A Study Of PF-00547659 In Patients With Moderate To Severe Ulcerative Colitis

Ulcerative Colitis Clinical Trial

— TURANDOT  

Official title:

A Double-blind, Randomized, Placebo-controlled, Parallel, Dose-ranging Study To Evaluate The Efficacy And Safety Of Pf-00547659 In Subjects With Moderate To Severe Ulcerative Colitis (Turandot)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01620255
• Other study ID #: A7281009
• Secondary ID: 2012-002030-37TU
• Status: Completed
• Phase: Phase 2
• Start date: November 2, 2012
• Est. completion date: February 4, 2016

Study information

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

Clinical Trial Summary

To determine the dose or doses of PF-00547659 that will be the most effective to improve or halt the disease symptoms in patients with moderate to severe ulcerative colitis.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 357
• Est. completion date: February 4, 2016
• Est. primary completion date: September 22, 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Subjects with diagnosis of Ulcerative Colitis for 3 or more months.
• Ulcerative colitis must be active beyond the rectum.
• Must active Ulcerative Colitis with a Total Mayo Score of 6 to 12 points

Exclusion Criteria:

• Pregnant or breast feeding.
• Diagnosis of indeterminate colitis or Crohn's Disease
• Subjects with history of colonic or small bowel obstruction or resection.

Related Conditions & MeSH terms

• Colitis
• Colitis, Ulcerative
• Ulcer
• Ulcerative Colitis

Intervention

Drug:
• Placebo
Placebo delivered subcutaneous injection, 3 doses separated by 4 weeks
• PF-00547659 SC Injection
Drug Dose Level 1 delivered subcutaneous injection, 3 doses separated by 4 weeks
• PF-00547659 SC Injection
Drug Dose Level 2 delivered subcutaneous injection, 3 doses separated by 4 weeks
• PF-00547659 SC Injection
Drug Dose Level 3 delivered subcutaneous injection, 3 doses separated by 4 weeks
• PF-00547659 SC Injection
Drug Dose Level 4 delivered subcutaneous injection, 3 doses separated by 4 weeks

