Long-Term Safety Of PF-00547659 In Ulcerative Colitis (TURANDOT II)

A Multicenter Open-Label Extension Study To Assess Long-Term Safety Of PF-00547659 In Subjects With Ulcerative Colitis (TURANDOT II)

Subjects with Ulcerative Colitis who have completed an induction study with PF-00547659 will receive an additional 144 weeks of open-label treatment to evaluate the long-term safety of the drug.

Study Overview

• Status: Completed
• Conditions: Ulcerative Colitis
• Intervention / Treatment: Drug: 75mg SHP647 (PF-00547659); Drug: 225mg SHP647 (PF-00547659)

• Study Type: Interventional
• Enrollment (Actual): 330
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Australian Capital Territory
    • Garran, Australian Capital Territory, Australia, 2605
      • The Canberra Hospital
  • New South Wales
    • Concord, New South Wales, Australia, 2139
      • Concord Repatriation General Hospital
  • Queensland
    • Herston, Queensland, Australia, 4029
      • Royal Brisbane and Women's Hospital
    • South Brisbane, Queensland, Australia, 4101
      • Mater Health Services
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • Alfred Hospital
    • Parkville, Victoria, Australia, 3052
      • The Royal Melbourne Hospital
• Austria
  • Wien, Austria, 1090
    • AKH Wien, Universitaetsklinik fuer Innere Medizin III
• Belgium
  • Herentals, Belgium, 2200
    • AZ St. Elisabeth Herentals
  • Leuven, Belgium, 3000
    • University Hospital Gasthuisberg
  • Mouscron, Belgium, 7700
    • Centre Hospitalier De Mouscron
• Bulgaria
  • Sofia, Bulgaria, 1431
    • MBAL Sveti Ivan Rilski, Klinika po Gastroenterologia
• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V6Z 2K5
      • (G.I.R.I.) GI Research Institute
    • Victoria, British Columbia, Canada, V8V 3P9
      • Percuro Clinical Research, Ltd
  • Ontario
    • Hamilton, Ontario, Canada, L8S 4K1
      • Hamilton Health Sciences Corp, McMaster Univ Medical Centre
    • London, Ontario, Canada, N6A 5A5
      • London Health Sciences Centre - University Hospital
    • Oshawa, Ontario, Canada, L1H 7K4
      • Taunton Surgical Centre
  • Quebec
    • Montreal, Quebec, Canada, H1T 2M4
      • Universite de Montreal - Hopital Maisonneuve-Rosemont (HMR)
  • Saskatchewan
    • Saskatoon, Saskatchewan, Canada, S7N 0W8
      • Royal University Hospital
• Czechia
  • Hradec Kralove, Czechia, 50012
    • Hepato-Gastroenterologie HK s.r.o. Poliklinika III
  • Prague, Czechia, 170 04
    • IBD Clinical and Research centre
  • Usti nad Labem, Czechia, 401 13
    • Krajská zdravotní, a.s., Masarykova nemocnice v Ústí nad Labem
• France
  • Amiens, France, 80054
    • CHU Amiens-Picardie - Hopital Sud
  • Caen, France, 14033
    • Centre Hospitalier Universitaire (CHU) de Caen - Hopital Cote de Nacre
  • Lille, France, 59037 Cedex
    • Hopital Huriez CHRU de Lille
  • Nice Cedex 03, France, 06200
    • CHU De Nice Hopital De L'Archet II
  • Saint Priest En Jarez, France, 42270
    • CHU de Saint-Etienne Hôpital Nord
  • Vandoeuvre les Nancy, France, 54511
    • CHU de Nancy - Hôpital Brabois
• Germany
  • Regensburg, Germany, 93053
