Efficacy and Safety Study of SHP647 as Induction Therapy in Participants With Moderate to Severe Ulcerative Colitis

Ulcerative Colitis Clinical Trial

— FIGARO UC 301  

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)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03259334
• Other study ID #: SHP647-301
• Secondary ID: 2017-000599-27
• Status: Terminated
• Phase: Phase 3
• Start date: February 9, 2018
• Est. completion date: October 23, 2020

Study information

• Verified date: June 2021
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 380
• Est. completion date: October 23, 2020
• Est. primary completion date: July 22, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years to 80 Years

Eligibility

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:

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.

Related Conditions & MeSH terms

• Colitis
• Colitis, Ulcerative
• Ulcer
• Ulcerative Colitis

Intervention

Drug:
• Ontamalimab
Participants will receive 1 mL of SHP647 sterile aqueous buffered solution at an appropriate concentration to provide the intended dose of drug (25 or 75 mg).

Other:
• Placebo
Participants will receive 1 mL of sterile aqueous buffered solution.

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Shire

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Brazil,  Croatia,  Czechia,  Germany,  Israel,  Italy,  Japan,  Lithuania,  Netherlands,  Poland,  Romania,  Russian Federation,  Serbia,  South Africa,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Remission at Week 12	Remission was defined as a composite score of patient-reported symptoms using daily e-diary and centrally read endoscopy as stool frequency sub-score of 0 or 1 with at least a 1-point change from baseline, rectal bleeding sub-score of 0 and endoscopic sub-score of 0 or 1 (modified, excluded friability). The composite score was a recommended measure consisted of the Mayo score without the physician global assessment (PGA) sub-score and ranged from 0 to 9 points. The Mayo score was a measure of Ulcerative Colitis (UC) disease activity. It ranged from 0 to 12 points and consisted of 4 sub-scores, each graded from 0 to 3 with higher scores indicating more severe disease. The sub-scores were stool frequency (0-3); rectal bleeding (0-3); findings of endoscopy (0-3); PGA (0-3).	At Week 12
Secondary	Number of Participants With Endoscopic Remission at Week 12	Endoscopic remission was defined by centrally read endoscopic sub-score 0 or 1 (modified, excluded friability). The centrally read endoscopic sub-score of Mayo score ranged from 0 to 3 with higher scores indicating more severe disease.	At Week 12
Secondary	Number of Participants With Clinical Remission at Week 12	Clinical remission was defined by stool frequency (SF) sub-score of 0 or 1 with at least a 1-point change from baseline in stool frequency sub-score, and rectal bleeding sub-score of 0. Rectal bleeding is assessed on a scale from 0-3, where 0: no blood seen, 1: streaks of blood with stool less than half time, 2: obvious blood or streaks of blood with stool most of the time, and 3: blood alone passes. Stool frequency is assessed on a scale from 0-3, where 0: normal number of stools for this participant, 1: 1 to 2 stools more than normal, 2: 3 to 4 stools more than normal, and 3: 5 or more stools more than normal. Higher scores indicated more severe disease.	At Week 12
Secondary	Number of Participants With Clinical Response Based on Composite Score at Week 12	Clinical response based on composite score was defined as a decrease from baseline in the composite score of patient-reported symptoms using daily e-diary and centrally read endoscopy of at least 2 points and at least 30 percent (%), with an accompanying decrease in the sub-score for rectal bleeding greater than or equal to (>=) 1 point or a sub-score for rectal bleeding less than or equal to (<=) 1. The composite score was a recommended measure derived from the Mayo score without the PGA sub-score and ranged from 0 to 9 points. The Mayo score was a measure of UC disease activity. It ranged from 0 to 12 points and consisted of 4 sub-scores, each graded from 0 to 3 with higher scores indicating more severe disease The sub-scores were stool frequency (0-3); rectal bleeding (0-3); findings of endoscopy (0-3); PGA (0-3).	At Week 12
Secondary	Number of Participants With Mucosal Healing Based on Endoscopic and Histological Assessment Using the Geboes Score Grading System at Week 12	Mucosal healing was defined by centrally read endoscopic sub-score 0 or 1 (modified, excluded friability) and centrally read Geboes score of <=2. The centrally read endoscopic sub-score of Mayo score ranged from 0 to 3 with higher scores indicating more severe disease. Geboes score grading system was a validated score for evaluating histologic disease activity in UC as follows: Grade 0 equal to (=) structural and architectural changes; Grade 1 = chronic inflammatory infiltrate; Grade 2 = lamina propria neutrophils and eosinophils; Grade 3 = neutrophils in the epithelium; Grade 4 = crypt destruction; Grade 5 = erosions or ulceration. A higher Geboes score indicating more severe disease.	At Week 12