Locations

Country	Name	City	State
Australia	Concord Repatriation General Hospital	Concord	New South Wales
Australia	The Canberra Hospital	Garran
Australia	Royal Brisbane and Women's Hospital	Herston	Queensland
Australia	Alfred Hospital	Melbourne	Victoria
Australia	The Royal Melbourne Hospital	Parkville	Victoria
Australia	Mater Health Services	South Brisbane	Queensland
Austria	AKH Wien, Universitaetsklinik fuer Innere Medizin III	Wien
Belgium	AZ St-Elisabeth Herentals	Herentals
Belgium	University Hospital Gasthuisberg	Leuven
Belgium	Centre Hospitalier de Mouscron	Mouscron
Bulgaria	4- MBAL	Sofia
Bulgaria	MBAL SofiaMed OOD	Sofia
Bulgaria	MBAL Sveti Ivan Rilski, Klinika po Gastroenterologia	Sofia
Canada	Hamilton Health Sciences Corporation, McMaster University Medical Centre	Hamilton	Ontario
Canada	McMaster University Medical Center	Hamilton	Ontario
Canada	London Health Sciences Centre - University Hospital	London	Ontario
Canada	Pavillion Rachel Tourigny, Hopital Maisonneuve-Rosemont	Montreal	Quebec
Canada	Oshawa Clinic	Oshawa	Ontario
Canada	Royal University Hospital	Saskatoon	Saskatchewan
Canada	GI Research Institute (GIRI)	Vancouver	British Columbia
Canada	Office of Dr. David C. Pearson	Victoria	British Columbia
Canada	Office of Drs. Ranjit Andrew Singh and Jamie D. Papp	Victoria	British Columbia
Canada	PerCuro Clinical Research Limited	Victoria	British Columbia
Czechia	Hepato-Gastroenterology HK s.r.o.	Hradec Kralove
Czechia	Klinické Centrum ISCARE I.V.F	Praha 7
Czechia	Krajska zdravotni, a.s., Masarykova nemocnice v Usti nad Labem o.z.	Usti nad Labem
France	CHU Amiens - Hôpital Nord	Amiens Cedex 01
France	Centre Hospitalier Universitaire (CHU) de Caen - Hopital Cote de Nacre	Caen
France	Hopital Huriez CHRU de Lille	Lille
France	Hôpital l'Archet 2 CHU de Nice	Nice Cedex 03
France	Hopital Haut Leveque	Pessac
France	Hôpital Nord Service de Gastro-entérologie	Saint Priest en Jarez
France	CHU Nancy - Hopital Brabois	Vandoeuvre les Nancy
Germany	Universitaetsklinikum Schleswig-Holstein, Campus Kiel	Kiel
Germany	Universitaetsklinik Regensburg	Regensburg
Germany	Robert-Bosch-Krankenhaus GmbH	Stuttgart
Hungary	Pannonia Maganorvosi Centrum Kft	Budapest
Hungary	Csongrad Megyei Dr. Bugyi Istvan Korhaz	Szentes
Israel	Digestive Disease Institute	Jerusalem
Israel	Gastroenterology and Liver Diseases Unit - Hadassah Ein Kerem University Hospital	Jerusalem
Israel	Dept. of Gastroenterology & Hepatology, Meir Medical Center	Kfar-Saba
Israel	Gastroenterology Division, Rabin Medical Center, Beilinson Campus	Petah Tikva
Israel	The Chaim Sheba Medical Center	Tel Hashomer
Italy	Universita' degli Studi "Magna Graecia" di Catanzaro, UO di Fisiopatologia Digestiva	Catanzaro
Italy	IBD Center - Divisione Gastroenterologia - Istituto Clinico Humanitas IRCCS	Milano
Italy	IRCCS Policlinico San Donato	Milano
Italy	Azienda Ospedaliera -Università di Padova	Padova
Italy	Azienda Ospedaliera Universitaria, Policlinico Tor Vergata	Roma
Italy	Policlinico Universitario Campus Bio-Medico	Roma
Italy	Universita Cattolica Sacro Cuore Policlinico "A. Gemelli"	Roma
Italy	AOS San Camillo Forlanini	Rome
Italy	Ospedale Casa Sollievo della Sofferenza	San Giovanni Rotondo
Korea, Republic of	Pusan National University Hospital	Busan
Korea, Republic of	Yeungnam University Hospital	Daegu
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Kangbuk Samsung Hospital	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Yonsei University College of Medicine, Severance Hospital	Seoul
Netherlands	Academic Medical Center - University of Amsterdam	Amsterdam	NH
Netherlands	University Medical Center Groningen (UMCG)	Groningen
Netherlands	Maastricht University Medical Center	Maastricht
New Zealand	Christchurch Hospital	Christchurch
New Zealand	Southern Endoscopy Centre	Christchurch
New Zealand	Cardiac Services Ltd.	Hamilton
New Zealand	Midland Neurology & EMG Ltd.	Hamilton
New Zealand	The Hamilton Eye Clinic	Hamilton
New Zealand	Waikato Hospital	Hamilton
Poland	Centrum endoskopii Zabiegowej, Poradnia Chorob Jelitowych,	Bydgoszcz
