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

Ulcerative Colitis Clinical Trial

— FIGARO UC 302  

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 302)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03259308
• Other study ID #: SHP647-302
• Secondary ID: 2017-000572-28
• Status: Terminated
• Phase: Phase 3
• Start date: December 5, 2017
• Est. completion date: October 6, 2020

Study information

• Verified date: March 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 patient-reported symptoms and centrally read endoscopy, in participants with moderate to severe ulcerative colitis (UC).

Description:

27Mar2020: Enrollment of new patients into this study has been paused due to the COVID-19 situation. The duration of this pause is dependent on the leveling and control of the COVID-19 pandemic.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 279
• Est. completion date: October 6, 2020
• Est. primary completion date: July 15, 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 less than (<) 18 years of age must weigh >=40 kg and must have body mass index (BMI) >=16.5 kilogram per square metre (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:

a. A biopsy report to confirm the histological diagnosis. b. 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 ontamalimab (formerly PF-00547659, 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 (TB), general infections, heart failure, or malignancy.

• Participants with evidence of active or latent infection with Mycobacterium 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 TB 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 TB, 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 screening 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 HBcAb, the participant would be considered eligible if no presence of hepatitis B virus (HBV) DNA is confirmed by HBV DNA polymerase chain reaction (PCR) reflex testing performed in the central laboratory.

• Participants with chronic hepatitis C virus (HCV) (positive HCV antibody [HCVAb] and HCVRNA).

Note: Participants who are HCVAb positive without evidence of HCV RNA may be considered eligible (spontaneous viral clearance or previously treated and cured [defined as no evidence of HCVRNA 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 the 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 the study.

Related Conditions & MeSH terms

• Colitis
• Colitis, Ulcerative
• Ulcer
• Ulcerative Colitis

Intervention

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

Locations

Country	Name	City	State
Argentina	Fundación Favaloro	Buenos Aires
Argentina	Hospital Privado Centro Médico de Córdoba	Córdoba
Argentina	Sanatorio 9 de Julio SA	San Miguel de Tucumán	Tucumán
Belgium	UZ Gent	Gent	Oost-Vlaanderen
Belgium	AZ Groeninge	Kortrijk	West-Vlaanderen
Belgium	UZ Gasthuisberg	Leuven	Vlaams Brabant
Belgium	CHU Mouscron	Mouscron
Bosnia and Herzegovina	Clinical Center Banja Luka	Banja Luka
Bulgaria	University Multiprofile Hospital for Active Treatment - Dr. Georgi Stranski EAD	Pleven
Bulgaria	Multiprofile Hospital for Active Treatment Eurohospital	Plovdiv
Bulgaria	Specialized Hospital for Active Treatment of Pneumophthisiatric Diseases Dr.D.Gramatikov- Ruse- PPDS	Ruse
Bulgaria	Medical Center-1-Sevlievo EOOD	Sevlievo
Bulgaria	Acibadem City Clinic University Multiprofile Hospital for Active Treatment EOOD	Sofia	Sofia-Grad
Bulgaria	Diagnostic and Consulting Center Aleksandrovska EOOD	Sofia	Sofia-Grad
Bulgaria	Medical Center Convex EOOD	Sofia
Bulgaria	Medical Center Excelsior OOD - PPDS	Sofia
Bulgaria	Second Multiprofile Hospital for Active Treatment Sofia	Sofia	Sofia-Grad
Bulgaria	University Multiprofile Hospital for Active Treatment Sv Ivan Rilski EAD	Sofia
Bulgaria	University Multiprofile Hospital for Active Treatment Sveta Anna	Sofia	Sofia-Grad
Bulgaria	University Multiprofile Hospital for Active Treatment Tsaritsa Yoanna - ISUL EAD	Sofia
Bulgaria	Diagnostic Consultative Centre Mladost - M OOD	Varna
Canada	Toronto Digestive Disease Associates Inc	Toronto	Ontario
Canada	Percuro Clinical Research LTD	Victoria	British Columbia
Colombia	Fundación Clínica Shaio	Bogota	Cundinamarca
Colombia	Servimed S.A.S	Bucaramanga	Santander
Colombia	IPS Centro Médico Julián Coronel S.A.S. - PPDS	Cali
Colombia	Hospital Pablo Tobón Uribe	Medellin	Antioquia
Estonia	East Viru Central Hospital	Kohta-Järve
Estonia	OÜ LV Venter	Parnu
Estonia	West Tallinn Central Hospital	Tallinn
Greece	Ippokrateio General Hospital of Athens	Athens	Attiki
Greece	University General Hospital of Patras	Patras
Greece	Euromedica - PPDS	Thessaloniki
Greece	Theageneio Anticancer Oncology Hospital of Thessaloniki	Thessaloniki
Hungary	Bekes Megyei Kozponti Korhaz	Bekescsaba
Hungary	ENDOMEDIX Kft.	Budapest
Hungary	Magyar Honvédség Egészségügyi Központ	Budapest
Hungary	Pannónia Magánorvosi Centrum Kft	Budapest
Hungary	Debreceni Egyetem Klinikai Kozpont	Debrecen
Hungary	Bekes Megyei Kozponti Korhaz	Gyula
Hungary	Mohacsi Korhaz	Mohacs
Hungary	Fejer Megyei Szent Gyorgy Egyetemi Oktato Korhaz	Székesfehérvár
Hungary	Tolna Megyei Balassa János Kórház	Szekszard
Hungary	Csongrad Megyei Dr. Bugyi Istvan Korhaz	Szentes
Hungary	Jávorszky Ödön Kórház	Vác
Hungary	Csolnoky Ferenc Korhaz	Veszprém
Ireland	St Vincent's University Hospital	Dublin
Japan	Kunimoto Hospital	Asahikawa
Japan	Fukuoka University Chikushi Hospital	Chikushino
Japan	Medical Corporation Aoyama Clinic	Kobe-shi	Hyôgo
Japan	Aizawa Hospital	Matsumoto-shi
Japan	Hyogo College of Medicine	Nishinomiya-shi	Hyôgo
Japan	Ishida Clinic of IBD and Gastroenterology	Oita
Japan	Chiinkai Dojima General & Gastroenterology Clinic	Osaka
Japan	Yodogawa Christian Hospital	Osaka
Japan	Kinshukai Infusion Clinic	Osaka-shi
Japan	Bellland General Hospital	Sakai
Japan	Toho University Sakura Medical Center	Sakura
Japan	Sapporo Medical University Hospital	Sapporo	Hokkaidô
Japan	Tohoku Rosai Hospital	Sendai
Japan	Dokkyo Medical University Hospital	Shimotsuga-gun
Japan	Medical Corporation Shoyu-kai Fujita Gastroenterology Hospital	Takatsuki
Japan	Koukokukai Ebisu Clinic	Tokyo
Japan	Nihonbashi Egawa Clinic	Tokyo
Korea, Republic of	Inje University Haeundae Paik Hospital	Busan
Korea, Republic of	Pusan National University Hospital	Busan
Korea, Republic of	Kyungpook National University Chilgok Hospital	Daegu
Korea, Republic of	Kyungpook National University Hospital	Daegu
Korea, Republic of	Yeungnam University Hospital	Daegu
Korea, Republic of	Gachon University Gil Medical Center	Incheon
Korea, Republic of	CHA Bundang Medical Center, CHA University	Seongnam	Gyeonggido
Korea, Republic of	Asan Medical Center - PPDS	Seoul
Korea, Republic of	Inje University Seoul Paik Hospital	Seoul
Korea, Republic of	Kangbuk Samsung Hospital	Seoul
Korea, Republic of	Kyung Hee University Hospital	Seoul
Korea, Republic of	Samsung Medical Center PPDS	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Severance Hospital Yonsei University Health System - PPDS	Seoul
Korea, Republic of	The Catholic University of Korea, St. Vincent's Hospital	Suwon	Gyeonggido
Korea, Republic of	Yonsei University Wonju Severance Christian Hospital	Wonju-si	Gang'weondo
Lebanon	Rafik Hariri University Hospital	Beirut
Lebanon	Hammoud Hospital University Medical Center	Saida
Mexico	Centro de Investigación Médica Aguascalientes	Aguascalientes
Mexico	Health Pharma Professional Research S.A de C.V.	Ciudad de Mexico	Distrito Federal
Mexico	Phylasis Clinicas Research S. de R.L. de C.V.	Cuautitlan Izcalli
Mexico	Clinica de Higado y Gastroenterologia Integral, S.C.	Cuernavaca	Morelos
Mexico	JM Research S.C	Cuernavaca	Morelos
Mexico	Centro de Investigacion Clinica Acelerada, S.C.	Distrito Federal
Mexico	Instituto de Investigaciones Aplicadas a la Neurociencia A.C.	Durango
Mexico	Unidad de Atencion Medica e Investigacion en Salud	Merida	Yucatán
Mexico	Accelerium, S. de R.L. de C.V.	Monterrey
Mexico	Clinical Research Institute	Tlalnepantla De Baz
Mexico	Investigacion Biomedica para el Desarrollo de Farmacos S.A. de C.V.	Zapopan, Jalisco
New Zealand	Dunedin Hospital	Dunedin	South Island
New Zealand	Auckland City Hospital	Grafton	Auckland
New Zealand	Waikato Hospital	Hamilton
New Zealand	Wellington Hospital	Newtown	Wellington
Portugal	Hospital de Braga	Braga
Portugal	Hospital Senhora da Oliveira - Guimaraes, E.P.E	Guimarães
Portugal	Hospital da Luz	Lisboa
Portugal	Centro Hospitalar do Algarve - Hospital de Portimao	Portimão
Portugal	Hospital de São Bernardo	Setubal
Slovakia	Univerzitna nemocnica Bratislava	Bratislava
Slovakia	KM Management, spol. s r.o.	Nitra
Slovakia	Gastro LM, s.r.o.	Presov
Spain	Centro Medico Teknon - Grupo Quironsalud	Barcelona
Spain	C.H. Regional Reina Sofia - PPDS	Cordoba	Córdoba
Spain	Hospital Universitario de Fuenlabrada	Fuenlabrada	Madrid
Spain	Hospital Universitario Juan Ramon Jimenez	Huelva
Spain	Hospital Universitario de La Princesa	Madrid
Spain	Hospital Universitario Fundacion Jimenez Diaz	Madrid
Spain	Hospital Universitario La Paz - PPDS	Madrid
Spain	Hospital Universitario Virgen del Rocio - PPDS	Sevilla
Spain	Hospital Universitari i Politecnic La Fe de Valencia	Valencia
Spain	CHUVI - H.U. Alvaro Cunqueiro	Vigo	Pontevedra
Switzerland	Universität Zürich	Zürich	Zürich (de)
Turkey	Istanbul Universitesi Cerrahpasa Tip Fakultesi	Istanbul
Turkey	Mersin University Medical Faculty	Mersin
Ukraine	Regional Municipal Non-profit Enterprise "Chernivtsi Regional Clinical Hospital"	Chernivtsi	Chernivets'ka Oblast
Ukraine	LLC Medical Center Family Medicine Clinic	Dnipro
Ukraine	ME Dnipropetrovsk Regional Clinical Hospital n.a. I.I Mechnykov Dnipropetrovsk Regional Council	Dnipro
Ukraine	State Institution "Institute of Gastroenterology of National Academy of Medical Sciences of Ukraine"	Dnipro
Ukraine	Clinic of SI National Institute of Therapy n.a. L.T. Mala of NAMS of Ukraine	Kharkiv
Ukraine	Communal Non-Commercial Enterprize of Kharkiv Regional Council Regional Clinical Hospital	Kharkiv
Ukraine	MNPE of Kharkiv Regional Council Regional Clinical Specialized Dispensary of Radiation Protection	Kharkiv
Ukraine	Municipal Nonprofit Enterprise CCH #2 n.a. prof. O.O. Shalimov of Kharkiv City Council	Kharkiv	Kharkivs'ka Oblast
Ukraine	Municipal Non-profit Enterprise Kherson City Clinical Hospital named after Ye.Ye. Karabelesh	Kherson
Ukraine	Municipal Enterprise Kryvyi Rih City Clinical Hospital #2 of Kryvyi Rih City Council	Kryvyi Rih
Ukraine	Kyiv City Clinical Hospital #18	Kyiv
Ukraine	Medical Center of LLC Medical Clinic Blagomed	Kyiv
Ukraine	Municipal Institution of KRC Kyiv Regional Hospital #2	Kyiv
Ukraine	Municipal Non-profit Enterprise of Kyiv Regional Council Kyiv Regional Clinical Hospital	Kyiv
Ukraine	Treatment and Diagnostic Center "Healthy and Happy" of LLC "Healthy and Happy"	Kyiv
Ukraine	Lviv Railway Clinical Hospital of branch Health Center of Joint Stock Co. Ukrainian Railway	Lviv
Ukraine	Municipal Nonprofit Enterprise Lviv Clinical Emergency Care Hospital	Lviv
Ukraine	Municipal Non-profit Enterprise Odessa Regional Clinical Hospital of Odessa Regional Council	Odesa
Ukraine	MNPE Central City Clinical Hospital of Uzhhorod City Council	Uzhhorod
Ukraine	City Clinical Hospital #1	Vinnytsia
Ukraine	Communal Non-Commercial Enterprise "Vinnytsia City Clinical Hospital ?1"	Vinnytsia
Ukraine	Communal Nonprofit Enterprise Vinnytsia Regional Clinical Hospital named after N.I. Pirogov VRC	Vinnytsia
Ukraine	Communal Nonprofit Enterprise Vinnytsia Regional Clinical Hospital named after N.I. Pirogov VRC	Vinnytsia	Vinnyts'ka Oblast
