Clinical trial NCT01287897: A Study To Assess The Efficacy And Safety Of PF-04236921 In Subjects With Crohn's Disease Who Failed Anti-TNF Therapy
Official title: A Double-blind, Randomized, Placebo-controlled, Dose-ranging Study To Evaluate The Efficacy And Safety Of Pf-04236921 In Subjects With Crohn's Disease Who Are Anti-tnf Inadequate Responders (Andante)
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: Pfizer
Sponsor class: INDUSTRY
First posted: 2011-02-02
Enrollment: 250
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: This is a proof of concept study to determine the efficacy and safety of a monoclonal antibody with three doses versus placebo. Subjects will be randomized to a treatment and the dose will be delivered subcutaneously twice, 4 weeks apart. All subjects will have moderate to severe refractory Crohn's Disease.


Eligibility criteria: Inclusion Criteria:

* Subjects must have failed or are intolerant to anti TNFs
* hsCRP greater or equal to 5.0 mg/L
* Ulcerations demonstrated by colonoscopy as defined by SES CD assessment performed within 8 weeks of study entry (screening) and able to retrospectively complete the SES-CD or colonoscopy performed during screening

Exclusion Criteria:

* Pregnant or breastfeeding women
* Crohn's Disease with active fistulae or abscess
* History of diverticulitis or symptomatic diverticulosis
* Abnormality in hematology or chemistry profiles at screening

Primary outcomes:
measure: The Crohn's Disease Activity Index (CDAI)-70 Response Rate at Week 8 in Participants Who Received Placebo, PF-04236921 10 mg and PF-04236921 50 mg
timeFrame: Baseline and Week 8
measure: The CDAI-70 Response Rate at Week 8 in Participants Who Received Placebo and PF-04236921 200 mg
timeFrame: Baseline and Week 8
measure: The CDAI-70 Response Rate at Week 12 in Participants Who Received Placebo, PF-04236921 10 mg and PF-04236921 50 mg
timeFrame: Baseline and Week 12
measure: The CDAI-70 Response Rate at Week 12 in Participants Who Received Placebo and PF-04236921 200 mg
timeFrame: Baseline and Week 12
Secondary outcomes:
measure: The CDAI-70 Response Rate Over Time in Participants Who Received Placebo, PF-04236921 10 mg and PF-04236921 50 mg
timeFrame: Baseline and Weeks 2, 4, 6, and 10
measure: The CDAI-70 Response Rate Over Time in Participants Who Received Placebo and PF-04236921 200 mg
timeFrame: Baseline and Weeks 2, 4, 6, and 10
measure: The CDAI Remission Rate Over Time in Participants Who Received Placebo, PF-04236921 10 mg and PF-04236921 50 mg
timeFrame: Baseline and Weeks 2, 4, 6, 8, 10, and 12
measure: The CDAI Remission Rate Over Time in Participants Who Received Placebo and PF-04236921 200 mg
timeFrame: Baseline and Weeks 2, 4, 6, 8, 10, and 12
measure: The CDAI-100 Response Rate Over Time in Participants Who Received Placebo, PF-04236921 10 mg and PF-04236921 50 mg
timeFrame: Baseline and Weeks 2, 4, 6, 8, 10, and 12
measure: The CDAI-100 Response Rate Over Time in Participants Who Received Placebo and PF-04236921 200 mg
timeFrame: Baseline and Weeks 2, 4, 6, 8, 10, and 12
measure: Change From Baseline in CDAI Score Over Time in Participants Who Received Placebo, PF-04236921 10 mg and PF-04236921 50 mg
timeFrame: Baseline and Weeks 2, 4, 6, 8, 10, and 12
measure: Change From Baseline in CDAI Score Over Time in Participants Who Received Placebo and PF-04236921 200 mg
timeFrame: Baseline and Weeks 2, 4, 6, 8, 10, and 12
measure: Percentages of Participants With Confirmed Positive Anti-drug Antibodies (ADAs)
timeFrame: At baseline (Day 1) and at Weeks 4, 8, 12, 16, 24, 32 and 40
measure: Percentages of Participants With Confirmed Positive Neutralizing Antibodies (NAbs)
timeFrame: At baseline (Day 1) and at Weeks 4, 8, 12, 16, 24, 32 and 40
measure: Serum PF-04236921 Concentration Over Time
timeFrame: Day 1 (predose), and at Weeks 2, 4 (Day 28, predose), 8, 10, 12, 16, 20, 24, 28, 32, 36, and 40
measure: Number of Participants Who Withdrew From the Study Due to Treatment-emergent Adverse Events (AEs)
timeFrame: Induction period: from Week 0 (Day 1) through Week 12; follow-up period: from Week 12 (or discontinuation from the induction period) through last subject visit (up to 28 weeks after completion of or discontinuation from the 12-week induction period)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: UAB Hospital
state: Alabama
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Scottsdale
country: United States
facility: Simon Medical Imaging
state: Arizona
city: Scottsdale
country: United States
facility: Digestive Health Research Unit
state: Arizona
city: Tucson
country: United States
facility: Adobe Clinical Research, Llc
state: Arizona
city: Tucson
country: United States
facility: Radiology Ltd
state: Arizona
city: San Francisco
country: United States
facility: UCSF Endoscopy Unit at Mount Zion
state: California
city: San Francisco
country: United States
facility: University of California - San Francisco
state: California
city: San Francisco
country: United States
facility: University of California San Francisco at Mount Zion
state: California
city: Denver
country: United States
facility: Rocky Mountain Clinical Research, LLC
state: Colorado
city: Lakewood
country: United States
facility: Rocky Mountain Gastroenterology Associates
state: Colorado
city: Lakewood
country: United States
facility: Rocky Mountain Gastroenterology
state: Colorado
city: Littleton
country: United States
facility: Arapahoe Gastroenterology, PC
state: Colorado
city: Guilford
country: United States
facility: Endoscopy Center of Connecticut, LLC
state: Connecticut
city: Hamden
country: United States
facility: Endoscopy Center of Connecticut, LLC
state: Connecticut
city: Hamden
country: United States
facility: Gastroenterology Center of Connecticut, PC
state: Connecticut
city: Hamden
country: United States
facility: Medical Research Center of Connecticut, LLC
state: Connecticut
city: Clearwater
country: United States
facility: Clinical Research of West Florida, Inc.
state: Florida
city: Crystal River
country: United States
facility: Gastroenterology Associates
state: Florida
city: Inverness
country: United States
facility: Nature Coast Clinical Research
state: Florida
city: Inverness
country: United States
facility: Suncoast Endoscopy Center
state: Florida
city: New Port Richey
country: United States
facility: Advanced Research Institute, Inc.
state: Florida
city: Sanford
country: United States
facility: International Clinical Research - US, LLC
state: Florida
city: Decatur
country: United States
facility: Atlanta Center for Gastroenterology, P.C.
state: Georgia
city: Decatur
country: United States
facility: Atlanta Endoscopy Center
state: Georgia
city: Decatur
country: United States
facility: Decatur Health Imaging
state: Georgia
city: Marietta
country: United States
facility: Gastrointestinal Specialists of Georgia, PC
state: Georgia
city: Marietta
country: United States
facility: GI Diagnostics
state: Georgia
city: Arlington Heights
country: United States
facility: Illinois Gastroenterology Group, LLC
state: Illinois
city: Chicago
country: United States
facility: The University of Chicago Medical Center (Ucmc)
state: Illinois
city: Chicago
country: United States
facility: The University of Chicago Medical Center
state: Illinois
city: Chicago
country: United States
facility: The University of Chicago Medical
state: Illinois
city: Chicago
country: United States
facility: The University Of Chicago
state: Illinois
city: Evanston
country: United States
facility: NorthShore University Health System
state: Illinois
city: Glenview
country: United States
facility: Glenbrook Hospital Outpatient Pharmacy
state: Illinois
city: Glenview
country: United States
facility: Glenbrook Hospital
state: Illinois
city: Anderson
country: United States
facility: Central Indiana Gastroenterology Group
state: Indiana
city: Anderson
country: United States
facility: Saint John's Research Institute
state: Indiana
city: Lexington
country: United States
facility: University of Kentucky
state: Kentucky
city: Louisville
country: United States
facility: University Of Louisville Healthcare Outpatient Center
state: Kentucky
city: Louisville
country: United States
facility: University of Louisville Research Foundation
state: Kentucky
city: Louisville
country: United States
facility: University Of Louisville
state: Kentucky
city: Annapolis
country: United States
facility: Digestive Disorders Associates
state: Maryland
city: Annapolis
country: United States
facility: Disgestive Disorders Associates
state: Maryland
city: Annapolis
country: United States
facility: Investigative Clinical Research
state: Maryland
city: Annapolis
country: United States
facility: Maryland Diagnostics & Therapeutic Endo Center
state: Maryland
city: Brockton
country: United States
facility: Commonwealth Clinical Studies
state: Massachusetts
city: Fall River
country: United States
facility: Prima CARE, PC
state: Massachusetts
city: Ann Arbor
country: United States
facility: St. Joseph Mercy Hospital
state: Michigan
city: Grand Rapids
country: United States
facility: East Valley Endoscopy
state: Michigan
city: Wyoming
country: United States
facility: Gastroenterology Associates of Western Michigan
state: Michigan
city: Wyoming
country: United States
facility: Metro Health Hospital Endoscopy Unit
state: Michigan
city: Wyoming
country: United States
facility: Metro Health Hospital
state: Michigan
city: Ypsilanti
country: United States
facility: Huron Gastroenterology Associates
state: Michigan
city: Ypsilanti
country: United States
facility: St. Joseph Mercy Hospital
state: Michigan
city: Plymouth
country: United States
facility: Minnesota Gastroenterology, PA
state: Minnesota
city: New York
country: United States
facility: Weill Cornell Medical College of Cornell University-Greenberg
state: New York
city: New York
country: United States
facility: Weill Cornell Medical College of Cornell University
state: New York
city: New York
country: United States
facility: Present Chapman, Steinlauf and Marion
state: New York
city: New York
country: United States
facility: Mount Sinai School of Medicine
state: New York
city: New York
country: United States
facility: New York Presbyterian Hospital - Weill Cornell Medical College Investigational Pharmacy
state: New York
city: New York
country: United States
facility: New York Presbyterian Hospital
state: New York
city: New York
country: United States
facility: Weill Cornell Imaging at New York Presbyterian Hospital
state: New York
city: New York
country: United States
facility: Arthur asher Kornbluth, MD PC
state: New York
city: Winston-Salem
country: United States
facility: PMG Research of Winston-Salem
state: North Carolina
city: Oklahoma City
country: United States
facility: Oklahoma Foundation for Digestive Research
state: Oklahoma
city: Oklahoma City
country: United States
facility: Pharmacy: Wheeler and Stuckey, Inc.
state: Oklahoma
city: Oklahoma City
country: United States
facility: Colonoscopy and X-rays: OU Physicians Building
state: Oklahoma
city: Tulsa
country: United States
facility: Hillcrest Medical Center Endoscopy
state: Oklahoma
city: Tulsa
country: United States
facility: Hillcrest Medical Center
state: Oklahoma
city: Tulsa
country: United States
facility: Options Health Research, LLC
state: Oklahoma
city: Tulsa
country: United States
facility: Utica Park Clinic X-Ray
state: Oklahoma
city: Tulsa
country: United States
facility: Advanced Imaging
state: Oklahoma
city: Pittsburgh
country: United States
facility: Pittsburgh Gastroenterology Associates
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Research Protocol Management Specialists
state: Pennsylvania
city: East Providence
country: United States
facility: Pharma Resource
state: Rhode Island
city: Warwick
country: United States
facility: Omega Medical Research
state: Rhode Island
city: Germantown
country: United States
facility: Gastro One
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Austin
country: United States
facility: Professional Quality Research, Inc.
state: Texas
city: Houston
country: United States
facility: Diagnostic Clinic of Houston, PA
state: Texas
city: Houston
country: United States
facility: Houston Hospital for Specialized Surgery (Endoscopy Only)
state: Texas
city: Houston
country: United States
facility: Baylor Clinic (Drug Storage)
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine - Baylor Medical Center
state: Texas
city: Houston
country: United States
facility: Ertan Digestive Disease Center
state: Texas
city: Houston
country: United States
facility: Memorial Hermann Hospital
state: Texas
city: Houston
country: United States
facility: The University of Texas Health Science Center at Houston
state: Texas
city: Houston
country: United States
facility: The University of Texas Medical School at Houston
state: Texas
city: Houston
country: United States
facility: Physicians Endoscopy Center (Colonoscopy)
state: Texas
city: Southlake
country: United States
facility: Texas Digestive Disease Consultants
state: Texas
city: Sugar Land
country: United States
facility: One Step Diagnostic (X-Ray)
state: Texas
city: Sugar Land
country: United States
facility: Pioneer Research Solutions, Inc. (Admin. Office)
state: Texas
city: SugarLand
country: United States
facility: Pioneer Research Solutions, Inc.
state: Texas
city: Tyler
country: United States
facility: Digestive Health Specialists of Tyler
state: Texas
city: Salt Lake City
country: United States
facility: University Of Utah HSC
state: Utah
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
city: Richmond
country: United States
facility: VCU Medical Investigational Drug Service (IDS)
state: Virginia
city: Concord
country: Australia
facility: Concord Repatriation General Hospital
state: New South Wales
city: Kingswood
country: Australia
facility: Nepean Public Hospital
state: New South Wales
city: Herston, Brisbane
country: Australia
facility: Royal Brisbane and Women's Hospital
state: Queensland
city: South Brisbane
country: Australia
facility: Mater Health Services
state: Queensland
city: Box Hill
country: Australia
facility: Eastern Health, Box Hill Hospital
state: Victoria
city: Clayton
country: Australia
facility: Monash Medical Centre
state: Victoria
city: Parkville
country: Australia
facility: The Royal Melbourne Hospital
state: Victoria
city: Fitzroy
country: Australia
facility: St. Vincent's Hospital Melbourne
city: Leuven
country: Belgium
facility: University Hospital Leuven
state: Vlaams Brabant
city: Bruxelles
country: Belgium
facility: CHU Saint-Pierre
city: Leuven
country: Belgium
facility: UZ Leuven Pharmacy
city: Roeselare
country: Belgium
facility: An Spiessens H.-Hartziekenhuis Roeselare-Menen vzw
city: Goiania
country: Brazil
facility: Clinica do Coracao Samaritano
state: GO
city: Goiania
country: Brazil
facility: Instituto Goiano de Gastroenterologia e Endoscopia Digestiva Ltda.
state: GO
city: Goiania
country: Brazil
facility: Center X Diagnosticos
state: GO
city: Rio de Janeiro
country: Brazil
facility: Hospital Universitário Fraga Filho da UFRJ
state: RJ
city: Porto Alegre
country: Brazil
facility: Hospital Sao Lucas da PUCRS
state: RS
city: Santo Andre
country: Brazil
facility: Faculdade de Medicina do ABC
state: SP
city: São Paulo
country: Brazil
facility: Hospital Israelita Albert Einstein
state: SP
city: Curitiba
country: Brazil
facility: Hospital Nossa Senhora das Gracas
city: Calgary
country: Canada
facility: Heritage Medical Research Clinic - University of Calgary
state: Alberta
city: London
country: Canada
facility: London Health Science Centre - University Hospital
state: Ontario
city: Toronto
country: Canada
facility: Mount Sinai Hospital
state: Ontario
city: Montreal
country: Canada
facility: McGill University Health Centre - Royal Victoria Hospital
state: Quebec
city: Hradec Kralove
country: Czech Republic
facility: Hepato-Gastroenterologie HK, s.r.o.
city: Hradec Kralove
country: Czech Republic
facility: Medial Pharma s.r.o.,
city: Olomouc
country: Czech Republic
facility: Fakultni nemocnice Olomouc
city: Prague
country: Czech Republic
facility: Klinicke centrum ISCARE I.V.F. - gastroenterologie
city: Praha 10
country: Czech Republic
facility: Fakultni nemocnice Kralovske Vinohrady
city: Praha 4
country: Czech Republic
facility: Institut klinicke a experimentalni mediciny
city: Praha 7
country: Czech Republic
facility: IBD Clinical and Research centre
city: Usti nad Labem
country: Czech Republic
facility: Krajska zdravotni, a.s.
city: Aalborg
country: Denmark
facility: Aalborg Sygehus
city: Aarhus C
country: Denmark
facility: Aarhus Universitetshospital, Aarhus Sygehus Aarhus University Hospital
city: Herlev
country: Denmark
facility: Gastroenheden
city: Hilleroed
country: Denmark
facility: Kirurgisk Afdeling 0143
city: Hvidovre
country: Denmark
facility: Hvidovre Hospital
city: Koebenhavn NV
country: Denmark
facility: Afdeling I, Gastroenterologisk Sektion
city: Koebenhavn
country: Denmark
facility: Rigshospitalet
city: Koege
country: Denmark
facility: Medicinsk Afdeling, Gastroenterologisk Sektion
city: Lille Cedex
country: France
facility: Hopital Huriez, CHRU de Lille
city: Paris Cedex 12
country: France
facility: Hopital Saint-Antoine - Service De Gastroenterologie
city: Vandoeuvre Les Nancy
country: France
facility: Hopital de Brabois
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
state: Niedersachsen
city: Berlin
country: Germany
facility: "Charite - Campus Benjamin Franklin
city: Hamburg
country: Germany
facility: Praxis Dr. Howaldt
city: Kiel
country: Germany
facility: Universitaetsklinikum Schleswig-Holstein
city: Minden
country: Germany
facility: Gastroenterologische Gemeinschaftspraxis Minden
city: Regensburg
country: Germany
facility: Universitaetsklinik Regensburg
city: Athens
country: Greece
facility: University General Hospital "Attikon"
city: Kolonaki Athens
country: Greece
facility: General Hospital of Athens "Evangelismos",1st Gastroenterology Department
city: Budapest
country: Hungary
facility: Semmelweis Egyetem II. Sz. Belgyogyaszati Klinika
city: Budapest
country: Hungary
facility: Szent Janos Korhaz es Eszak-budai Egyesitett Korhazak./I. Belgyogyaszati-Gasztroenterologiai
city: Budapest
country: Hungary
facility: Pannonia Maganorvosi Centrum Kft.
city: Debrecen
country: Hungary
facility: Debreceni Egyetem Orvos- es Egeszsegtudomanyi Centrum
city: Szeged
country: Hungary
facility: Szegedi Tudomanyegyetem Altalanos Orvostudomanyi Kar / I. sz. Belgyogyaszati Klinika
city: Szekszard
country: Hungary
facility: Clinfan Kft.
city: Dublin 4
country: Ireland
facility: St. Vincents University Hospital
city: Dublin
country: Ireland
facility: Beaumont Hospital
city: Dublin
country: Ireland
facility: National Virus Reference Laboratory
city: Dublin
country: Ireland
facility: Pathology, Haematology and Biochemistry Laboratories, St Vincent's Healthcare Group
city: Dublin
country: Ireland
facility: Mater Misericordiae Hospital, Department of Clinical Chemistry and Clinical Haematology
city: Galway
country: Ireland
facility: University Hospital Galway
city: Tel Hashomer
country: Israel
facility: The Institute Of Gastroenterology & Liver Diseases
state: Ramat Gan
city: Haifa
country: Israel
facility: Institute of Gastroenterology
city: Holon
country: Israel
facility: The E. Wolfson Medical Center
city: Jerusalem
country: Israel
facility: Shaare Zedek Medical Center
city: Jerusalem
country: Israel
facility: Hadassah Medical Center
city: Kfar Saba
country: Israel
facility: Dept of Gastroenterology & Hepatology
city: Petach Tikva
country: Israel
facility: Rabin Medical Center, Beilinson Hospital
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center
city: Zerifin
country: Israel
facility: Assaf Harofeh Medical Center
city: San Giovanni Rotondo Fg
country: Italy
facility: Casa Sollievo della Sofferenza/Div.Gastroenterologia Endoscopia Digestiva
state: Foggia
city: Rozzano
country: Italy
facility: Istituto Clinico Humanitas IRCCS
state: Milano
city: Rome
country: Italy
facility: A. Gemelli University Hospital-Department of Medical Sciences - Division of Internal Medicine and
state: Province of Rome
city: Bologna
country: Italy
facility: Azienda Ospedaliero Universitaria di Bologna Policlinico Sant'Orsola Malpighi
city: Padova
country: Italy
facility: Azienda Ospedaliera - Universita di Padova
city: Roma
country: Italy
facility: Università Campus Biomedico
city: Roma
country: Italy
facility: Policlinico Tor Vergata
city: Roma
country: Italy
facility: Azienda Ospedaliera San Camillo Forlanini
city: Milford
country: New Zealand
facility: Shakespeare Specialist Group
state: Auckland
city: Christchurch
country: New Zealand
facility: Christchurch Hospital
state: Canterbury
city: Hamilton
country: New Zealand
facility: Department of Gastroenterology Research
state: Waikato
city: Wellington
country: New Zealand
facility: P3 Research Limited
city: Bucuresti
country: Romania
facility: Spitalul Clinic Colentina
state: Sector 2
city: Zuerich
country: Switzerland
facility: Universitaetsspital Zuerich
city: Hull
country: United Kingdom
facility: Hull and East Yorkshire Hospitals NHS Trust
state: East Yorkshire
city: Cambridge
country: United Kingdom
facility: Addenbrooke's Hospital, Department of Gastroenterology
city: Glasgow
country: United Kingdom
facility: Glasgow Royal Infirmary
city: Hull
country: United Kingdom
facility: Pharmacy Department
city: London
country: United Kingdom
facility: Barts and The London NHS Trust
city: London
country: United Kingdom
facility: Royal Free Hospital (Royal Free London NHS Foundation Trust)
city: Newcastle-upon-Tyne
country: United Kingdom
facility: Royal Victoria Hospital
city: Wolverhampton
country: United Kingdom
facility: New Cross Hospital
city: Wolverhampton
country: United Kingdom
facility: Newcross Hospital-The Royal Wolverhampton Hospitals NHS Trust
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: Li C, Shoji S, Beebe J. Pharmacokinetics and C-reactive protein modelling of anti-interleukin-6 antibody (PF-04236921) in healthy volunteers and patients with autoimmune disease. Br J Clin Pharmacol. 2018 Sep;84(9):2059-2074. doi: 10.1111/bcp.13641. Epub 2018 Jun 25.
citation: Danese S, Vermeire S, Hellstern P, Panaccione R, Rogler G, Fraser G, Kohn A, Desreumaux P, Leong RW, Comer GM, Cataldi F, Banerjee A, Maguire MK, Li C, Rath N, Beebe J, Schreiber S. Randomised trial and open-label extension study of an anti-interleukin-6 antibody in Crohn's disease (ANDANTE I and II). Gut. 2019 Jan;68(1):40-48. doi: 10.1136/gutjnl-2017-314562. Epub 2017 Dec 15.