Poland	Gabinet Endoskopii Przewodu Pokarmowego	Krakow
Poland	Centrum Medyczne - Szpital Swietej Rodziny Sp. z o.o.	Lodz
Poland	Centrum Medyczne HCP Lecznictwo Ambulatoryjne Pracownia Endoskopowa	Poznan
Poland	Klinika Chorob Wewnetrznych i Gastroenterologii z Pododdzialem	Warszawa
Poland	NZOZ Vivamed	Warszawa
Poland	Lexmedica	Wroclaw
Poland	Wojskowy Szpital Kliniczny z Poliklinika SPOZ	Wroclaw
Russian Federation	SBEI of HPE North-West State Medical University n.a. I.I. Mechnikov of the MH of the RF St.P SBIH "	Saint-Petersburg
Serbia	Clinical Hospital Center Zemun, Gastroenterology and Hepatology Department	Belgrade
Serbia	Clinical Hospital Centre Bezanijska Kosa, Clinic for Internal medicine	Belgrade
Serbia	Clinical Hospital Centre Zvezdara Clinic for Gastroenterology and Hepatology	Belgrade
Serbia	Military medical Academy	Belgrade
Serbia	Clinical Centre of Nis, Clinic for Gastroenterology and Hepatology	Nis
Slovakia	Gastroenterological Centre Thalion	Bratislava
Slovakia	KM Management spol. s.r.o. Gastroenterologicke a hepatologicke centrum Nitra	Nitra
Slovakia	Gastro I., s.r.o.	Presov	Slovak Republic
Slovakia	Ustredna vojenska nemocnice SNP Ruzomberok	Ruzomberok
South Africa	Kingsbury Hospital	Claremont	Cape Town
Spain	Centro Medico Teknon	Barcelona
Spain	Hospital Clinic de Barcelona	Barcelona
Spain	Parc de Salut Mar-Hospital del Mar	Barcelona
Spain	Hospital Universitario Puerta de Hierro Majadahonda	Majadahonda	Madrid
United States	Albany Medical College	Albany	New York
United States	Georgia Endoscopy Center	Alpharetta	Georgia
United States	Florida Surgery Center	Altamonte Springs	Florida
United States	University of Michigan Health Systems	Ann Arbor	Michigan
United States	GI Consultants	Atlanta	Georgia
United States	Commonwealth Clinical Studies	Brockton	Massachusetts
United States	Signature Healthcare Brockton	Brockton	Massachusetts
United States	Department of Pharmacy Investigational Drug Services	Chapel Hill	North Carolina
United States	UNC Hospitals Endoscopy Center At Meadowmont	Chapel Hill	North Carolina
United States	UNC Memorial Hospital	Chapel Hill	North Carolina
United States	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina
United States	Surgery Center of Columbia	Columbia	Missouri
United States	Gastroenterology Associates	Crystal River	Florida
United States	Rocky Mountain Clinical Research, LLC.	Denver	Colorado
United States	Gastro One	Germantown	Tennessee
United States	East Valley Endoscopy	Grand Rapids	Michigan
United States	Endoscopy Center of Connecticut, LLC	Guilford	Connecticut
United States	Endoscopy Center of Connecticut, LLC	Hamden	Connecticut
United States	Gastroenterology Center of Connecticut, PC	Hamden	Connecticut
United States	Medical REsearch Center of CT Drug	Hamden	Connecticut
United States	Medical Research Network of Connecticut	Hamden	Connecticut
United States	Research Consultant Group	Hialeah	Florida
United States	Th Palmetto Surgery Center	Hialeah	Florida
United States	Baylor Clinic (Drug Storage)	Houston	Texas
United States	Baylor College Of Medicine - Baylor Medical Center	Houston	Texas
United States	Houston Hospital for Specialized Surgery	Houston	Texas
United States	Spring Gastroenterology and Associates	Humble	Texas
United States	Spring Gastroenterology Drug	Humble	Texas
United States	Covance Central Laboratory Services Inc	Indianapolis	Indiana
United States	Covance Central Laboratory Services, Inc	Indianapolis	Indiana
United States	Covance Laboratory Services, Inc	Indianapolis	Indiana
United States	Citrus Memorial Hospital	Inverness	Florida
United States	Inverness Medical Imaging	Inverness	Florida
United States	Nature Coast Clinical Research	Inverness	Florida
United States	Suncoast Endoscopy Center	Inverness	Florida
United States	Clinical and Translational Research Institute	La Jolla	California
United States	Perlman Medical Offices	La Jolla	California
United States	Thornton Hospital	La Jolla	California
United States	UCSD Health System-Pharmacy only	La Jolla	California
United States	Clinical Research of the Rockies	Lafayette	Colorado
United States	Las Vegas Surgery Center	Las Vegas	Nevada
United States	Steinberg Diagnostic Medical Imaging Centers	Las Vegas	Nevada
United States	University of Nevada School of Medicine (UNSOM)	Las Vegas	Nevada
United States	Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire
United States	University of Kentucky Chandler Medical Center	Lexington	Kentucky
United States	University of Kentucky Medical Center	Lexington	Kentucky
United States	Sand Lake Imaging	Maitland	Florida
United States	Diagnostic Imaging	Memphis	Tennessee
United States	Center for Digestive and Liver Diseases	Mexico	Missouri
United States	Coral View Surgery Center	Miami	Florida
United States	Sylvester Comprehensive Cancer Center	Miami	Florida
United States	University of Miami Hospital	Miami	Florida
United States	University of Miami Hospital and Clinic	Miami	Florida
United States	University of Miami Hospital and Clinic - Local Lab	Miami	Florida
United States	Center for Diagnostic Imaging	Miami Beach	Florida
United States	PI Radiology	Milwaukee	Wisconsin
United States	Minneapolis Medical Eye Clinic	Minneapolis	Minnesota
United States	Noran Neurology Clinic	Minneapolis	Minnesota
United States	First Quality Laboratory	Miramar	Florida
United States	FQL Research, LLC	Miramar	Florida
United States	Vanderbilt University Medical Center: Drug Shipment	Nashville	Tennessee
United States	Vanderbilt University Medical Center: Endoscopy Lab	Nashville	Tennessee
United States	Vanderbilt University Medical Center: GI Clinical Research	Nashville	Tennessee
United States	Vanderbilt University Medical Center: IBD Clinic	Nashville	Tennessee
United States	Vanderbilt University Medical Center: Outpatient Radiology	Nashville	Tennessee
United States	New York Presbyterian Hospital	New York	New York
United States	New York Presbyterian Hospital - Weill Cornell Medical College	New York	New York
United States	Weill Cornell Medical College - New York Presbyterian Hospital	New York	New York
United States	Weill Cornell Medical College of Cornell University	New York	New York
United States	Venutre Ambulatory Sugery Center	North Miami Beach	Florida
United States	Community Clinical Trials	Orange	California
United States	GastroDiagnostics - Community Clinical Trials Drug	Orange	California
United States	Boston Diagnostic Imaging	Orlando	Florida
United States	Citrus Ambulatory Surgery Center	Orlando	Florida
United States	Internal Medicine Specialists	Orlando	Florida
United States	Consulting Radiology	Plymouth	Minnesota
United States	Minneapolis Heart Institute	Plymouth	Minnesota
United States	Minnesota Gastroenterology, P.A.	Plymouth	Minnesota
United States	The Oregon Clinic, PC - Gastroenterology West	Portland	Oregon
United States	Premier Medical Group of the Hudson Valley, PC	Poughkeepsie	New York
United States	Premier Medical Group Research Department - Drug	Poughkeepsie	New York
United States	McGuire DVAMC	Richmond	Virginia
United States	Barnes-Jewish Hospital Investigational Drug Service (IP Shipping Address)	Saint Louis	Missouri
United States	Barnes-Jewish Hospital Radiology (X-Ray Only)	Saint Louis	Missouri
United States	Center for Advanced Medicine	Saint Louis	Missouri
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Mayo Clinic Arizona	Scottsdale	Arizona
United States	University of Washington	Seattle	Washington
United States	Texas Digestive Disease Consultants	Southlake	Texas
United States	Pioneer Research Solutions, Inc	Sugar Land	Texas
United States	Atlanta Gastroenterology Specialist	Suwanee	Georgia
United States	Rocky Mountain Gastroenterology Associates	Thornton	Colorado
United States	Endoscopic Microsurgery Associates	Towson	Maryland
United States	Allegiance Research Specialists	Wauwatosa	Wisconsin
United States	Dynacare Laboratories	Wauwatosa	Wisconsin
United States	GI associates drug	Wauwatosa	Wisconsin
United States	Shafran Gastroenterology Center	Winter Park	Florida
United States	Gastroenterology Associates of Western Michigan	Wyoming	Michigan
United States	Metro Health Endoscopy Unit	Wyoming	Michigan

Sponsors (1)

Lead Sponsor	Collaborator
Shire

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  Bulgaria,  Canada,  Czechia,  France,  Germany,  Hungary,  Israel,  Italy,  Korea, Republic of,  Netherlands,  New Zealand,  Poland,  Russian Federation,  Serbia,  Slovakia,  South Africa,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants in Clinical Remission at Week 12	Clinical remission was defined as a Total Mayo Score of less than or equal (<=) 2 points with no individual subscore exceeding 1 point and rectal bleed subscore of 0 or 1. The Mayo Score is a tool designed to measure disease activity for ulcerative colitis (UC). Scoring ranges from 0 to 12 points and consists of 4 subscores, each graded 0 to 3 with higher score indicating more severe disease activity. Endoscopic readings from the local and the central reader were considered for analysis. The central reading was used as the primary analysis and the local readings were used for the sensitivity analyses.	Week 12
Secondary	Percentage of Participants With Clinical Response at Week 12	Clinical response was defined as a decrease from baseline of at least 3 points in Total Mayo Score with at least a 30 percent (%) change, accompanied by at least 1 point decrease or absolute score of 0 or 1 in rectal bleeding subscore. The Mayo Score is a tool designed to measure disease activity for UC. Scoring ranges from 0 to 12 points and consists of 4 subscores, each graded 0 to 3 with higher score indicating more severe disease activity. Endoscopic readings from the local and the central reader were considered for analysis. The central reading was used as the primary analysis and the local readings were used for the sensitivity analyses.	Week 12
Secondary	Percentage of Participants With Mucosal Healing at Week 12	Mucosal healing was defined as absolute Mayo subscore for endoscopy of 0 or 1. The Mayo Score is a tool designed to measure disease activity for UC. Scoring ranges from 0 to 12 points and consists of 4 subscores, each graded 0 to 3 with higher score indicating more severe disease activity. Endoscopic readings from the local and the central reader were considered for analysis. The central reading was used as the primary analysis and the local readings were used for the sensitivity analyses.	Week 12
Secondary	Percentage of Participants With Absolute Partial Mayo Score of Less Than or Equal to (<=) 2 With no Individual Subscore More Than (>) 1 at Weeks 4, 8, and 12	An absolute Partial Mayo Score of <=2 corresponds to remission. However, this endpoint was incorrectly stated in the protocol and instead of "absolute Partial Mayo Score <=2", it was stated as "change from baseline in Partial Mayo Score <=2".	Weeks 4, 8, and 12
Secondary	Change From Baseline in Total Mayo Score at Week 12	The Mayo Score is a tool designed to measure disease activity for UC. Scoring ranges from 0 to 12 points and consists of 4 subscores, each graded 0 to 3 with higher score indicating more severe disease activity. Endoscopic readings from the local and the central reader were considered for analysis. The central reading was used as the primary analysis and the local readings were used for the sensitivity analyses.	Baseline, Week 12
Secondary	Percentage of Participants With Change From Baseline in Individual Mayo Subscores - Stool Frequency, Rectal Bleeding, and Physician's Global Assessment (PGA) - at Weeks 4, 8, and 12	The Mayo Score is a tool designed to measure disease activity for UC. Scoring ranges from 0 to 12 points and consists of 4 subscores (stool frequency, rectal bleeding, PGA, findings on flexible sigmoidoscopy), each graded 0 to 3 with higher score indicating more severe disease activity. Endoscopic readings from the local and the central reader were considered for analysis. The central reading was used as the primary analysis and the local readings were used for the sensitivity analyses. Changes from baseline in the subscore of less than (<) 0, 0, and >0 corresponded to improvement (imp), no change (NC), and worsening (wors) in that specific subscore.	Baseline; Weeks (W) 4, 8, and 12
