Clinical trial NCT01276509: Study To Test Whether PF-00547659 Is Safe And Improves Disease Symptoms In Patients With Crohn's Disease
Official title: A Double-blind, Randomized, Placebo-controlled, Dose-ranging Study To Evaluate The Efficacy And Safety Of Pf-00547659 In Subjects With Crohn's Disease (Opera)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Crohn's Disease
Keywords: Crohn's disease Safety Efficacy Pharmacokinetics Pharmacodynamics Crohn's Disease Activity Index (CDAI)
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2011-01-13
Enrollment: 265
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Adults with Crohn's disease that is clinically active despite conventional treatment will be eligible for this study. Patients may receive one of three doses of PF-00547659 (experimental drug) or placebo (inactive drug). Disease activity will be measured every two weeks.


Eligibility criteria: Inclusion Criteria:

* Subjects must have failed or are intolerant to anti-TNFs and/or immunosuppressants (AZA, 6-MP, and/or MTX).
* hsCRP greater than 3mg/L
* Ulcerations demonstrated by colonoscopy performed during screening or 8 weeks prior to screening

Exclusion Criteria:

* Pregnant or breast feeding
* Short bowel syndrome due to multiple small bowel resections
* Presence of a stoma

Primary outcomes:
measure: Percentage of Participants With Crohn's Disease Activity Index (CDAI) 70 Response Rate
timeFrame: Week 8 and week 12
Secondary outcomes:
measure: Safety and Tolerability of PF-00547659 Dose Levels Versus Placebo
timeFrame: Week 0-12
measure: Number of Adverse Events (AEs) - PF-00547659 Dose Levels Versus Placebo
timeFrame: Week 0-12
measure: Percentage of Participants With a Crohn's Disease Activity Index (CDAI) Remission
timeFrame: Weeks 8 and week 12
measure: Crohn's Disease Activity Index (CDAI)-70 Response Rates Over Time
timeFrame: Week 2, 4, 6, 8, 10 and 12
measure: Crohn's Disease Activity Index (CDAI) -100 Response Rates Over Timer
timeFrame: Week 2, 4, 6, 8, 10 and 12
measure: Immunogenicity Assessment of Anti-drug Antibodies (ADAs)
timeFrame: Day 1, Week 4, Week 8, Week 12, Week 20, Week 28, Week 36
measure: The Pharmacokinetics (PK) of Total PF-00547659 - Area Under the Concentration Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf)
timeFrame: Day 1, 14, 28, 42, 56, 70, 84, 112, 140, 168, 196, 224 and 252
measure: The Pharmacokinetics (PK) of Total PF-00547659 - Area Under the Concentration Time Profile From Time Zero to Time Tau (AUCtau)
timeFrame: Day 1, 14, and 28
measure: The Pharmacokinetics (PK) of Total PF-00547659 - Maximum Observed Concentration (Cmax)
timeFrame: Day 1, 14, 28, 42, 56, 70, 84, 112, 140, 168, 196, 224 and 252
measure: The Pharmacokinetics (PK) of Total PF-00547659 - Time for Cmax (Tmax)
timeFrame: Day 1, 14, 28, 42, 56, 70, 84, 112, 140, 168, 196, 224 and 252
measure: The Pharmacokinetics (PK) of Total PF-00547659 - Terminal Half Life (Thalf)
timeFrame: Day 1, 14, 28, 42, 56, 70, 84, 112, 140, 168, 196, 224 and 252
measure: The Pharmacokinetics (PK) of Total PF-00547659 - Apparent Clearance (CL/F)
timeFrame: Day 1, 14, 28, 42, 56, 70, 84, 112, 140, 168, 196, 224 and 252
Other outcomes:
Locations:
city: Jonesboro
country: United States
facility: Clopton Clinic
state: Arkansas
city: Jonesboro
country: United States
facility: Gastroenterology Specialists of Arkansas
state: Arkansas
city: Little Rock
country: United States
facility: Little Rock Diagnostic Clinic, P.A.
state: Arkansas
city: La Jolla
country: United States
facility: UCSD Medical Center-Thornton Hospital
state: California
city: Orange
country: United States
facility: Community Clinical Trials
state: California
city: Orange
country: United States
facility: Gastro Diagnostics
state: California
city: Redlands
country: United States
facility: Inland Gastroenterology Medical Associates, Inc.
state: California
city: Whittier
country: United States
facility: BioMark Research Inc.
