsujinaka Hospital
city: Hakodate
country: Japan
facility: Hakodate Koseiin Hakodate Goryoukaku Hospital
city: Koganei
country: Japan
facility: Kawabe Clinic
city: Koga
country: Japan
facility: Yuai Memorial Hospital
city: Koshigaya
country: Japan
facility: Dokkyo Medical University Saitama Medical Center
city: Kurume-shi
country: Japan
facility: Hidaka Coloproctology Clinic
city: Nagakute
country: Japan
facility: Aichi Medical University Hospital
city: Nishinomiya
country: Japan
facility: Nishinomiya Municipal Central Hospital
city: Onomichi
country: Japan
facility: Onomichi General Hospital
city: Otsu-Shi
country: Japan
facility: Shiga University of Medical Science Hospital
city: Sapporo
country: Japan
facility: Sapporo Higashi Tokushukai Hospital
city: Beppu
country: Japan
facility: Shinbeppu Hospital
state: Ôita
city: Kaunas
country: Lithuania
facility: Hospital of Lithuanian University of Health Sciences Kaunas Clinics
city: Vilnius
country: Lithuania
facility: Vilnius University Hospital Santaros Klinikos
city: Vilnius
country: Lithuania
facility: Vilnius City Clinical Hospital
city: Tilburg
country: Netherlands
facility: ETZ-Elisabeth
state: Noord-Brabant
city: Alkmaar
country: Netherlands
facility: NWZ, location Alkmaar
state: Noord-Holland
city: Leiden
country: Netherlands
facility: Leids Universitair Medisch Centrum
state: Zuid-Holland
city: Amsterdam
country: Netherlands
facility: VU Medisch Centrum
city: Amsterdam
country: Netherlands
facility: Academisch Medisch Centrum Amsterdam
city: Wroclaw
country: Poland
facility: Melita Medical
state: Dolnoslaskie
city: Wroclaw
country: Poland
facility: Lexmedica
state: Dolnoslaskie
city: Bydgoszcz
country: Poland
facility: Vitamed Galaj i Cichomski sp.j.
state: Kujawsko-pomorskie
city: Torun
country: Poland
facility: Gastromed Kopon Zmudzinski i Wspolnicy Sp.j.Specjalistyczne Centrum Gastrologii i Endoskopii Specj
state: Kujawsko-pomorskie
city: Wloclawek
country: Poland
facility: Centrum Diagnostyczno - Lecznicze Barska sp. z o.o.
state: Kujawsko-pomorskie
city: Lódz
country: Poland
facility: Niepubliczny Zaklad Opieki Zdrowotnej CENTRUM MEDYCZNE Szpital Swietej Rodziny
state: Lódzkie
city: Lódz
country: Poland
facility: SPZOZ Uniwersytecki Szpital Kliniczny im. Wojskowej Akademii Medycznej UM w Lodzi
state: Lódzkie
city: Lódz
country: Poland
facility: Instytut Centrum Zdrowia Matki Polki
state: Lódzkie
city: Krakow
country: Poland
facility: Krakowskie Centrum Medyczne
state: Malopolskie
city: Warszawa
country: Poland
facility: Centrum Medyczne Warszawa - PRATIA - PPDS
state: Mazowieckie
city: Warszawa
country: Poland
facility: Niepubliczny Zakład Opieki Zdrowotnej VIVAMED
state: Mazowieckie
city: Warszawa
country: Poland
facility: Miedzyleski Szpital Specjalistyczny w Warszawie
state: Mazowieckie
city: Bialystok
country: Poland
facility: Uniwersytecki Szpital Kliniczny w Bialymstoku
state: Podlaskie
city: Sopot
country: Poland
facility: Endoskopia Sp. z o.o.
state: Pomorskie
city: Tychy
country: Poland
facility: H-T. Centrum Medyczne Endoterapia
state: Slaskie
city: Konskie
country: Poland
facility: Szpital Specjalistyczny sw Lukasza - Oddzial Gastroenterologii
state: Swietokrzyskie
city: Szczecin
country: Poland
facility: Twoja Przychodnia - Szczecińskie Centrum Medyczne
state: Zachodniopomorskie
city: Bydgoszcz
country: Poland
facility: Szpital Uniwersytecki Nr 2 im. Dr Jana Biziela w Bydgoszczy
city: Bydgoszcz
country: Poland
facility: Centrum Medyczne Pratia Bydgoszcz
city: Czestochowa
country: Poland
facility: Centrum Medyczne Czestochowa - PRATIA - PPDS
city: Gdynia
country: Poland
facility: Centrum Medyczne Gdynia - PRATIA - PPDS
city: Józefów
country: Poland
facility: BioVirtus Centrum Medyczne
city: Katowice
country: Poland
facility: Szpital Zakonu Bonifratrow pw. Aniolow Strozow w Katowicach
city: Katowice
country: Poland
facility: NZOZ All Medicus
city: Krakow
country: Poland
facility: Centrum Medyczne A-Z Clinic Mateusz Sidor, Piotr Puc-Lekarze Spolka Partnerska
city: Ksawerow
country: Poland
facility: Centrum Opieki Zdrowotnej Orkan-Med Stec-Michalska Sp. J.