Secondary	Number of Participants With Remission Based on Total Mayo Score at Week 12	Remission was defined as a total Mayo score of <=2 with no individual sub-score (stool frequency, rectal bleeding, endoscopy [modified, excluded friability], and PGA) exceeding 1. The Total Mayo score ranged from 0 to 12 points and consisted of 4 sub-scores, each graded from 0 to 3 with higher scores indicating more severe disease: stool frequency (0-3); rectal bleeding (0-3); findings of endoscopy (0-3); PGA (0-3).	At Week 12
Secondary	Number of Participants With Clinical Response Based on Total Mayo Score at Week 12	Clinical response (Mayo) was defined as a decrease from baseline in the total Mayo score of at least 3 points and at least 30%, with an accompanying decrease in the sub-score for rectal bleeding >=1 point or an absolute sub-score for rectal bleeding <=1. The Total Mayo score ranged from 0 to 12 points and consisted of the following 4 sub-scores, each graded from 0 to 3 with higher scores indicating more severe disease: stool frequency (0-3); rectal bleeding (0-3); findings of endoscopy (0-3); PGA (0-3).	At Week 12
Secondary	Number of Participants With Partial Mayo Score <=2 With no Individual Sub-score Greater Than (>) 1 at Weeks 4, 8, and 12	The partial Mayo score ranged from 0 to 9 points and consisted of the following 3 sub-scores, each graded from 0 to 3 with higher scores indicating more severe disease: Stool frequency (0-3); Rectal bleeding (0-3); PGA (0-3). The partial Mayo score did not include the endoscopy sub-score.	At Weeks 4, 8, and 12
Secondary	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	Clinical remission was defined as stool frequency sub-score of 0 or 1 with at least a 1-point change from baseline in stool frequency sub-score, and a rectal bleeding sub-score of 0. Rectal bleeding was assessed on a scale from 0-3, where 0: no blood seen, 1: streaks of blood with stool less than half time, 2: obvious blood or streaks of blood with stool most of the time, and 3: blood alone passes. Stool frequency was assessed on a scale from 0-3, where 0: normal number of stools for this participant, 1: 1 to 2 stools more than normal, 2: 3 to 4 stools more than normal, and 3: 5 or more stools more than normal. Higher scores indicated more severe disease	At Weeks 4 and 8
Secondary	Number of Participants With Endoscopic Remission With Sub-score of 0 at Week 12	Endoscopic remission was defined by centrally read endoscopic sub-score 0 (modified, excluded friability). The centrally read endoscopic sub-score of Mayo score ranged from 0 to 3 with higher scores indicating more severe disease.	At Week 12
Secondary	Number of Participants With Clinical Remission With Both Rectal Bleeding and Stool Frequency Sub-scores of 0 at Weeks 4, 8, and 12	Clinical remission was defined as both rectal bleeding and stool frequency sub-scores of 0. Rectal bleeding was assessed on a scale from 0-3, where 0: no blood seen, 1: streaks of blood with stool less than half time, 2: obvious blood or streaks of blood with stool most of the time, and 3: blood alone passes. Stool frequency was assessed on a scale from 0-3, where 0: normal number of stools for this participant, 1: 1 to 2 stools more than normal, 2: 3 to 4 stools more than normal, and 3: 5 or more stools more than normal. Higher scores indicated more severe disease.	At Weeks 4, 8, and 12
Secondary	Number of Participants With Deep Remission at Week 12	Deep remission was defined as both endoscopic and rectal bleeding sub-scores of 0, and stool frequency sub-score <=1 and a centrally read Geboes score of <=2. The stool frequency sub-score, rectal bleeding sub-score and endoscopic sub-score of Mayo score ranged from 0 to 3 with higher scores indicating more severe disease. The composite score was a recommended measure consisted of the Mayo score without the PGA sub-score and ranged from 0 to 9 points. Geboes score grading system was a validated score for evaluating histologic disease activity in UC as follows: Grade 0 = structural and architectural changes; Grade 1 = chronic inflammatory infiltrate; Grade 2 = lamina propria neutrophils and eosinophils; Grade 3 = neutrophils in the epithelium; Grade 4 = crypt destruction; Grade 5 = erosions or ulceration. A higher Geboes score indicating more severe disease.	At Week 12