    • Universitaetsklinikum Regensburg, Klinik und Poliklinik fuer Innere Medizin 1
  • Schleswig-Holstein
    • Kiel, Schleswig-Holstein, Germany, 24105
      • Universitaetsklinikum Schleswig-Holstein, Campus Kiel
• Hungary
  • Csongrad
    • Szentes, Csongrad, Hungary, 6600
      • Csongrád Megyei Dr. Bugyi István Kórház
• Israel
  • Jerusalem, Israel, 91031
    • Shaare Zedek Medical Center
  • Jerusalem, Israel, 91120
    • Hadassah Ein Kerem University Hospital - Gastroenterology and Liver Diseases Unit
  • Kfar-Saba, Israel, 44281
    • Meir Medical Center
  • Tel Hashomer, Israel, 5262000
    • The Chaim Sheba Medical Center
• Italy
  • Catanzaro, Italy, 88100
    • Universita' degli Studi "Magna Graecia" di Catanzaro
  • Milano, Italy, 20089
    • Milan University, Humanitas Clinical Institute
  • Roma, Italy, 00168
    • Università Cattolica del Sacro Cuore
  • Roma, Italy, 00128
    • Policlinico Universitario Campus Bio-Medico
  • Roma, Italy, 00133
    • Azienda Ospedaliera Universitaria, Policlinico Tor Vergata
  • Roma, Italy, 00152
    • Azienda Ospedaliera San Camillo Forlanini
  • San Giovanni Rotondo, Italy, 71013
    • Ospedale Casa Sollievo della Sofferenza
• Korea, Republic of
  • Daegu, Korea, Republic of, 42415
    • Yeungnam University Medical Center
  • Seoul, Korea, Republic of, 135-710
    • Samsung Medical Center
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 05505
    • Asan Medical Center
  • Seoul, Korea, Republic of, 03181
    • Kangbuk Samsung Hospital
• Netherlands
  • Amsterdam, Netherlands, 1105 AZ
    • Academic Medical Center
  • Groningen, Netherlands, 9713 GZ
    • University Medical Center Groningen (UMCG)
  • Maastricht, Netherlands, 6229 HX
    • Maastricht University Medical Center
• New Zealand
  • Hamilton, New Zealand, 3240
    • Waikato Hospital
  • Canterbury
    • Christchurch, Canterbury, New Zealand, 8140
      • Christchurch Hospital
• Poland
  • Krakow, Poland, 31-009
    • Gabinet Endoskopii Przewodu Pokarmowego
  • Poznan, Poland, 61-485
    • NZOZ Centrum Medyczne HCP sp. z o.o
  • Warszawa, Poland, 02-507
    • Klinika Chorob Wewnetrznych I Gastroenterologii
  • Warszawa, Poland, 03-580
    • Niepubliczny Zaklad Opieki Zdrowotnej VIVAMED
  • Wroclaw, Poland, 53-114
    • LexMedica
  • Kujawsko-Pomorskie
    • Bydgoszcz, Kujawsko-Pomorskie, Poland, 85-168
      • Centrum Endoskopii Zabiegowej
  • Wojlodzkie
    • Lodz, Wojlodzkie, Poland, 90-302
      • Centrum Medyczne-Szpital Swietej Rodziny Sp.z.o.o.
• Russian Federation
  • Saint-Petersburg, Russian Federation, 191015
    • St. Petersburg State Medical Academy for Postgraduate Education
• Serbia
  • Belgrade, Serbia, 11000
    • Military Medical Academy
  • Belgrade, Serbia, 11080
    • Clinical Hospital Center Zemun
  • Belgrade, Serbia, 11080
    • Clinical Hospital Centre Bezanijska Kosa
• Slovakia
  • Nitra, Slovakia, 949 01
    • Ustredna vojenska nemocnica SNP Ruzomberok - Fakultna nemocnica
  • Presov, Slovakia, 080 01
    • Gastro L., s.r.o.
  • Ruzomberok, Slovakia, 034 26
    • Ustredna vojenska nemocnice SNP Ruzomberok - Fakultna nemocnica
• South Africa
  • Cape Town