state: California
city: Lafayette
country: United States
facility: Clinical Research of the Rockies
state: Colorado
city: Thornton
country: United States
facility: Rocky Mountain Gastroenterology Associates
state: Colorado
city: Bristol
country: United States
facility: Connecticut Clinical Research Foundation
state: Connecticut
city: Gainesville
country: United States
facility: Shands Endoscopy Center
state: Florida
city: Gainesville
country: United States
facility: Shands Hospital at the University of Florida
state: Florida
city: Gainesville
country: United States
facility: Shands Medical Plaza
state: Florida
city: Jacksonville
country: United States
facility: Mayo Clinic Jacksonville
state: Florida
city: Largo
country: United States
facility: Florida Center for Gastroenterology
state: Florida
city: Miami
country: United States
facility: Sylvester Comprehensive Cancer Center
state: Florida
city: Miami
country: United States
facility: University of Miami Hospital and Clinic
state: Florida
city: Miami
country: United States
facility: University of Miami Hospital
state: Florida
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Orlando
country: United States
facility: Cirtus Ambulartory Surgery Center
state: Florida
city: Orlando
country: United States
facility: Internal Medicine Specialists
state: Florida
city: Clive
country: United States
facility: Heartland Medical Research (Administrative Only)
state: Iowa
city: Clive
country: United States
facility: Iowa Digestive Disease Center
state: Iowa
city: Clive
country: United States
facility: Iowa Endoscopy Center (Colonoscopy Only)
state: Iowa
city: Chevy Chase
country: United States
facility: Metropolitan Gastroenterology Group, PC - Chevy Chase Clinical Research
state: Maryland
city: Worcester
country: United States
facility: UMass Memorial Medical Center
state: Massachusetts
city: Worcester
country: United States
facility: University of Massachusetts Worcester
state: Massachusetts
city: Troy
country: United States
facility: Center for Digestive Health
state: Michigan
city: Troy
country: United States
facility: Surgical Centers of Michigan
state: Michigan
city: Minneapolis
country: United States
facility: Minneapolis Heart Institute, West Health Campus
state: Minnesota
city: Minneapolis
country: United States
facility: Noran Neurology Clinic
state: Minnesota
city: Plymouth
country: United States
facility: Consulting Radiology (Xray testing only)
state: Minnesota
city: Plymouth
country: United States
facility: Minnesota Gastroenterology, P.A.
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Columbia
country: United States
facility: Surgery Center of Columbia
state: Missouri
city: Mexico
country: United States
facility: Audrain Medical Center
state: Missouri
city: Mexico
country: United States
facility: Center for Digestive and Liver Diseases, Inc.
state: Missouri
city: Saint Louis
country: United States
facility: Barnes-Jewish Hospital - Investigational Drug Services
state: Missouri
city: Saint Louis
country: United States
facility: Center for Advanced Medicine
state: Missouri
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Albany
country: United States
facility: Albany Medical College
state: New York
city: Brooklyn
country: United States
facility: Life Medi-Research And Management
state: New York
city: Flushing
country: United States
facility: New York Hospital Queens
state: New York
city: Great Neck
country: United States
facility: Long Island Clinical Research Associates, LLP
state: New York
city: Great Neck
country: United States
facility: Nassau Gastroenterology Associates Office Based Surgery
state: New York
city: Great Neck
country: United States
facility: Nassau Gastroenterology Associates, P.C.
state: New York
city: Great Neck
country: United States
facility: North Shore Primary Care, P.C.
state: New York
city: New York
country: United States
facility: Beth Israel Medical Center - Phillip Ambulatory Care Center
state: New York
city: New York
country: United States
facility: East side Endoscopy, LLC (for colonscopy testing only)
state: New York
city: New York
country: United States
facility: Lenox Hill Endoscopy Center
state: New York
city: Poughkeepsie
country: United States
facility: Premier Medical Group of the Hudson Valley
state: New York
city: Chapel Hill
country: United States
facility: CTRC Hospital - UNC Memorial Hospital
state: North Carolina
city: Chapel Hill
country: United States
facility: North Carolina Memorial Hospital Endoscopy Center
state: North Carolina
city: Chapel Hill
country: United States
facility: UNC Hospitals Department of Pharmacy
state: North Carolina
city: Chapel Hill
country: United States
facility: UNC Hospitals Endoscopy
state: North Carolina
city: Hillsborough
country: United States
facility: Hillsborough Campus
state: North Carolina
city: Philadelphia
country: United States
facility: Thomas Jefferson University Hospital
state: Pennsylvania
city: East Providence
country: United States
facility: The Offices of Dr. Vincent Armenio, M.D.