Secondary	Change From Baseline in Average Worst Abdominal Pain Score Based on Patient Reported Outcome-ulcerative Colitis (PRO-UC) Daily e-Diary at Week 12	PRO-UC daily e-diary data was collected using a daily e-diary during the treatment period. Collection of the daily e-diary data was begun at least 10 days before the baseline visit. Participants were asked to record the signs and symptom data of abdominal pain worst severity, as experienced over the previous 24 hours, in the e-diary. Participant's signs and symptom average scores at each scheduled visit were calculated based on data recorded over the most recent 3 days (consecutive or non-consecutive) of the last 10 days prior to scheduled visit start date excluding the following days: day of any bowel preparation, day of endoscopy, any days between day of bowel preparation and day of endoscopy, and the 2 days after the day of endoscopy. Abdominal pain's worst severity assessment was based on an 11-point numerical rating scale with 0 anchor at "No pain" and 10 at "Worst Imaginable Pain" as experienced over the previous 24 hours, in e-diary. Higher scores indicating more severe pain.	Baseline, Week 12
Secondary	Change From Baseline in Diarrhea (Average Loose Bowel Movements) Score Based on PRO-UC Daily e-Diary at Week 12	PRO-UC daily e-diary data was collected using a daily e-diary during the treatment period. Collection of the daily e-diary data was begun at least 10 days before the baseline visit. Participants were asked to record the signs and symptom data for number of loose bowel movement, as experienced over the previous 24 hours, in the e-diary. Participant's signs and symptom average scores at each scheduled visit were calculated based on data recorded over the most recent 3 days (consecutive or nonconsecutive) of the last 10 days prior to the scheduled visit start date excluding the following days: day of any bowel preparation, day of endoscopy, any days between day of bowel preparation and day of endoscopy, and the 2 days after the day of endoscopy. Average number of loose bowel movement ranged from 0-27. Higher scores indicating more frequent bowel movements.	Baseline, Week 12
Secondary	Change From Baseline in Average Bowel Movements With Urgency Score Based on PRO-UC Daily e-Diary at Week 12	PRO-UC daily e-diary data was collected using a daily e-diary during the treatment period. Collection of the daily e-diary data was begun at least 10 days before the baseline visit. Participants were asked to record the signs and symptom data for number of bowel movement with urgency, as experienced over the previous 24 hours. Participant's signs and symptom average scores at each scheduled visit were calculated based on data recorded over the most recent 3 days (consecutive or nonconsecutive) of the last 10 days prior to the scheduled visit start date excluding the following days: day of any bowel preparation, day of endoscopy, any days between day of bowel preparation and day of endoscopy, and the 2 days after the day of endoscopy. Average number bowel movements urgency ranged from 0 to 27. Higher scores indicating more frequent bowel movements.	Baseline, Week 12
Secondary	Change From Baseline in Absolute Stool Frequency (Average Number of Bowel Movements) Score Based on PRO-UC Daily e-Diary at Week 12	PRO-UC daily e-diary data was collected using a daily e-diary during the treatment period. Collection of the daily e-diary data was begun at least 10 days before the baseline visit. Participants were asked to record the signs and symptom data for average number of bowel movements, as experienced over the previous 24 hours. Participant's signs and symptom average scores at each scheduled visit were calculated based on data recorded over the most recent 3 days (consecutive or nonconsecutive) of the last 10 days prior to the scheduled visit start date excluding the following days: day of any bowel preparation, day of endoscopy, any days between day of bowel preparation and day of endoscopy, and the 2 days after the day of endoscopy. Average number bowel movements ranged from 0 to 27. Higher scores indicating more frequent bowel movements.	Baseline, Week 12
Secondary	Change From Baseline in Absolute Rectal Bleeding (Average Number Bowel Movements With Blood) Score Based on PRO-UC Daily e-Diary at Week 12	PRO-UC daily e-diary data was collected using a daily e-diary during the treatment period. Collection of the daily e-diary data was begun at least 10 days before the baseline visit. Participants were asked to record the signs and symptom data for average number of bowel movements with blood, as experienced over the previous 24 hours. Participant's signs and symptom average scores at each scheduled visit were calculated based on data recorded over the most recent 3 days (consecutive or nonconsecutive) of the last 10 days prior to the scheduled visit start date excluding the following days: day of any bowel preparation, day of endoscopy, any days between day of bowel preparation and day of endoscopy, and the 2 days after the day of endoscopy. Average number bowel movements with blood ranged from 0 to 27. Higher scores indicating more frequent bowel movements.	Baseline, Week 12
Secondary	Change From Baseline in Total Sign/Symptom Score Based on PRO-UC Daily e-Diary at Week 12	Total sign/symptom score was the average of the average scores of worst abdominal pain over the past 24 hours and the conversion scale values for number of bowel movements blood, number of bowel movements with urgency, number of bowel movements and number of loose bowel movements, with scale ranged of 0-10, with higher scores indicating higher severity.	Baseline, Week 12
Secondary	Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Domains Scores at Weeks 8 and 12	IBDQ was a psychometrically validated participant-reported outcome (PRO) instrument for measuring the disease-specific health-related quality of life (HRQL) in participants with inflammatory bowel disease, including UC. The IBDQ consisted of 32 items, which were grouped into 4 domains: bowel function, emotional status, systemic symptoms, and social function The 4 domains were scored as follows: Bowel symptoms: 10 to 70; Systemic symptoms: 5 to 35; Emotional function: 12 to 84; Social function: 5 to 35. Higher scores indicating a better quality of life.	Baseline, Weeks 8 and 12
Secondary	Change From Baseline in IBDQ Total Scores at Weeks 8 and 12	IBDQ was a psychometrically validated PRO instrument for measuring the disease-specific HRQL in participants with inflammatory bowel disease, included UC. The IBDQ consisted of 32 items, which were grouped into 4 domains: bowel function, emotional status, systemic symptoms, and social function. The 4 domains were scored as follows: Bowel symptoms: 10 to 70; Systemic symptoms: 5 to 35; Emotional function: 12 to 84; Social function: 5 to 35. The total IBDQ score ranged from 32 to 224. For the total score and each domain, a higher score indicating better HRQL. A score of at least 170 corresponds to clinical remission and an increase of at least 16 points was considered to indicate a clinically meaningful improvement.	Baseline, Weeks 8 and 12
Secondary	Change From Baseline in Short Form-36 Health Survey (SF-36), Version 2, Acute (Physical and Mental Component Summary Scores) at Week 12	SF-36 was a generic quality-of-life instrument that had been widely used to assess health-related quality of life (HRQL) of participants). SF-36 consisted of 36 items that were aggregated into 8 multi-item scales (physical functioning [1=yes, limited a lot to 3=no, not limited at all], role-physical [1=all of the time to 5=none of the time], bodily pain [1=very severe to 6=none], general health [1=poor to 5=excellent], vitality [1=none of the time to 5=all of the time], social functioning [1=all of the time: to 5=none of the time], role emotional [1=all of the time to 5=none of the time] and mental health [1=all of the time to 5=none of the time]). Four domains comprised physical component summary (PCS) score (physical functioning, role-physical, bodily pain, general health) and remaining 4 domains comprised mental component summary (MCS) score (vitality, social functioning, role-emotional, mental health). The scores ranged from 0 to 100. Higher scores indicating better HRQL.	Baseline, Week 12
Secondary	Change From Baseline in Short Form-36 Health Survey (SF-36), Version 2, Acute (Individual Domain Scores) at Week 12	SF-36 was a generic quality-of-life instrument that had been widely used to assess HRQL of participants. The SF-36 consisted of 36 items that were aggregated into 8 multi-item scales (physical functioning [1=yes, limited a lot to 3=no, not limited at all], role-physical [1=all of the time to 5=none of the time], bodily pain [1=very severe to 6=none], general health [1=poor to 5=excellent], vitality [1=none of the time to 5=all of the time], social functioning [1=all of the time: to 5=none of the time], role emotional [1=all of the time to 5=none of the time] and mental health [1=all of the time to 5=none of the time]), with scores ranged from 0 to 100. Higher scores indicating better HRQL.	Baseline, Week 12
Secondary	Number of Participants Based on In-patient Hospitalization	Number of participants based on inpatient hospitalization due to all-cause hospitalization, gastrointestinal related, other illness/problem, and who had undergone gastrointestinal related procedures during the entire study period was reported.	Baseline up to Week 12
Secondary	Median Duration of Total In-patient Days	In-patient days were calculated as Date of discharge - Date of admission + 1. Median duration of total inpatient days during the entire study period was reported.	Baseline up to Week 12

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