    • Claremont, Cape Town, South Africa, 7708
      • Kingsbury Hospital
• Spain
  • Barcelona, Spain, 08036
    • Hospital Clinic De Barcelona
  • Barcelona, Spain, 08022
    • Centro Medico Teknon-Institut de la Macula i de la Retina
  • Barcelona, Spain, 8003
    • Parc de Salut Mar-Hospital del Mar
  • Madrid
    • Majadahonda, Madrid, Spain, 28222
      • Hospital Universitario Puerta de Hierro
• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85259
      • Mayo Clinic Arizona - Scottsdale
  • California
    • La Jolla, California, United States, 92093
      • UCSD Altman Clinical and Translational Research Institute
    • Orange, California, United States, 92868
      • Community Clinical Trials
  • Colorado
    • Thornton, Colorado, United States, 80229
      • Rocky Mountain Gastroenterology
  • Connecticut
    • Hamden, Connecticut, United States, 06518
      • Medical Research Center of Connecticut, LLC
  • Florida
    • Inverness, Florida, United States, 34452
      • Nature Coast Clinical Research
    • Miramar, Florida, United States, 33025
      • Bassan and Bloom M.D.s
    • Orlando, Florida, United States, 32806
      • Internal Medicine Specialists
    • Winter Park, Florida, United States, 32789
      • Shafran Gastroenterology Center
  • Georgia
    • Suwanee, Georgia, United States, 30024
      • Atlanta Gastroenterology Specialists, PC
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • University of Kentucky Medical Center
  • Massachusetts
    • Brockton, Massachusetts, United States, 02302
      • Commonwealth Clinical Studies
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
  • Minnesota
    • Plymouth, Minnesota, United States, 55446
      • Minnesota Gastroenterology, PA
  • Missouri
    • Mexico, Missouri, United States, 65265
      • Center for Digestive and Liver Diseases
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • Nevada
    • Las Vegas, Nevada, United States, 89102
      • University of Nevada School of Medicine
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Dartmouth Hitchcock Medical Center
  • New York
    • Albany, New York, United States, 12208
      • Albany Medical College
    • New York, New York, United States, 10021
      • Weill Cornell Medical College of Cornell University
    • Poughkeepsie, New York, United States, 12601
      • Premier Medical Group of the Hudson Valley, PC
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • UNC Memorial Hospital
  • Oregon
    • Portland, Oregon, United States, 97225
      • The Oregon Clinic-West Hills Gastroenterology Associates, P.C.
  • Tennessee
    • Germantown, Tennessee, United States, 38138
      • Gastro One
    • Nashville, Tennessee, United States, 37212
      • Vanderbilt University Medical Center
  • Texas
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine - Baylor Medical Center
  • Virginia
    • Richmond, Virginia, United States, 23249
      • McGuire DVAMC
  • Washington
    • Seattle, Washington, United States, 98195
      • Univeristy of Washington
  • Wisconsin
    • Wauwatosa, Wisconsin, United States, 53226
      • Allegiance Research Specialists

