Pharmacokinetics/Pharmacodynamics Biomarker Study in Active Ulcerative Colitis Patients

A Phase 2a, Randomized, Double-blind, Sponsor Unblinded, Placebo-controlled, Multiple Dose Study To Evaluate The Pharmacodynamics, Pharmacokinetics And Safety Of Anrukinzumab In Subjects With Active Ulcerative Colitis

This study represents the first investigation of anrukinzumab in patients with active ulcerative colitis (UC) and will evaluate proof of mechanism by changes in the mechanism based biomarker (YKL 40) and pharmacodynamic biomarkers (fecal calprotectin, lactoferrin and hs-CRP). It will provide further assessment of the safety, tolerability, and pharmacokinetics (PK) by administration of multiple intravenous (IV) doses of anrukinzumab.

Study Overview

• Status: Completed
• Conditions: Colitis, Ulcerative
• Intervention / Treatment: Biological: Anrukinzumab; Biological: Anrukinzumab; Biological: Anrukinzumab; Other: placebo

• Study Type: Interventional
• Enrollment (Actual): 84
• Phase: Phase 2

Contacts and Locations

Study Locations

• Austria
  • Linz, Austria, 4020
    • Krankenhaus der Elisabethinen Linz GmbH
  • St. Poelten, Austria, 3100
    • Landesklinikum St. Poelten
  • Wien, Austria, 1090
    • AKH Wien Universitaetsklinik fuer Innere Medizin III
• Bulgaria
  • Ruse, Bulgaria, 7002
    • MBAL Ruse / MHAT Ruse, Terapevtichno, gastroenterologichno i hematologichno otdelenie
  • Sofia, Bulgaria, 1606
    • MBAL Voennomeditsinska Akademia / MMA HAT, Klinika po gastroenterologia i hepatologia
  • Sofia, Bulgaria, 1750
    • DKTs Sveta Anna, Gastroenterologichen cabinet
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4Z6
      • Heritage Medical Research Clinic - University Of Calgary
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 1M9
      • Vancouver Coastal Health - Vancouver General Hospital
    • Vancouver, British Columbia, Canada, V5Z 1M9
      • Vancouver General Hospital - The Gordon and Leslie Diamond Centre
  • Ontario
    • Kingston, Ontario, Canada, K7L 5G2
      • The Religious Hospitallers of St. Joseph of the Hotel Dieu of Kingston
    • Toronto, Ontario, Canada, M4N 3M5
      • Sunnybrook Health Sciences Centre
• France
  • Amiens Cedex 01, France, 80054
    • CHU Hopital Nord
  • Clichy, France, 92110
    • Hôpital Beaujon
  • Nantes CEDEX 1, France, 44093
    • CHU Hotel-Dieu
• Germany
  • Berlin, Germany, 10117
    • Charite - Campus Berlin Mitte
  • Heidelberg, Germany, 69120
    • Universitaetsklinikum Heidelberg
  • Kiel, Germany, 24105
    • Universitaetsklinikum Schleswig-Holstein, Campus Kiel
  • Minden, Germany, 32423
    • Gastroenterologische Gemeinschaftspraxis Minden
• Hungary
  • Budapest, Hungary, 1136
    • Pannonia Maganorvosi Centrum Kft.
  • Budapest, Hungary, 1125
    • Szent Janos Korhaz es Eszak-budai Egyesitett Korhazak/I. Belgyogyaszati-Gasztroenterologiai Osztaly
  • Szekszard, Hungary, 7100
    • Clinfan Kft.
• Netherlands
  • Amsterdam, Netherlands, 1081 HV
    • VU Medisch Centrum
  • Amsterdam, Netherlands, 1105 AZ
    • Academic Medical Center - University of Amsterdam, Dept. of Gastroenterology
  • Maastricht, Netherlands, 6229 HX
    • Academisch Ziekenhuis Maastricht
• Poland
  • Warszawa, Poland, 02-507
    • Centralny Szpital Kliniczny MSWiA, Klinika Chorob Wewnetrznych i Gastroenterologii
• Romania
  • Bucuresti, Romania, 010816
    • Sectia Clinica Medicina Interna II
• Spain
  • Barcelona, Spain, 08036
    • Hospital Clinic i Provincial de Barcelona
  • Madrid, Spain, 28007
    • Hospital General Universitario Gregorio Marañón
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35249
      • UAB Hospital Department of Pharmacy
    • Birmingham, Alabama, United States, 35233
      • UAB Hospital
    • Birmingham, Alabama, United States, 35233
      • The Kirkland Clinic
    • Birmingham, Alabama, United States, 35294
      • Administrative Offices
    • Birmingham, Alabama, United States, 35294
      • UAB ACIP
  • Arizona
    • Phoenix, Arizona, United States, 85013
      • Dedicated Phase I, Inc.
    • Phoenix, Arizona, United States, 85006
      • Arizona Surgical Center
  • California
    • Anaheim, California, United States, 92801
      • Anaheim Clinical Trials, LLC
    • Anaheim, California, United States, 92801
      • AGMG Endoscopy Center
    • Santa Ana, California, United States, 92705
      • West Coast Radiology Center
  • Connecticut
    • 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
    • Sanford, Florida, United States, 32771
      • International Clinical Research - US, LLC
  • Georgia
    • Marietta, Georgia, United States, 30060
      • Gastrointestinal Specialists of Georgia, PC
    • Marietta, Georgia, United States, 30067
      • GI Diagnostics
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • St. Dominic Hospital
    • Jackson, Mississippi, United States, 39202
      • Gastrointestinal Associates, PA
    • Jackson, Mississippi, United States, 39202
      • Gastrointestional Associates, PA
    • Tupelo, Mississippi, United States, 38801
      • North Mississippi Medical Center
    • Tupelo, Mississippi, United States, 38801
      • Digestive Health Specialists, PA
  • New York
    • Poughkeepsie, New York, United States, 12601
      • Premier Medical Group of the Hudson Valley
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27103
      • PMG Research of Winston-Salem
    • Winston-Salem, North Carolina, United States, 27103
      • Piedmont Gastroenterology Specialists
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • University Hospitals Case Medical Center - Division of Gastroenterology and Liver Disease
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Oklahoma Foundation for Digestive Research
    • Oklahoma City, Oklahoma, United States, 73104
      • OU Physicians Building
    • Oklahoma City, Oklahoma, United States, 73103
      • Wheeler and Stuckey, Inc.
  • Tennessee
    • Germantown, Tennessee, United States, 38138
      • Memphis Gastroenterology Group, PC
    • Memphis, Tennessee, United States, 38120
      • The West Clinic
    • Nashville, Tennessee, United States, 37203
      • Centennial Medical Center Physicians Park
    • Nashville, Tennessee, United States, 37203
      • Centennial Medical Center Tower Medical Imaging
    • Nashville, Tennessee, United States, 37203
      • Columbia Medical Group - The First Clinic Inc.
    • Nashville, Tennessee, United States, 37203
      • Radiology Alliance
  • Texas
    • Austin, Texas, United States, 78705
      • Professional Quality Research, Inc.
    • Austin, Texas, United States, 78757
      • Austin Endoscopy Center
    • Austin, Texas, United States, 78757
      • Austin Gastroenterology, PA
    • Houston, Texas, United States, 77081
      • Texas Center for Drug Development, Inc.
    • Round Rocks, Texas, United States, 78681
      • Austin Gastroenterology, PA
    • San Antonio, Texas, United States, 78229
      • Cardiology Clinic of San Antonio
    • San Antonio, Texas, United States, 78229
      • Gastroenterology Research of San Antonio
    • San Antonio, Texas, United States, 78229
      • San Antonio Endoscopy Center
  • Utah
    • Murray, Utah, United States, 84123
      • CNS Pharmacy
    • Salt Lake City, Utah, United States, 84132
      • University of Utah Hospital
    • Salt Lake City, Utah, United States, 84102
      • Alpine Medical Group
    • Salt Lake City, Utah, United States, 84107
      • Wasatch Clinical Research
    • Salt Lake City, Utah, United States, 84124
      • Wasatch Endoscopy Center
    • Salt Lake City, Utah, United States, 84084
      • RGL Medical Services

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or Female, Age >=18 and <=65 years
• Active ulcerative colitis (UC) beyond the rectum based upon Mayo Score
• women of childbearing potential with highly effective method of contraception

Exclusion Criteria:

• Indeterminate disease status, Crohn's disease, ischemic colitis, positive HIV, positive or history of tuberculosis infection, active enteric infections, transplant organ recipient, concomitant steroids, immunosuppressives or anti-TNFs.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1; 200 mg PF-05230917, Anrukinzumab active dose level	Biological: Anrukinzumab; 200 mg sterile liquid vial, administered intravenously, one-hour infusion on Day 1, Week 2, 4, 8, and 12; Other Names: PF-05230917; Biological: Anrukinzumab; 200 mg sterile liquid vial, dose level 400 mg administered intravenously, one-hour infusion on Day 1, Week 2, 4, 8, and 12; Other Names: PF-05230917; Biological: Anrukinzumab; 200 mg sterile liquid vial, dose level 600 mg administered intravenously, one-hour infusion on Day 1, Week 2, 4, 8, and 12 Note: dosing in the 600 mg arm will be delayed until the safety of the 200 mg and 400 mg arms has been reviewed.; Other Names: PF-05230917
Experimental: Arm 2; 400 mg PF-05230917, Anrukinzumab active dose level	Biological: Anrukinzumab; 200 mg sterile liquid vial, administered intravenously, one-hour infusion on Day 1, Week 2, 4, 8, and 12; Other Names: PF-05230917; Biological: Anrukinzumab; 200 mg sterile liquid vial, dose level 400 mg administered intravenously, one-hour infusion on Day 1, Week 2, 4, 8, and 12; Other Names: PF-05230917; Biological: Anrukinzumab; 200 mg sterile liquid vial, dose level 600 mg administered intravenously, one-hour infusion on Day 1, Week 2, 4, 8, and 12 Note: dosing in the 600 mg arm will be delayed until the safety of the 200 mg and 400 mg arms has been reviewed.; Other Names: PF-05230917
Experimental: Arm 3; 600 mg PF-05230917, Anrukinzumab active dose level	Biological: Anrukinzumab; 200 mg sterile liquid vial, administered intravenously, one-hour infusion on Day 1, Week 2, 4, 8, and 12; Other Names: PF-05230917; Biological: Anrukinzumab; 200 mg sterile liquid vial, dose level 400 mg administered intravenously, one-hour infusion on Day 1, Week 2, 4, 8, and 12; Other Names: PF-05230917; Biological: Anrukinzumab; 200 mg sterile liquid vial, dose level 600 mg administered intravenously, one-hour infusion on Day 1, Week 2, 4, 8, and 12 Note: dosing in the 600 mg arm will be delayed until the safety of the 200 mg and 400 mg arms has been reviewed.; Other Names: PF-05230917
Placebo Comparator: Arm 4; Matching placebo - administered at matching dose level 200 mg, 400 mg or 600 mg.	Other: placebo; 200 mg liquid sterile vial, administered at matching dose level 200 mg, 400 mg or 600 mg intravenously, one-hour infusion on Day 1, Week 2, 4, 8, and 12

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fold Change From Baseline in Fecal Calprotectin at Week 14	The fold change from baseline in fecal calprotectin at Week 14, is the ratio of the measurement of fecal calprotectin at Week 14 to baseline measurement; this was calculated as the change from baseline in natural log transformed fecal calprotectin at Week 14.	Baseline, Week 14

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Observed Plasma Concentration (Cmax) for Anrukinzumab	Maximum concentration observed during the dosing interval (2 weeks for day 1, 4 weeks for week 12).	Pre-dose to end of the dosing interval after Day 1, Week 12
Minimum Observed Plasma Trough Concentration (Cmin) for Anrukinzumab	Lowest concentration observed during the dosing interval (2 weeks for day 1, 4 weeks for week 12).	Pre-dose to end of the dosing interval after Day 1, Week 12
Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) for Anrukinzumab	Area under the plasma concentration curve from time zero to end of dosing interval (2 weeks) was reported.	Pre-dose, within 1 hour post-end of infusion on Day 1; Day 2, 4, 7, pre-dose on Week 2
Plasma Decay Half-Life (t1/2) for Anrukinzumab	Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.	Within 1 hour post-end of infusion on Week 12; Week 14, 16, 18, 20, 22, 24, 26, 28, 30, 32
Systemic Clearance (CL) for Anrukinzumab	CL is a quantitative measure of the rate at which a drug substance is removed from the body.	Pre-dose, within 1 hour post-end of infusion on Week 12; Week 14, 16, 18, 20, 22, 24, 26, 28, 30, 32
Volume of Distribution (Vz) for Anrukinzumab	Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug.	Pre-dose, within 1 hour post-end of infusion on Week 12; Week 14, 16, 18, 20, 22, 24, 26, 28, 30, 32
Fold Change From Baseline in Fecal Calprotectin at Week 2, 4, 8 and 12	The fold change from baseline in fecal calprotectin at post-baseline visit, is the ratio of the measurement of fecal calprotectin at post-baseline visit to baseline measurement; this was calculated as the change from baseline in natural log transformed fecal calprotectin at post-baseline visit.	Baseline, Week 2, 4, 8, 12
Total Interleukin-13 (IL-13) Level		Baseline, Day 2, 4, 7, Week 2, 4, 8, 12, 14, 16, 20, 24, 28, 32
Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)	An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to Week 32 that were absent before treatment or that worsened relative to pretreatment state. All causality AEs included SAEs as well as non-serious AEs, without regard to relationship to the study drug, which occurred during the trial.	Baseline up to Week 32
Number of Participants Who Discontinued From the Study Due to Adverse Events		Baseline up to Week 32
Number of Participants With Anti-drug Antibody (ADA) and Neutralizing Antibody	Neutralizing antibody was not analyzed as no participant had positive ADA samples.	Day 1, Week 4, 8, 12, 14, 16, 20, 24, 28, 32
Number of Participants With Change From Baseline in Endoscopic Subscore at Week 14	Mayo score is used to measure the disease activity of ulcerative colitis. Endoscopy or flexible sigmoidoscopy is a sub score of Mayo score. The score for endoscopic subscore ranges from 0 to 3, where higher score indicates more severe disease activity. Participant's score for endoscopy or flexible sigmoidoscopy at Week 14 was specified as improved (decrease), no change and worsened (increase) compared to their baseline score.	Baseline, Week 14

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Response Rate at Week 14	Clinical response rate is defined as percentage of participants with at least 3 point decrease from baseline in total Mayo score with at least 30% change along with 1 point decrease from baseline or absolute score of 0 or 1 in rectal bleeding. The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The Mayo score ranges from 0 to 12 points and consists of 4 subscores (stool frequency, rectal bleeding, findings on flexible sigmoidoscopy [endoscopy] and physician's global assessment), each subscore is graded from 0 to 3 with the higher score indicating more severe disease activity.	Week 14
Clinical Remission Rate at Week 14	Clinical remission rate is defined as percentage of participants with a total Mayo score less than or equal to 2, with no individual subscore greater than 1 at post baseline visit. The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The Mayo score ranges from 0 to 12 points and consists of 4 subscores (stool frequency, rectal bleeding, findings on flexible sigmoidoscopy and physician's global assessment), each subscore is graded from 0 to 3 with the higher score indicating more severe disease activity.	Week 14
Change From Baseline in Total Mayo Score at Week 14	The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The Mayo score ranges from 0 to 12 points and consists of 4 subscores (stool frequency, rectal bleeding, findings on flexible sigmoidoscopy [endoscopy] and physician's global assessment), each subscore is graded from 0 to 3 with the higher score indicating more severe disease activity.	Baseline, Week 14
Number of Participants With Change From Baseline in Stool Frequency at Week 14	Stool frequency is a sub score of Mayo score used to measure the disease activity of ulcerative colitis. The score for stool frequency ranges from 0 to 3, where higher score indicates more severe disease activity. Participant's score for stool frequency at Week 14 was specified as improved (decrease), no change and worsened (increase) compared to their baseline score.	Baseline, Week 14
Number of Participants With Change From Baseline in Rectal Bleeding at Week 14	Mayo score is used to measure the disease activity of ulcerative colitis. Rectal bleeding is a sub score of Mayo score. The score for rectal bleeding ranges from 0 to 3, where higher score indicates more severe disease activity. Participant's score for rectal bleeding at Week 14 was specified as improved (decrease), no change and worsened (increase) compared to their baseline score.	Baseline, Week 14

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

General Publications

• Reinisch W, Panes J, Khurana S, Toth G, Hua F, Comer GM, Hinz M, Page K, O'Toole M, Moorehead TM, Zhu H, Sun Y, Cataldi F. Anrukinzumab, an anti-interleukin 13 monoclonal antibody, in active UC: efficacy and safety from a phase IIa randomised multicentre study. Gut. 2015 Jun;64(6):894-900. doi: 10.1136/gutjnl-2014-308337. Epub 2015 Jan 7.

Helpful Links

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

Study record dates

Study Major Dates

• Study Start: March 1, 2011
• Primary Completion (Actual): April 1, 2013
• Study Completion (Actual): April 1, 2013

Study Registration Dates

• First Submitted: January 25, 2011
• First Submitted That Met QC Criteria: January 25, 2011
• First Posted (Estimate): January 26, 2011

Study Record Updates

• Last Update Posted (Estimate): November 18, 2014
• Last Update Submitted That Met QC Criteria: November 10, 2014
• Last Verified: November 1, 2014

More Information

Terms related to this study

• Keywords: Randomized; Double-blind; Active Ulcerative Colitis; Phase 2A; PK/PD Biomarker Study
• 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: B2421003; IMA-638 Anti-IL13 mAb; 2010-023762-49 (EudraCT Number)