state: Rhode Island
city: East Providence
country: United States
facility: Pharma Resource
state: Rhode Island
city: Providence
country: United States
facility: Bayside Endoscopy Center
state: Rhode Island
city: Nashville
country: United States
facility: Nashville Medical Research Institute
state: Tennessee
city: Pasadena
country: United States
facility: Pasadena Gastroenterology Associates, P.A. dba Digestive Health Center
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah HSC
state: Utah
city: Charlottesville
country: United States
facility: Charlottesville Gastroenterology Associates
state: Virginia
city: Charlottesville
country: United States
facility: Charlottesville Medical Research
state: Virginia
city: Seattle
country: United States
facility: University of Washington Medical Center
state: Washington
city: Wauwatosa
country: United States
facility: Allegiance Research Specialists
state: Wisconsin
city: Wauwatosa
country: United States
facility: GI Associates
state: Wisconsin
city: Wien
country: Austria
facility: AKH Wien Universitaetsklinik fuer Innere Medizin III
city: Leuven
country: Belgium
facility: UZ Gasthuisberg
city: Liege
country: Belgium
facility: Centre Hospitalier Universitaire de Liege
city: Liege
country: Belgium
facility: Centre Hospitalier Universitaire de Liège - Labo Biologie Clinique
city: Mouscron
country: Belgium
facility: Centre Hospitalier de Mouscron
city: Sofia
country: Bulgaria
facility: 4-MHAT
city: Sofia
country: Bulgaria
facility: MBAL Sofiamed OOD,Otdelenie po gastroenterologia
city: Vancouver
country: Canada
facility: Vancouver Coastal Health - Vancouver General Hospital
state: British Columbia
city: Vancouver
country: Canada
facility: Vancouver Coastal Health - Vancouver Hospital
state: British Columbia
city: Oshawa
country: Canada
facility: Oshawa Clinic
state: Ontario
city: Vaughan
country: Canada
facility: Toronto Digestive Disease Associates Inc.
state: Ontario
city: Amiens Cedex 01
country: France
facility: CHU Amiens Hopital Nord Service d'Hepato-Gastroenterologie
city: Bordeaux cedex
country: France
facility: Hopital Saint-Andre
city: Clichy Cedex
country: France
facility: Hopital Beaujon- Essais cliniques
city: NICE Cedex 3
country: France
facility: Hopital de l'Archet 2 - CHU de Nice
city: Paris
country: France
facility: Hopital Cochin-Essais Cliniques
city: Rouen Cedex 1
country: France
facility: Hopital Charles Nicolle
city: St Priest En Jarez
country: France
facility: Hopital Nord
city: Toulouse cedex 09
country: France
facility: Hopital Rangueil
city: Berlin
country: Germany
facility: Charite - Campus Berlin Mitte Medizinische Klinik
city: Halle
country: Germany
facility: Krankenhaus Martha-Maria Halle-Doelau gGmbH
city: Kiel
country: Germany
facility: Universitaetsklinikum Schleswig-Holstein
city: Luebeck
country: Germany
facility: Universitaetsfrauenklinikum Schleswig-Holstein Medizinische Klinik I, Gastroenterologie/Hepatologie
city: Minden
country: Germany
facility: Gastroenterologische Gemeinschaftspraxis Minden
city: Regensburg
country: Germany
facility: Universitaetsklinikum Regensburg
city: Stuttgart
country: Germany
facility: Robert-Bosch-Krankenhaus
city: Ulm
country: Germany
facility: Universitaetklinikum Ulm
city: Hirosaki
country: Japan
facility: National Hospital Organization Hirosaki National Hospital
state: Aomori
city: Takasaki
country: Japan
facility: National Hospital Organization Takasaki General Medical Center
state: Gunma
city: Minato-ku
country: Japan
facility: Jikei University Hospital
state: Tokyo
city: Shinjuku-ku
country: Japan
facility: Keio University Hospital
state: Tokyo
city: Aichi
country: Japan
facility: Aichi Medical University Hospital
city: Chiba
country: Japan
facility: Chiba University Hospital
city: Kanagawa
country: Japan
facility: Yokohama City University Medical Center
city: Busan
country: Korea, Republic of
facility: Pusan National University Hospital
city: Daegu
country: Korea, Republic of
facility: Yeungnam University Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Kangbuk Samsung Hospital
city: Seoul
country: Korea, Republic of
facility: Yonsei University College of Medicine, Severance Hospital
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Groningen
country: Netherlands
facility: University Medical Center Groningen (UMCG)
state: GR
city: Amsterdam
country: Netherlands
facility: Academic Medical Center
state: NH
city: Maastricht
country: Netherlands
facility: Maastricht University Medical Center
city: Gjettum
country: Norway
facility: Asker And Baerum Hospital
city: Oslo
country: Norway
facility: Oslo Universitetssykehus
city: Oslo
country: Norway
facility: Lovisenberg Diakonale Sykehus
city: Bydgoszcz
country: Poland
facility: Szpital Uniwersytecki nr 2 im dr. Jana Bizieta w Bydgoszczy Centrum Endoskopii Zabiegowej
city: Lodz
country: Poland
facility: Centrum Medyczne-Szpital Swietej Rodziny Sp. z o.o.
city: Warszawa
country: Poland
facility: Centralny Szpital Kliniczny Ministerstwa Spraw Wewnetrznych w Warszawie
city: Wroclaw
country: Poland
facility: Lexmedica
city: Belgrade
country: Serbia
facility: Military Medical Academy
city: Belgrade
country: Serbia
facility: Clinical Hospital Centre Bezanijska Kosa
city: Nis
country: Serbia
facility: Clinical Center Nis Clinic for Gastroenterology and Hepatology
city: Zemun
country: Serbia
facility: Clinical Hospital Center Zemun
city: Bratislava
country: Slovakia
facility: Gastroentero-Hepatologicke centrum THALION, LAMA MEDICAL CARE s.r.o.
city: Bratislava
country: Slovakia
facility: Medak s.r.o.
city: Nitra
country: Slovakia
facility: Gastroenterologicke a hepatologicke centrum Nitra, KM Management spol. s r.o.
city: Nove Mesto Nad Vahom
country: Slovakia
facility: Synergy group, a.s.
city: Johannesburg
country: South Africa
facility: Wits Clinical Research
state: Gauteng
city: Durban
country: South Africa
facility: Parklands Medical Centre
state: Kwa-zulu - Natal
city: Cape Town
country: South Africa
facility: Kingsbury Hospital
state: Western CAPE
city: Majadahonda
country: Spain
facility: Hospital Puerta de Hierro Majadahonda
state: Madrid
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: Barcelona
country: Spain
facility: Hospital Universitari Bellvitge
city: Madrid
country: Spain
facility: Hospital Universitario de La Princesa
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Maranon
city: Sabadell
country: Spain
facility: Corporacio Sanitaria Parc Tauli de Sabadell
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References:
citation: Saruta M, Park DI, Kim YH, Yang SK, Jang BI, Cheon JH, Im JP, Kanai T, Katsuno T, Ishiguro Y, Nagaoka M, Isogawa N, Li Y, Banerjee A, Ahmad A, Hassan-Zahraee M, Clare R, Gorelick KJ, Cataldi F, Watanabe M, Hibi T. Anti-MAdCAM-1 antibody (PF-00547659) for active refractory Crohn's disease in Japanese and Korean patients: the OPERA study. Intest Res. 2020 Jan;18(1):45-55. doi: 10.5217/ir.2019.00039. Epub 2020 Jan 30.
citation: Sandborn WJ, Lee SD, Tarabar D, Louis E, Klopocka M, Klaus J, Reinisch W, Hebuterne X, Park DI, Schreiber S, Nayak S, Ahmad A, Banerjee A, Brown LS, Cataldi F, Gorelick KJ, Cheng JB, Hassan-Zahraee M, Clare R, D'Haens GR. Phase II evaluation of anti-MAdCAM antibody PF-00547659 in the treatment of Crohn's disease: report of the OPERA study. Gut. 2018 Oct;67(10):1824-1835. doi: 10.1136/gutjnl-2016-313457. Epub 2017 Oct 5.
citation: Hassan-Zahraee M, Banerjee A, Cheng JB, Zhang W, Ahmad A, Page K, von Schack D, Zhang B, Martin SW, Nayak S, Reddy P, Xi L, Neubert H, Fernandez Ocana M, Gorelick K, Clare R, Vincent M, Cataldi F, Hung K. Anti-MAdCAM Antibody Increases ss7+ T Cells and CCR9 Gene Expression in the Peripheral Blood of Patients With Crohn's Disease. J Crohns Colitis. 2018 Jan 5;12(1):77-86. doi: 10.1093/ecco-jcc/jjx121.