city: Lodz
country: Poland
facility: Med Gastr Sp.z.o.o Sp.k
city: Nowa Sól
country: Poland
facility: Twoja Przychodnia - Centrum Medyczne Nowa Sol
city: Piaseczno
country: Poland
facility: Centrum Innowacyjnych Terapii
city: Poznan
country: Poland
facility: Clinical Research Center Spółka z Ograniczoną Odpowiedzialnością, Medic-R Spółka Komandytowa
city: Rzeszow
country: Poland
facility: Korczowski Bartosz, Gabinet Lekarski
city: Szczecin
country: Poland
facility: Sonomed Sp. z o.o.
city: Warsaw
country: Poland
facility: Centrum Zdrowia MDM
city: Warszawa
country: Poland
facility: Centralny Szpital Kliniczny MSW
city: Zamosc
country: Poland
facility: Samodzielny Publiczny Szpital Wojewodzki im. Papieza Jana Pawla II
city: Cluj-Napoca
country: Romania
facility: Cluj-Napoca Emergency Clinical County Hospital
state: Cluj
city: Bucharest
country: Romania
facility: Dr.Carol Davila Emergency University Central Military Hospital
city: Bucharest
country: Romania
facility: Sana Monitoring SRL
city: Bucharest
country: Romania
facility: Colentina Clinical Hospital
city: Bucharest
country: Romania
facility: Prof. Dr. Matei Bals Institute of Infectious Diseases
city: Bucharest
country: Romania
facility: Fundeni Clinical Institute
city: Bucuresti
country: Romania
facility: Centrul Medical Hifu Terramed Conformal S.R.L.
city: Constanta
country: Romania
facility: Affidea Romania SRL
city: Iasi
country: Romania
facility: Gastromedica SRL
city: Oradea
country: Romania
facility: Dr. Tirnaveanu Amelita Private Practice
city: Timisoara
country: Romania
facility: Dr. Goldis Gastroenterology Center SRL
city: Kazan
country: Russian Federation
facility: Kazan State Medical University
city: Moscow
country: Russian Federation
facility: Moscow Clinical Scientific Center
city: Moscow
country: Russian Federation
facility: Moscow Regional Research Clinical Institute Na Mfvladimirskiy
city: Nizhny Novgorod
country: Russian Federation
facility: Nizhegorodskaya Regional Clinical Hospital n.a. Semashko
city: Novosibirsk
country: Russian Federation
facility: Research Institute of Physiology and Basic Medicine
city: Rostov-on-Don
country: Russian Federation
facility: Rostov State Medical University
city: Rostov-on-Don
country: Russian Federation
facility: Rostov State Medical University
city: Saint Petersburg
country: Russian Federation
facility: Russian Medical Military Academy n.a. S.M. Kirov
city: Saint-Petersburg
country: Russian Federation
facility: Union Clinic, LLC
city: Samara
country: Russian Federation
facility: Medical University Reaviz
city: Samara
country: Russian Federation
facility: Private Healthcare Institution Clinical Hospital RZD-Medicina of Samara city
city: Samara
country: Russian Federation
facility: Medical Company Hepatolog, LLC
city: Saratov
country: Russian Federation
facility: SHI Regional Clinical Hospital
city: Smoensk
country: Russian Federation
facility: Smolensk Regional Clinical Hospital
city: St. Petersburg
country: Russian Federation
facility: St. Elizabeth Municipal Clinical Hospital
city: St. Petersburg
country: Russian Federation
facility: First St. Petersburg State Medical University n.a. I.P Pavlov
city: Stavropol
country: Russian Federation
facility: Stavropol State Medical University
city: Tyumen
country: Russian Federation
facility: Regional Consulting and Diagnostics Centre
city: Belgrade
country: Serbia
facility: Clinical Hospital Center ''Bezanijska Kosa''
city: Nis
country: Serbia
facility: University Clinical Center Nis
city: Vrsac
country: Serbia
facility: General Hospital Vrsac
city: Kragujevac
country: Serbia
facility: University Clinical Center Kragujevac
state: Šumadijski Okrug
city: Johannesburg
country: South Africa
facility: CLINRESCO, ARWYP Medical Suites
state: Gauteng
city: Pretoria
country: South Africa
facility: Dr. J Breedt
state: Gauteng
city: Claremont
country: South Africa
facility: Dr JP Wright
state: Western Cape
city: Lancashire
country: United Kingdom
facility: Fairfield General Hospital - PPDS
state: Bury
city: Lancashire
country: United Kingdom
facility: Pennine Acute Hospitals Trust
state: Bury
city: London
country: United Kingdom
facility: Whipps Cross University Hospital
state: London, City Of
city: North Shields
country: United Kingdom
facility: North Tyneside General Hospital
state: Northumberland
city: Shrewsbury
country: United Kingdom
facility: Royal Shrewsbury Hospital
state: Shropshire
city: Aberdeen
country: United Kingdom
facility: Aberdeen Royal Infirmary - PPDS
city: Edinburh
country: United Kingdom
facility: Western General Hospital Edinburgh - PPDS
city: Newport
country: United Kingdom
facility: Royal Gwent Hospital - PPDS
city: Wolverhampton
country: United Kingdom
facility: New Cross Hospital
Study officials:
affiliation: Shire
name: Study Director
role: STUDY_DIRECTOR
References: