A Study To Assess The Efficacy And Safety Of PF-04236921 In Subjects With Crohn's Disease Who Failed Anti-TNF Therapy (ANDANTE)

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)

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.

Study Overview

• Status: Completed
• Conditions: Crohn's Disease
• Intervention / Treatment: Drug: PF-04236921 SC injection; Drug: PF-04236921 SC injection; Drug: PF-04236921 SC injection

• Study Type: Interventional
• Enrollment (Actual): 250
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Fitzroy, Australia, VIC 3065
    • St. Vincent's Hospital Melbourne
  • New South Wales
    • Concord, New South Wales, Australia, 2139
      • Concord Repatriation General Hospital
    • Kingswood, New South Wales, Australia, 2747
      • Nepean Public Hospital
  • Queensland
    • Herston, Brisbane, Queensland, Australia, 4029
      • Royal Brisbane and Women'S Hospital
    • South Brisbane, Queensland, Australia, 4101
      • Mater Health Services
  • Victoria
    • Box Hill, Victoria, Australia, 3128
      • Eastern Health, Box Hill Hospital
    • Clayton, Victoria, Australia, 3168
      • Monash Medical Centre
    • Parkville, Victoria, Australia, 3050
      • The Royal Melbourne Hospital
• Belgium
  • Bruxelles, Belgium, 1000
    • CHU Saint-Pierre
  • Leuven, Belgium, 3000
    • UZ Leuven Pharmacy
  • Roeselare, Belgium, B-8800
    • An Spiessens H.-Hartziekenhuis Roeselare-Menen vzw
  • Vlaams Brabant
    • Leuven, Vlaams Brabant, Belgium, 3000
      • University Hospital Leuven
• Brazil
  • Curitiba, Brazil, 80810-040
    • Hospital Nossa Senhora Das Gracas
  • GO
    • Goiania, GO, Brazil, 74535-170
      • Instituto Goiano de Gastroenterologia e Endoscopia Digestiva Ltda.
    • Goiania, GO, Brazil, 74535-170
      • Clinica do Coracao Samaritano
    • Goiania, GO, Brazil, 74535-900
      • Center X Diagnosticos
  • RJ
    • Rio de Janeiro, RJ, Brazil, 21941-913
      • Hospital Universitário Fraga Filho da UFRJ
  • RS
    • Porto Alegre, RS, Brazil, 90610-000
      • Hospital São Lucas da PUCRS
  • SP
    • Santo Andre, SP, Brazil, 09060-650
      • Faculdade de Medicina do ABC
    • São Paulo, SP, Brazil, 05651-901
      • Hospital Israelita Albert Einstein
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4Z6
      • Heritage Medical Research Clinic - University of Calgary
  • Ontario
    • London, Ontario, Canada, N6A 5A5
      • London Health Science Centre - University Hospital
    • Toronto, Ontario, Canada, M5G 1X5
      • Mount Sinai Hospital
  • Quebec
    • Montreal, Quebec, Canada, H3A 1A1
      • McGill University Health Centre - Royal Victoria Hospital
• Czech Republic
  • Hradec Kralove, Czech Republic, 500 12
    • Hepato-Gastroenterologie HK, s.r.o.
  • Hradec Kralove, Czech Republic, 500 12
    • Medial Pharma s.r.o.,
  • Olomouc, Czech Republic, 775 20
    • Fakultni Nemocnice Olomouc
  • Prague, Czech Republic, 170 04
    • Klinicke centrum ISCARE I.V.F. - gastroenterologie
  • Praha 10, Czech Republic, 100 34
    • Fakultni nemocnice Kralovske Vinohrady
  • Praha 4, Czech Republic, 14021
    • Institut Klinicke A Experimentalni Mediciny
  • Praha 7, Czech Republic
    • IBD Clinical and Research centre
  • Usti nad Labem, Czech Republic, 40113
    • Krajska Zdravotni, a.s.
• Denmark
  • Aalborg, Denmark, 9100
    • Aalborg Sygehus
  • Aarhus C, Denmark, 8000
    • Aarhus Universitetshospital, Aarhus Sygehus Aarhus University Hospital
  • Herlev, Denmark, 2730
    • Gastroenheden
  • Hilleroed, Denmark, 3400
    • Kirurgisk Afdeling 0143
  • Hvidovre, Denmark, 2650
    • Hvidovre Hospital
  • Koebenhavn, Denmark, 2100
    • Rigshospitalet
  • Koebenhavn NV, Denmark, 2400
    • Afdeling I, Gastroenterologisk Sektion
  • Koege, Denmark, 4600
    • Medicinsk Afdeling, Gastroenterologisk Sektion
• France
  • Lille Cedex, France, 59037
    • Hopital Huriez, CHRU de Lille
  • Paris Cedex 12, France, 75571
    • Hopital Saint-Antoine - Service De Gastroenterologie
  • Vandoeuvre Les Nancy, France, 54500
    • Hôpital de Brabois
• Germany
  • Berlin, Germany, 12200
    • "Charite - Campus Benjamin Franklin
  • Hamburg, Germany, 20148
    • Praxis Dr. Howaldt
  • Kiel, Germany, 24105
    • Universitaetsklinikum Schleswig-Holstein
  • Minden, Germany, 32423
    • Gastroenterologische Gemeinschaftspraxis Minden
  • Regensburg, Germany, 93053
    • Universitaetsklinik Regensburg
  • Niedersachsen
    • Hannover, Niedersachsen, Germany, 30625
      • Medizinische Hochschule Hannover
• Greece
  • Athens, Greece, 12462
    • University General Hospital "Attikon"
  • Kolonaki Athens, Greece, 106 76
    • General Hospital of Athens "Evangelismos",1st Gastroenterology Department
• Hungary
  • Budapest, Hungary, 1136
    • Pannonia Maganorvosi Centrum Kft.
  • Budapest, Hungary, 1088
    • Semmelweis Egyetem II. Sz. Belgyogyaszati Klinika
  • Budapest, Hungary, 1125
    • Szent Janos Korhaz es Eszak-budai Egyesitett Korhazak./I. Belgyogyaszati-Gasztroenterologiai
  • Debrecen, Hungary, 4032
    • Debreceni Egyetem Orvos- es Egeszsegtudomanyi Centrum
  • Szeged, Hungary, 6720
    • Szegedi Tudomanyegyetem altalanos Orvostudomanyi Kar / I. sz. Belgyogyaszati Klinika
  • Szekszard, Hungary, 7100
    • Clinfan Kft.
• Ireland
  • Dublin, Ireland, 9
    • Beaumont Hospital
  • Dublin, Ireland, Dublin 4
    • National Virus Reference Laboratory
  • Dublin, Ireland, Dublin 4
    • Pathology, Haematology and Biochemistry Laboratories, St Vincent's Healthcare Group
  • Dublin, Ireland, Dublin 7
    • Mater Misericordiae Hospital, Department of Clinical Chemistry and Clinical Haematology
  • Dublin 4, Ireland
    • St. Vincents University Hospital
  • Galway, Ireland
    • University Hospital Galway
• Israel
  • Haifa, Israel, 3339419
    • Institute of Gastroenterology
  • Holon, Israel, 58100
    • The E. Wolfson Medical Center
  • Jerusalem, Israel, 91120
    • Hadassah Medical Center
  • Jerusalem, Israel, 91031
    • Shaare Zedek Medical Center
  • Kfar Saba, Israel, 44281
    • Dept of Gastroenterology & Hepatology
  • Petach Tikva, Israel, 49100
    • Rabin Medical Center, Beilinson Hospital
  • Tel Aviv, Israel, 64239
    • Tel Aviv Sourasky Medical Center
  • Zerifin, Israel, 70300
    • Assaf Harofeh Medical Center
  • Ramat Gan
    • Tel Hashomer, Ramat Gan, Israel, 52621
      • The Institute Of Gastroenterology & Liver Diseases
• Italy
  • Bologna, Italy, 40138
    • Azienda Ospedaliero Universitaria di Bologna Policlinico Sant'Orsola Malpighi
  • Padova, Italy, 35128
    • Azienda Ospedaliera - Università di Padova
  • Roma, Italy, 00133
    • Policlinico Tor Vergata
  • Roma, Italy, 00151
    • Azienda Ospedaliera San Camillo Forlanini
  • Roma, Italy, 00128
    • Università Campus Biomedico
  • Foggia
    • San Giovanni Rotondo Fg, Foggia, Italy, 71013
      • Casa Sollievo della Sofferenza/Div.Gastroenterologia Endoscopia Digestiva
  • Milano
    • Rozzano, Milano, Italy, 20089
      • Istituto Clinico Humanitas IRCCS
  • Province of Rome
    • Rome, Province of Rome, Italy, 00168
      • A. Gemelli University Hospital-Department of Medical Sciences - Division of Internal Medicine and
• New Zealand
  • Wellington, New Zealand, 6021
    • P3 Research Limited
  • Auckland
    • Milford, Auckland, New Zealand, 0620
      • Shakespeare Specialist Group
  • Canterbury
    • Christchurch, Canterbury, New Zealand, 8011
      • Christchurch Hospital
  • Waikato
    • Hamilton, Waikato, New Zealand, 3204
      • Department of Gastroenterology Research
• Romania
  • Sector 2
    • Bucuresti, Sector 2, Romania, 020125
      • Spitalul Clinic Colentina
• Switzerland
  • Zuerich, Switzerland, 8091
    • Universitaetsspital Zuerich
• United Kingdom
  • Cambridge, United Kingdom, CB2 0QQ
    • Addenbrooke's Hospital, Department of Gastroenterology
  • Glasgow, United Kingdom, G40SS
    • Glasgow Royal Infirmary
  • Hull, United Kingdom, HU3 2JZ
    • Pharmacy Department
  • London, United Kingdom, E1 1BB
    • Barts and the London NHS Trust
  • London, United Kingdom, NW3 2QG
    • Royal Free Hospital (Royal Free London NHS Foundation Trust)
  • Newcastle-upon-Tyne, United Kingdom, NE1 4LP
    • Royal Victoria Hospital
  • Wolverhampton, United Kingdom, WV10 0QP
    • New Cross Hospital
  • Wolverhampton, United Kingdom, WV69AT
    • Newcross Hospital-The Royal Wolverhampton Hospitals NHS Trust
  • East Yorkshire
    • Hull, East Yorkshire, United Kingdom, HU3 2JZ
      • Hull and East Yorkshire Hospitals NHS Trust
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham
    • Birmingham, Alabama, United States, 35249
      • UAB Hospital
  • Arizona
    • Scottsdale, Arizona, United States, 85260
      • Digestive Health Research Unit
    • Scottsdale, Arizona, United States, 85258
      • Simon Medical Imaging
    • Tucson, Arizona, United States, 85712
      • Adobe Clinical Research, LLC
    • Tucson, Arizona, United States, 85712
      • Radiology Ltd
  • California
    • San Francisco, California, United States, 94115
      • University of California - San Francisco
    • San Francisco, California, United States, 94115
      • UCSF Endoscopy Unit at Mount Zion
    • San Francisco, California, United States, 94115
      • University of California San Francisco at Mount Zion
  • Colorado
    • Denver, Colorado, United States, 80222
      • Rocky Mountain Clinical Research, LLC
    • Lakewood, Colorado, United States, 80215
      • Rocky Mountain Gastroenterology
    • Lakewood, Colorado, United States, 80215
      • Rocky Mountain Gastroenterology Associates
    • Littleton, Colorado, United States, 80120
      • Arapahoe Gastroenterology, PC
  • Connecticut
    • Guilford, Connecticut, United States, 06437
      • Endoscopy Center of Connecticut, LLC
    • Hamden, Connecticut, United States, 06518
      • Medical Research Center of Connecticut, LLC
    • Hamden, Connecticut, United States, 06518
      • Gastroenterology Center of Connecticut, PC
    • Hamden, Connecticut, United States, 06518
      • Endoscopy Center of Connecticut, LLC
  • Florida
    • Clearwater, Florida, United States, 33765
      • Clinical Research of West Florida, Inc.
    • Crystal River, Florida, United States, 34429
      • Gastroenterology Associates
    • Inverness, Florida, United States, 34452
      • Nature Coast Clinical Research
    • Inverness, Florida, United States, 34453
      • Suncoast Endoscopy Center
    • New Port Richey, Florida, United States, 34653
      • Advanced Research Institute, Inc.
    • Sanford, Florida, United States, 32771
      • International Clinical Research - US, LLC
  • Georgia
    • Decatur, Georgia, United States, 30033
      • Atlanta Center for Gastroenterology, P.C.
    • Decatur, Georgia, United States, 30033
      • Atlanta Endoscopy Center
    • Decatur, Georgia, United States, 30033
      • Decatur Health Imaging
    • Marietta, Georgia, United States, 30060
      • Gastrointestinal Specialists of Georgia, PC
    • Marietta, Georgia, United States, 30067
      • GI Diagnostics
  • Illinois
    • Arlington Heights, Illinois, United States, 60005
      • Illinois Gastroenterology Group, LLC
    • Chicago, Illinois, United States, 60637
      • The University Of Chicago
    • Chicago, Illinois, United States, 60637
      • The University of Chicago Medical Center
    • Chicago, Illinois, United States, 60637
      • The University of Chicago Medical Center (UCMC)
    • Chicago, Illinois, United States, 60637
      • The University of Chicago Medical
    • Evanston, Illinois, United States, 60201
      • Northshore University Health System
    • Glenview, Illinois, United States, 60025
      • Glenbrook Hospital Outpatient Pharmacy
    • Glenview, Illinois, United States, 60026
      • Glenbrook Hospital
  • Indiana
    • Anderson, Indiana, United States, 46016
      • Central Indiana Gastroenterology Group
    • Anderson, Indiana, United States, 46016
      • Saint John's Research Institute
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • University of Kentucky
    • Louisville, Kentucky, United States, 40202
      • University of Louisville
    • Louisville, Kentucky, United States, 40202
      • University Of Louisville Research Foundation
    • Louisville, Kentucky, United States, 40202
      • University Of Louisville Healthcare Outpatient Center
  • Maryland
    • Annapolis, Maryland, United States, 21401
      • Investigative Clinical Research
    • Annapolis, Maryland, United States, 21401
      • Digestive Disorders Associates
    • Annapolis, Maryland, United States, 21401
      • Disgestive Disorders Associates
    • Annapolis, Maryland, United States, 21401
      • Maryland Diagnostics & Therapeutic Endo Center
  • Massachusetts
    • Brockton, Massachusetts, United States, 02302
      • Commonwealth Clinical Studies
    • Fall River, Massachusetts, United States, 02721
      • Prima CARE, PC
  • Michigan
    • Ann Arbor, Michigan, United States, 48106
      • St. Joseph Mercy Hospital
    • Grand Rapids, Michigan, United States, 49546
      • East Valley Endoscopy
    • Wyoming, Michigan, United States, 49519
      • Metro Health Hospital
    • Wyoming, Michigan, United States, 49519
      • Gastroenterology Associates of Western Michigan
    • Wyoming, Michigan, United States, 49519
      • Metro Health Hospital Endoscopy Unit
    • Ypsilanti, Michigan, United States, 48197
      • Huron Gastroenterology Associates
    • Ypsilanti, Michigan, United States, 48197
      • St. Joseph Mercy Hospital
  • Minnesota
    • Plymouth, Minnesota, United States, 55446
      • Minnesota Gastroenterology, PA
  • New York
    • New York, New York, United States, 10029
      • Mount Sinai School of Medicine
    • New York, New York, United States, 10065
      • New York Presbyterian Hospital
    • New York, New York, United States, 10021
      • Weill Cornell Medical College of Cornell University
    • New York, New York, United States, 10065
      • New York Presbyterian Hospital - Weill Cornell Medical College Investigational Pharmacy
    • New York, New York, United States, 10065
      • Weill Cornell Imaging at New York Presbyterian Hospital
    • New York, New York, United States, 10021
      • Weill Cornell Medical College of Cornell University-Greenberg
    • New York, New York, United States, 10028
      • Present Chapman, Steinlauf and Marion
    • New York, New York, United States, 10128
      • Arthur asher Kornbluth, MD PC
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27103
      • PMG Research of Winston-Salem
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73102
      • Oklahoma Foundation for Digestive Research
    • Oklahoma City, Oklahoma, United States, 73104
      • Colonoscopy and X-rays: OU Physicians Building
    • Oklahoma City, Oklahoma, United States, 73103
      • Pharmacy: Wheeler and Stuckey, Inc.
    • Tulsa, Oklahoma, United States, 74104
      • Options Health Research, LLC
    • Tulsa, Oklahoma, United States, 74104
      • Hillcrest Medical Center
    • Tulsa, Oklahoma, United States, 74104
      • Hillcrest Medical Center Endoscopy
    • Tulsa, Oklahoma, United States, 74104
      • Utica Park Clinic X-Ray
    • Tulsa, Oklahoma, United States, 74137-4200
      • Advanced Imaging
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15243
      • Research Protocol Management Specialists
    • Pittsburgh, Pennsylvania, United States, 15243
      • Pittsburgh Gastroenterology Associates
  • Rhode Island
    • East Providence, Rhode Island, United States, 02915
      • Pharma Resource
    • Warwick, Rhode Island, United States, 02886
      • Omega Medical Research
  • Tennessee
    • Germantown, Tennessee, United States, 38138
      • Gastro One
    • Nashville, Tennessee, United States, 37212
      • Vanderbilt University Medical Center
  • Texas
    • Austin, Texas, United States, 78705
      • Professional Quality Research, Inc.
    • Houston, Texas, United States, 77030
      • The University of Texas Health Science Center at Houston
    • Houston, Texas, United States, 77030
      • Memorial Hermann Hospital
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine - Baylor Medical Center
    • Houston, Texas, United States, 77030
      • The University of Texas Medical School at Houston
    • Houston, Texas, United States, 77030
      • Ertan Digestive Disease Center
    • Houston, Texas, United States, 77004
      • Diagnostic Clinic of Houston, PA
    • Houston, Texas, United States, 77004
      • Houston Hospital for Specialized Surgery (Endoscopy only)
    • Houston, Texas, United States, 77030
      • Baylor Clinic (Drug Storage)
    • Houston, Texas, United States, 77036
      • Physicians Endoscopy Center (Colonoscopy)
    • Southlake, Texas, United States, 76092
      • Texas Digestive Disease Consultants
    • Sugar Land, Texas, United States, 77478
      • One Step Diagnostic (X-Ray)
    • Sugar Land, Texas, United States, 77479
      • Pioneer Research Solutions, Inc. (Admin. Office)
    • SugarLand, Texas, United States, 77479
      • Pioneer Research Solutions, Inc.
    • Tyler, Texas, United States, 75701
      • Digestive Health Specialists of Tyler
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • University of Utah HSC
  • Virginia
    • Richmond, Virginia, United States, 23298
      • Virginia Commonwealth University
    • Richmond, Virginia, United States, 23298-0341
      • Virginia Commonwealth University
    • Richmond, Virginia, United States, 93298-5028
      • VCU Medical Investigational Drug Service (IDS)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo- SC injection	Drug: PF-04236921 SC injection; Placebo delivered SC, 2 doses separated by 4 weeks; Drug: PF-04236921 SC injection; Drug dose level 1 delivered SC, 2 doses separated by 4 weeks; Drug: PF-04236921 SC injection; Drug dose level 2 delivered SC, 2 doses separated by 4 weeks
Experimental: Drug Dose level 1 - SC injection	Drug: PF-04236921 SC injection; Placebo delivered SC, 2 doses separated by 4 weeks; Drug: PF-04236921 SC injection; Drug dose level 1 delivered SC, 2 doses separated by 4 weeks; Drug: PF-04236921 SC injection; Drug dose level 2 delivered SC, 2 doses separated by 4 weeks
Experimental: Drug Dose level 2 - SC injection	Drug: PF-04236921 SC injection; Placebo delivered SC, 2 doses separated by 4 weeks; Drug: PF-04236921 SC injection; Drug dose level 1 delivered SC, 2 doses separated by 4 weeks; Drug: PF-04236921 SC injection; Drug dose level 2 delivered SC, 2 doses separated by 4 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	CDAI-70 response was defined as a decrease in CDAI score of 70 or greater from baseline. The proportions of participants with CDAI-70 response at Week 8 were compared between placebo and PF-04236921 10 mg/50 mg. CDAI is used to quantify the symptoms of patients with Crohn's Disease. CDAI evaluates 8 Crohn's disease-related variables during a 1-week assessment period, yielding a composite score greater than or equal to (>=) 0 and without an upper limit. Many clinical trials use the endpoint for response as a 70 or greater point decrease in CDAI and clinical remission is often defined as a CDAI score below 150. The Outcome included a Generalized linear mixed model analyses which incorporated longitudinal data for each subject, and the same model is used for estimate (least squares mean) and statistical analysis (mean difference).	Baseline and Week 8
The CDAI-70 Response Rate at Week 8 in Participants Who Received Placebo and PF-04236921 200 mg	CDAI-70 response was defined as a decrease in CDAI score of 70 or greater from baseline. The proportions of participants with CDAI-70 response at Week 8 were compared between placebo and PF-04236921 200 mg. CDAI is used to quantify the symptoms of patients with Crohn's Disease. CDAI evaluates 8 Crohn's disease-related variables during a 1-week assessment period, yielding a composite score >=0 and without an upper limit. Many clinical trials use the endpoint for response as a 70 or greater point decrease in CDAI and clinical remission is often defined as a CDAI score below 150. The Outcome included a Generalized linear mixed model analyses which incorporated longitudinal data for each subject, and the same model is used for estimate (least squares mean) and statistical analysis (mean difference). Since the inputs in the model included different Analysis Population than in Outcome Measure 1, that will yield different estimates for placebo for the two different models.	Baseline and Week 8
The CDAI-70 Response Rate at Week 12 in Participants Who Received Placebo, PF-04236921 10 mg and PF-04236921 50 mg	CDAI-70 response was defined as a decrease in CDAI score of 70 or greater from baseline. The proportions of participants with CDAI-70 response at Week 12 were compared between placebo and and PF-04236921 10 mg/50 mg. CDAI is used to quantify the symptoms of patients with Crohn's Disease. CDAI evaluates 8 Crohn's disease-related variables during a 1-week assessment period, yielding a composite score >=0 and without an upper limit. Many clinical trials use the endpoint for response as a 70 or greater point decrease in CDAI and clinical remission is often defined as a CDAI score below 150. The Outcome included a Generalized linear mixed model analyses which incorporated longitudinal data for each subject, and the same model is used for estimate (least squares mean) and statistical analysis (mean difference).	Baseline and Week 12
The CDAI-70 Response Rate at Week 12 in Participants Who Received Placebo and PF-04236921 200 mg	CDAI-70 response was defined as a decrease in CDAI score of 70 or greater from baseline. The proportions of participants with CDAI-70 response at Week 12 were compared between placebo and PF-04236921 200 mg. CDAI is used to quantify the symptoms of patients with Crohn's Disease. CDAI evaluates 8 Crohn's disease-related variables during a 1-week assessment period, yielding a composite score >=0 and without an upper limit. Many clinical trials use the endpoint for response as a 70 or greater point decrease in CDAI and clinical remission is often defined as a CDAI score below 150. The Outcome included a Generalized linear mixed model analyses which incorporated longitudinal data for each subject, and the same model is used for estimate (least squares mean) and statistical analysis (mean difference). Since the inputs in the model included different Analysis Population than in Outcome Measure 3, that will yield different estimates for placebo for the two different models.	Baseline and Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The CDAI-70 Response Rate Over Time in Participants Who Received Placebo, PF-04236921 10 mg and PF-04236921 50 mg	CDAI-70 response was defined as a decrease in CDAI score of 70 or greater from baseline. The proportions of participants with CDAI-70 response were compared between placebo and PF-04236921 10 mg/50 mg. CDAI is used to quantify the symptoms of patients with Crohn's Disease. CDAI evaluates 8 Crohn's disease-related variables during a 1-week assessment period, yielding a composite score >=0 and without an upper limit. Many clinical trials use the endpoint for response as a 70 or greater point decrease in CDAI and clinical remission is often defined as a CDAI score below 150. The Outcome included a Generalized linear mixed model analyses which incorporated longitudinal data for each subject, and the same model is used for estimate (least squares mean) and statistical analysis (mean difference).	Baseline and Weeks 2, 4, 6, and 10
The CDAI-70 Response Rate Over Time in Participants Who Received Placebo and PF-04236921 200 mg	CDAI-70 response was defined as a decrease in CDAI score of 70 or greater from baseline. The proportions of participants with CDAI-70 response were compared between placebo and PF-04236921 200 mg. CDAI is used to quantify the symptoms of patients with Crohn's Disease. CDAI evaluates 8 Crohn's disease-related variables during a 1-week assessment period, yielding a composite score >=0 and without an upper limit. Many clinical trials use the endpoint for response as a 70 or greater point decrease in CDAI and clinical remission is often defined as a CDAI score below 150. The Outcome included a Generalized linear mixed model analyses which incorporated longitudinal data for each subject, and the same model is used for estimate (least squares mean) and statistical analysis (mean difference). Since the inputs in the model included different Analysis Population than in Outcome Measure 5, that will yield different estimates for placebo for the two different models.	Baseline and Weeks 2, 4, 6, and 10
The CDAI Remission Rate Over Time in Participants Who Received Placebo, PF-04236921 10 mg and PF-04236921 50 mg	CDAI remission rate was defined as an absolute CDAI score less than (<) 150. The proportions of participants with CDAI remission were compared between placebo and PF-04236921 10 mg/50 mg. CDAI is used to quantify the symptoms of patients with Crohn's Disease. CDAI evaluates 8 Crohn's disease-related variables during a 1-week assessment period, yielding a composite score >=0 and without an upper limit. Many clinical trials use the endpoint for response as a 70 or greater point decrease in CDAI and clinical remission is often defined as a CDAI score below 150. The Outcome included a Generalized linear mixed model analyses which incorporated longitudinal data for each subject, and the same model is used for estimate (least squares mean) and statistical analysis (mean difference).	Baseline and Weeks 2, 4, 6, 8, 10, and 12
The CDAI Remission Rate Over Time in Participants Who Received Placebo and PF-04236921 200 mg	CDAI remission rate was defined as an absolute CDAI score <150. The proportions of participants with CDAI remission were compared between placebo and PF-04236921 200 mg. CDAI is used to quantify the symptoms of patients with Crohn's Disease. CDAI evaluates 8 Crohn's disease-related variables during a 1-week assessment period, yielding a composite score >=0 and without an upper limit. Many clinical trials use the endpoint for response as a 70 or greater point decrease in CDAI and clinical remission is often defined as a CDAI score below 150. The Outcome included a Generalized linear mixed model analyses which incorporated longitudinal data for each subject, and the same model is used for estimate (least squares mean) and statistical analysis (mean difference). Since the inputs in the model included different Analysis Population than in Outcome Measure 7, that will yield different estimates for placebo for the two different models.	Baseline and Weeks 2, 4, 6, 8, 10, and 12
The CDAI-100 Response Rate Over Time in Participants Who Received Placebo, PF-04236921 10 mg and PF-04236921 50 mg	CDAI-100 response was defined as a decrease in CDAI score of 100 or greater from baseline. The proportions of participants with CDAI-100 response at Week 12 were compared between placebo and PF-04236921 10 mg/50 mg. CDAI is used to quantify the symptoms of patients with Crohn's Disease. CDAI evaluates 8 Crohn's disease-related variables during a 1-week assessment period, yielding a composite score >=0 and without an upper limit. Many clinical trials use the endpoint for response as a 70 or greater point decrease in CDAI and clinical remission is often defined as a CDAI score below 150. The Outcome included a Generalized linear mixed model analyses which incorporated longitudinal data for each subject, and the same model is used for estimate (least squares mean) and statistical analysis (mean difference).	Baseline and Weeks 2, 4, 6, 8, 10, and 12
The CDAI-100 Response Rate Over Time in Participants Who Received Placebo and PF-04236921 200 mg	CDAI-100 response was defined as a decrease in CDAI score of 100 or greater from baseline. The proportions of participants with CDAI-100 response at Week 12 were compared between placebo and PF-04236921 200 mg. CDAI is used to quantify the symptoms of patients with Crohn's Disease. CDAI evaluates 8 Crohn's disease-related variables during a 1-week assessment period, yielding a composite score >=0 and without an upper limit. Many clinical trials use the endpoint for response as a 70 or greater point decrease in CDAI and clinical remission is often defined as a CDAI score below 150. The Outcome included a Generalized linear mixed model analyses which incorporated longitudinal data for each subject, and the same model is used for estimate (least squares mean) and statistical analysis (mean difference). Since the inputs in the model included different Analysis Population than in Outcome Measure 9, that will yield different estimates for placebo for the two different models.	Baseline and Weeks 2, 4, 6, 8, 10, and 12
Change From Baseline in CDAI Score Over Time in Participants Who Received Placebo, PF-04236921 10 mg and PF-04236921 50 mg	CDAI evaluates 8 Crohn's disease-related variables during a 1-week assessment period, yielding a composite score >=0 and without an upper limit, and higher score indicate more severe disease. The Outcome included a Linear mixed model analyses which incorporated longitudinal data for each subject, and the same model is used for estimate (least squares mean) and statistical analysis (mean difference).	Baseline and Weeks 2, 4, 6, 8, 10, and 12
Change From Baseline in CDAI Score Over Time in Participants Who Received Placebo and PF-04236921 200 mg	CDAI evaluates 8 Crohn's disease-related variables during a 1-week assessment period, yielding a composite score >=0 and without an upper limit, and higher score indicate more severe disease. The Outcome included a Linear mixed model analyses which incorporated longitudinal data for each subject, and the same model is used for estimate (least squares mean) and statistical analysis (mean difference). Since the inputs in the model included different Analysis Population than in Outcome Measure 11, that will yield different estimates for placebo for the two different models.	Baseline and Weeks 2, 4, 6, 8, 10, and 12
Percentages of Participants With Confirmed Positive Anti-drug Antibodies (ADAs)	The percentage of participants with confirmed positive ADA was summarized for each treatment arm. ADA positive was defined as ADA titer defined as ADA titer (ie, the reciprocal of the highest dilution that gives a value equivalent to the cut point of the assay) >= 4.32.	At baseline (Day 1) and at Weeks 4, 8, 12, 16, 24, 32 and 40
Percentages of Participants With Confirmed Positive Neutralizing Antibodies (NAbs)	The percentage of participants with confirmed positive NAbs was summarized for each treatment arm. Only ADA positive samples were analyzed for Nab. A multi-tiered approach was utilized to detect NAbs. NAb serum samples were screened at tier one, and those found presumptively NAb positive was further tested with the confirmatory assay (tier two). The percentage of subjects with confirmed positive NAbs was summarized for each treatment.	At baseline (Day 1) and at Weeks 4, 8, 12, 16, 24, 32 and 40
Serum PF-04236921 Concentration Over Time		Day 1 (predose), and at Weeks 2, 4 (Day 28, predose), 8, 10, 12, 16, 20, 24, 28, 32, 36, and 40
Number of Participants Who Withdrew From the Study Due to Treatment-emergent Adverse Events (AEs)	An AE was any untoward medical occurrence without regard to causality in a participant who received study drug. Treatment-emergent were events between first dose of treatment and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state.	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)

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

General Publications

• 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.
• 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.

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start: February 1, 2011
• Primary Completion (Actual): September 1, 2014
• Study Completion (Actual): February 1, 2015

Study Registration Dates

• First Submitted: January 31, 2011
• First Submitted That Met QC Criteria: January 31, 2011
• First Posted (Estimate): February 2, 2011

Study Record Updates

• Last Update Posted (Estimate): January 21, 2016
• Last Update Submitted That Met QC Criteria: December 14, 2015
• Last Verified: December 1, 2015

More Information

Terms related to this study

• Keywords: safety; pharmacokinetics; efficacy; pharmacodynamics; Crohn's Disease; Crohn's Disease Activity Index (CDAI)
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Intestinal Diseases; Inflammatory Bowel Diseases; Crohn Disease
• Other Study ID Numbers: B0151003; 2010-023034-23 (EudraCT Number); ANDANTE (Other Identifier: Alias Study Number)