Ukraine	Medical Clinical Research Center of Medical Center LLC Health Clinic	Vinnytsia
Ukraine	Municipal Nonprofit Enterprise Vinnytsia City Clinical Hospital #1	Vinnytsya	Vinnyts'ka Oblast
Ukraine	MNPE City Hospital No. 6 of Zaporizhzhia City Council	Zaporizhzhia
Ukraine	Municipal Non-profit Enterprise City Emergency Care Hospital of Zaporizhzhia Regional Council	Zaporizhzhia
United States	Advanced Research Center	Anaheim	California
United States	University of Michigan	Ann Arbor	Michigan
United States	Infinite Clinical Trials	Atlanta	Georgia
United States	Commonwealth Clinical Studies LLC	Brockton	Massachusetts
United States	Renaissance Research Medical Group, INC	Cape Coral	Florida
United States	Clinical Research Institute of Michigan	Chesterfield	Michigan
United States	Chevy Chase Clinical Research	Chevy Chase	Maryland
United States	Loretto Hospital	Chicago	Illinois
United States	Gastro Florida	Clearwater	Florida
United States	Hi Tech and Global Research, LLc	Coral Gables	Florida
United States	Kindred Medical Institute for Clinical Trials, LLC	Corona	California
United States	Atlanta Center For Gastroenterology PC	Decatur	Georgia
United States	United Medical Doctors	Encinitas	California
United States	Prestige Clinical Research	Franklin	Ohio
United States	Mid Atlantic Health Specialists	Galax	Virginia
United States	Digestive Health Associates of Texas, P.A.dba DHAT Research Institute	Garland	Texas
United States	NYU Langone Long Island Clinical Research Associates	Great Neck	New York
United States	IL Gastroenterology Group	Gurnee	Illinois
United States	National Clinical, LLC	Hamtramck	Michigan
United States	Gastroenterology Associates of Hazard	Hazard	Kentucky
United States	Edward Hines Jr VA Hospital - NAVREF - PPDS	Hines	Illinois
United States	CroNOLA, LLC.	Houma	Louisiana
United States	Aztec Medical Research	Houston	Texas
United States	BI Research Center	Houston	Texas
United States	Biopharma Informatic Inc.	Houston	Texas
United States	Precision Research Institute, LLC	Houston	Texas
United States	Southwest Clinical Trials	Houston	Texas
United States	East Carolina Gastroenterology	Jacksonville	North Carolina
United States	ENCORE Borland-Groover Clinical Research - ERN - PPDS	Jacksonville	Florida
United States	SIH Research	Kissimmee	Florida
United States	Mayo Clinic Health System - PPDS	La Crosse	Wisconsin
United States	University of California San Diego	La Jolla	California
United States	Advanced Biomedical Research of America	Las Vegas	Nevada
United States	Alliance Medical Research LLC	Lighthouse Point	Florida
United States	VA Long Beach Healthcare System - NAVREF - PPDS	Long Beach	California
United States	Ohio Clinical Research Partners LLC	Mentor	Ohio
United States	Arizona Digestive Health Mesa - East	Mesa	Arizona
United States	Sanchez Clinical Research, Inc	Miami	Florida
United States	Crystal Biomedical Research	Miami Lakes	Florida
United States	Facey Medical Foundation	Mission Hills	California
United States	United Medical Doctors	Murrieta	California
United States	Pharma Research International Inc	Naples	Florida
United States	Bayside Clinical Research - New Port Richey	New Port Richey	Florida
United States	Weill Cornell Medical College	New York	New York
United States	Encompass Care	North Las Vegas	Nevada
United States	Dupage Medical Group	Oakbrook Terrace	Illinois
United States	Veteran's Research and Education Foundation - NAVREF - PPDS	Oklahoma City	Oklahoma
United States	Southtowns Gastroenterology, PLLC	Orchard Park	New York
United States	Elite Clinical Studies - Phoenix - Clinedge - PPDS	Phoenix	Arizona
United States	Accel Research Sites - St. Petersburg - ERN - PPDS	Pinellas Park	Florida
United States	Veterans Research Foundation of Pittsburgh - NAVREF - PPDS	Pittsburgh	Pennsylvania
United States	BRCR Medical Center Inc.	Plantation	Florida
United States	Alliance Clinical Research-(Vestavia Hills)	Poway	California
United States	St Louis Center For Clinical Research	Saint Louis	Missouri
United States	Washington University in St. Louis	Saint Louis	Missouri
United States	Southern Star Research Institute LLC	San Antonio	Texas
United States	University of California San Francisco	San Francisco	California
United States	Care Access Research, San Pablo	San Pablo	California
United States	Atlanta Gastroenterology Specialists, PC	Suwanee	Georgia
United States	DBC Research	Tamarac	Florida
United States	Winchester Gastroenterology Associates	Winchester	Virginia
United States	UMass Memorial Medical Center	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Shire

Countries where clinical trial is conducted

United States,  Argentina,  Belgium,  Bosnia and Herzegovina,  Bulgaria,  Canada,  Colombia,  Estonia,  Greece,  Hungary,  Ireland,  Japan,  Korea, Republic of,  Lebanon,  Mexico,  New Zealand,  Portugal,  Slovakia,  Spain,  Switzerland,  Turkey,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Remission Based on Composite Score 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 derived from 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 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. The stool frequency sub-score and rectal bleeding sub-score ranged from 0 to 3 with higher scores indicating 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. Number of participants with mucosal healing based on endoscopic and histological assessment using the Geboes score grading system were reported.	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, at the Week 12. 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	Number of participants were reported with stool frequency sub-scores of 0 or 1 and rectal bleeding sub-score of 0. 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. The stool frequency sub-score and rectal bleeding sub-score of Mayo score ranges from 0 to 3 with higher scores indicating 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	Number of participants were reported with rectal bleeding and stool frequency sub-scores of 0. Clinical remission was defined as both rectal bleeding and stool frequency sub-scores of 0. The stool frequency sub-score and rectal bleeding sub-score of Mayo score ranges from 0 to 3 with higher scores indicating 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 signs and symptom data were collected using a daily e-diary during treatment period. Collection of 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 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. 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 the 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 signs and symptom data were collected using a daily e-diary during treatment period. Collection of 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 signs and symptom data were collected using a daily e-diary during treatment period. Collection of 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 signs and symptom data were collected using a daily e-diary during treatment period. Collection of 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 signs and symptom data were collected using a daily e-diary during treatment period. Collection of 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 with blood.	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 dimensions: 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 dimensions: 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. Generic instruments were used in general populations to assess a wide range of domains applicable to a variety of health states, conditions, and diseases. 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 Inpatient Hospitalization	Number of participants based on inpatient hospitalization due to all-cause hospitalization, gastrointestinal related, other illness/problem, and undergo gastrointestinal related procedures during the entire study period were reported.	From start of study up to follow up (Week 29)
Secondary	Median Duration of Total Inpatient Days	Inpatient days were calculated as Date of discharge - Date of admission + 1. Median duration of total inpatient days during the entire study period was reported.	From start of study up to follow-up (Week 29)

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