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 66 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subjects between 18 and 66 years of age.
• Subjects previously enrolled in study A7281009 (NCT01620255) who have completed the 84 day (12 week) induction period.

Exclusion Criteria:

• Subjects that have completed Day 84 (Week 12) of study A7281009 but have experienced serious event(s) related to the investigational product, an unstable medical condition, or any other reason, in the opinion of the investigator, would preclude entry or participation in this study.
• Subjects who are taking any dose of Azathioprine (AZA), 6-mercaptopurine(6 MP) or Methotrexate (MTX).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SHP647 75 mg; Participants will receive 75 milligrams (mg) of SHP647 subcutaneous (SC) injection every 4 weeks for 72 weeks in the anterolateral right/left thigh or the deltoid area or the abdomen. During the first 72 weeks, a one time dose escalation to 225 mg of SHP647 SC injection every 4 weeks is allowed after 8 weeks of the study for participants who experience clinical deterioration or unacceptably low level of response to the investigational product. The decision to escalate will be guided by the response and relapse criteria tempered by clinical judgment. Following the first 72 weeks, participants will receive 75 mg of SHP647 SC injection every 4 weeks for an additional 72 weeks in the anterolateral right/left thigh or the deltoid area or the abdomen.	Drug: 75mg SHP647 (PF-00547659); 75 mg sterile liquid injected subcutaneously every 4 weeks.
Experimental: SHP647 225 mg; Participants will receive 225 mg of SHP647 SC injection every 4 weeks for 72 weeks followed by 75 mg of SHP647 SC injection every 4 weeks for an additional 72 weeks in the anterolateral right/left thigh or the deltoid area or the abdomen.	Drug: 225mg SHP647 (PF-00547659); 225 mg sterile liquid injected subcutaneously every 4 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs), and Who Withdrew From Treatment Due to Treatment-Emergent Adverse Events (TEAEs)	An adverse event (AE) was defined as any untoward medical occurrence in a clinical investigation participant who was administered a product or medical device; the event did not need to necessarily have a causal relationship with the treatment or usage. A serious adverse event (SAE) was any untoward medical occurrence at any dose that resulted in death, was life threatening (immediate risk of death), required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, resulted in congenital anomaly/birth defect. Number of participants with TEAEs, STEAEs, and those withdrew from treatment due to TEAEs were reported.	From start of study drug administration up to 168 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Mucosal Healing at Week 16	Mucosal healing was defined as an absolute Mayo subscore for endoscopy of 0 or 1 (based on centrally read score) as assessed by flexible sigmoidoscopy or colonoscopy. The Mayo score is a tool designed to measure disease activity for ulcerative colitis (UC). The Mayo scoring system ranges from 0 to 12 points and consists of 4 subscores (stool frequency, rectal bleeding, findings on flexible sigmoidoscopy, and physician's global assessment [PGA]) each graded 0 to 3 with the higher score indicating more severe disease activity. The percentage of participants with mucosal healing at week 16 was reported.	Week 16
Serum Trough Concentrations of SHP647 Versus Time	Serum trough concentrations of SHP647 versus time was reported.	Baseline, Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72 and 156
Number of Participants With Positive Anti-drug (SHP647) Antibodies (ADA)	The anti-drug antibodies (ADA) positive was defined as ADA log base 2 titer greater than or equal to (>=) 4.64. The number of participants with positive ADA was reported.	Baseline, Week 8, 16, 24, 40, 48, 64 and 156
Number of Participants With Positive Neutralizing Antibodies (NAb)	The positive Neutralizing Antibodies (NAb) was defined as NAb titer greater than or equal to (>=) 0.903. The number of participants with NAb was reported. Here "inconclusive" refers to participants who were neither reported as positive nor negative for NAb and anti-drug antibodies (ADA) positive was defined as ADA log base 2 titer greater than or equal to (>=) 4.64.	Baseline, Week 8, 16, 24, 40, 48, 64 and 156

Collaborators and Investigators

• Sponsor: Shire
• Investigators: Study Director: Shire Director, Takeda

Study record dates

Study Major Dates

• Study Start (Actual): March 18, 2013
• Primary Completion (Actual): December 13, 2017
• Study Completion (Actual): December 13, 2017

Study Registration Dates

• First Submitted: January 8, 2013
• First Submitted That Met QC Criteria: January 16, 2013
• First Posted (Estimate): January 18, 2013

Study Record Updates

• Last Update Posted (Actual): June 3, 2021
• Last Update Submitted That Met QC Criteria: May 11, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: Anti-TNF Refractory; Active Ulcerative Colitis; Immunosuppressant Refractory
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Gastrointestinal Diseases; Gastroenteritis; Colonic Diseases; Intestinal Diseases; Inflammatory Bowel Diseases; Ulcer; Colitis; Colitis, Ulcerative
• Other Study ID Numbers: A7281010; 2012-002031-28 (EudraCT Number); TURANDOT II (Other Identifier: Alias Study Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
• IPD Sharing Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No