Secondary	Percentage of Participants With Change From Baseline in Individual Mayo Subscore - Findings on Flexible Sigmoidoscopy - at Week 12	The Mayo Score is a tool designed to measure disease activity for UC. Scoring ranges from 0 to 12 points and consists of 4 subscores (stool frequency, rectal bleeding, PGA, findings on flexible sigmoidoscopy), each graded 0 to 3 with higher score indicating more severe disease activity. Endoscopic readings from the local and the central reader were considered for analysis. The central reading was used as the primary analysis and the local readings were used for the sensitivity analyses. Changes from baseline in the subscore of <0, 0, and >0 corresponded to improvement (imp), no change (NC), and worsening (wors) in that specific subscore.	Baseline, Week 12
Secondary	Percent Change From Baseline in Fecal Calprotectin at Weeks 4, 8, and 12	Fecal calprotectin was one of the pharmacodynamic (PD) biomarkers of the study.	Baseline, Weeks 4, 8, and 12
Secondary	Percent Change From Baseline in High Sensitivity C-reactive Protein (hsCRP) at Weeks 4, 8, and 12	hsCRP was one of the PD biomarkers of the study.	Baseline; Weeks 4, 8, and 12
Secondary	Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score at Week 12	IBDQ: Psychometrically validated patient reported outcome (PRO) instrument for measuring disease-specific quality of life (QOL) in participants with inflammatory bowel disease. IBDQ consists of 32 items, each item score ranged from 1 (worst possible response) to 7 (best possible response). Total score is the sum of each item score, ranged from 32 to 224 with higher score indicating better QOL. Positive change in total score indicated improvement in QOL.	Baseline, Week 12
Secondary	Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Domain Scores at Week 12	IBDQ: Psychometrically validated PRO instrument for measuring disease-specific QOL in participants with inflammatory bowel disease. IBDQ consists of 32 items, each item score ranged from 1 (worst possible response) to 7 (best possible response). Total score is the sum of each item score, ranged from 32 to 224 with higher score indicating better QOL. Positive change in total score indicated improvement in QOL. There are 4 individual domains under the IBDQ: bowel function (fx)/symptoms (score range of 10-70), systemic symptoms (score range of 5-35), emotional status/fx (score range of 12-84), and social fx (score range of 5-35). As with total score, higher scores indicate better QOL in that domain.	Baseline (BL), Week 12
Secondary	Percentage of Participants With an Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score of More Than or Equal to (>=) 170 at Week 12	IBDQ: Psychometrically validated PRO instrument for measuring disease-specific QOL in participants with inflammatory bowel disease. IBDQ consists of 32 items, each item score ranged from 1 (worst possible response) to 7 (best possible response). Total score is sum of each item score, ranged from 32 to 224 with higher score indicating better QOL. Positive change in total score indicated improvement in QOL. A score of >=170 corresponds to clinical remission.	Week 12
Secondary	Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Withdrawals Due to TEAEs During the Treatment Period (Weeks 0-12)	An adverse event (AE) was any untoward medical occurrence attributed to study drug in a participant who received study drug. TEAEs are defined as newly occurring AEs or those worsening after first dose. AEs comprised both SAEs and non-SAEs. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.	Screening through to end of treatment period, up to 12 weeks
Secondary	Maximum Serum PF-00547659 Concentration Achieved		Weeks 0 (baseline), 2, 4,8, 12, 16, 20, 24, 28, 32, and 36; Early Withdrawal

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