Pharmacokinetics/Pharmacodynamics Biomarker Study in Active Ulcerative Colitis Patients
- Conditions
- Colitis, Ulcerative
- Interventions
- Biological: AnrukinzumabOther: placebo
- Registration Number
- NCT01284062
- Lead Sponsor
- Pfizer
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 84
- 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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm 2 Anrukinzumab 400 mg PF-05230917, Anrukinzumab active dose level Arm 4 placebo Matching placebo - administered at matching dose level 200 mg, 400 mg or 600 mg. Arm 1 Anrukinzumab 200 mg PF-05230917, Anrukinzumab active dose level Arm 3 Anrukinzumab 600 mg PF-05230917, Anrukinzumab active dose level
- Primary Outcome Measures
Name Time Method Fold Change From Baseline in Fecal Calprotectin at Week 14 Baseline, 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.
- Secondary Outcome Measures
Name Time Method Volume of Distribution (Vz) for Anrukinzumab 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 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.
Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) Baseline up to Week 32 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.
Number of Participants Who Discontinued From the Study Due to Adverse Events Baseline up to Week 32 Plasma Decay Half-Life (t1/2) for Anrukinzumab Within 1 hour post-end of infusion on Week 12; Week 14, 16, 18, 20, 22, 24, 26, 28, 30, 32 Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
Maximum Observed Plasma Concentration (Cmax) for Anrukinzumab Pre-dose to end of the dosing interval after Day 1, Week 12 Maximum concentration observed during the dosing interval (2 weeks for day 1, 4 weeks for week 12).
Minimum Observed Plasma Trough Concentration (Cmin) for Anrukinzumab Pre-dose to end of the dosing interval after Day 1, Week 12 Lowest concentration observed during the dosing interval (2 weeks for day 1, 4 weeks for week 12).
Number of Participants With Change From Baseline in Endoscopic Subscore at Week 14 Baseline, 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.
Number of Participants With Anti-drug Antibody (ADA) and Neutralizing Antibody Day 1, Week 4, 8, 12, 14, 16, 20, 24, 28, 32 Neutralizing antibody was not analyzed as no participant had positive ADA samples.
Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) for Anrukinzumab Pre-dose, within 1 hour post-end of infusion on Day 1; Day 2, 4, 7, pre-dose on Week 2 Area under the plasma concentration curve from time zero to end of dosing interval (2 weeks) was reported.
Systemic Clearance (CL) for Anrukinzumab Pre-dose, within 1 hour post-end of infusion on Week 12; Week 14, 16, 18, 20, 22, 24, 26, 28, 30, 32 CL is a quantitative measure of the rate at which a drug substance is removed from the body.
Fold Change From Baseline in Fecal Calprotectin at Week 2, 4, 8 and 12 Baseline, Week 2, 4, 8, 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.
Total Interleukin-13 (IL-13) Level Baseline, Day 2, 4, 7, Week 2, 4, 8, 12, 14, 16, 20, 24, 28, 32
Trial Locations
- Locations (75)
CHU Hotel-Dieu
🇫🇷Nantes CEDEX 1, France
Medical Research Center of Connecticut, LLC
🇺🇸Hamden, Connecticut, United States
Endoscopy Center of Connecticut, LLC
🇺🇸Hamden, Connecticut, United States
DKTs Sveta Anna, Gastroenterologichen cabinet
🇧🇬Sofia, Bulgaria
International Clinical Research - US, LLC
🇺🇸Sanford, Florida, United States
AGMG Endoscopy Center
🇺🇸Anaheim, California, United States
Anaheim Clinical Trials, LLC
🇺🇸Anaheim, California, United States
Gastrointestinal Specialists of Georgia, PC
🇺🇸Marietta, Georgia, United States
Texas Center for Drug Development, Inc.
🇺🇸Houston, Texas, United States
Cardiology Clinic of San Antonio
🇺🇸San Antonio, Texas, United States
RGL Medical Services
🇺🇸Salt Lake City, Utah, United States
Alpine Medical Group
🇺🇸Salt Lake City, Utah, United States
Wasatch Endoscopy Center
🇺🇸Salt Lake City, Utah, United States
Digestive Health Specialists, PA
🇺🇸Tupelo, Mississippi, United States
North Mississippi Medical Center
🇺🇸Tupelo, Mississippi, United States
Gastroenterology Research of San Antonio
🇺🇸San Antonio, Texas, United States
University Hospitals Case Medical Center - Division of Gastroenterology and Liver Disease
🇺🇸Cleveland, Ohio, United States
Centennial Medical Center Tower Medical Imaging
🇺🇸Nashville, Tennessee, United States
Columbia Medical Group - The First Clinic Inc.
🇺🇸Nashville, Tennessee, United States
San Antonio Endoscopy Center
🇺🇸San Antonio, Texas, United States
Wasatch Clinical Research
🇺🇸Salt Lake City, Utah, United States
Sunnybrook Health Sciences Centre
🇨🇦Toronto, Ontario, Canada
The Religious Hospitallers of St. Joseph of the Hotel Dieu of Kingston
🇨🇦Kingston, Ontario, Canada
Arizona Surgical Center
🇺🇸Phoenix, Arizona, United States
Dedicated Phase I, Inc.
🇺🇸Phoenix, Arizona, United States
Wheeler and Stuckey, Inc.
🇺🇸Oklahoma City, Oklahoma, United States
Oklahoma Foundation for Digestive Research
🇺🇸Oklahoma City, Oklahoma, United States
OU Physicians Building
🇺🇸Oklahoma City, Oklahoma, United States
The Kirkland Clinic
🇺🇸Birmingham, Alabama, United States
Administrative Offices
🇺🇸Birmingham, Alabama, United States
UAB Hospital
🇺🇸Birmingham, Alabama, United States
UAB Hospital Department of Pharmacy
🇺🇸Birmingham, Alabama, United States
UAB ACIP
🇺🇸Birmingham, Alabama, United States
West Coast Radiology Center
🇺🇸Santa Ana, California, United States
Gastroenterology Center of Connecticut, PC
🇺🇸Hamden, Connecticut, United States
GI Diagnostics
🇺🇸Marietta, Georgia, United States
Gastrointestinal Associates, PA
🇺🇸Jackson, Mississippi, United States
St. Dominic Hospital
🇺🇸Jackson, Mississippi, United States
Premier Medical Group of the Hudson Valley
🇺🇸Poughkeepsie, New York, United States
The West Clinic
🇺🇸Memphis, Tennessee, United States
Memphis Gastroenterology Group, PC
🇺🇸Germantown, Tennessee, United States
Centennial Medical Center Physicians Park
🇺🇸Nashville, Tennessee, United States
Radiology Alliance
🇺🇸Nashville, Tennessee, United States
Austin Gastroenterology, PA
🇺🇸Round Rocks, Texas, United States
CNS Pharmacy
🇺🇸Murray, Utah, United States
University of Utah Hospital
🇺🇸Salt Lake City, Utah, United States
Landesklinikum St. Poelten
🇦🇹St. Poelten, Austria
AKH Wien Universitaetsklinik fuer Innere Medizin III
🇦🇹Wien, Austria
Krankenhaus der Elisabethinen Linz GmbH
🇦🇹Linz, Austria
MBAL Voennomeditsinska Akademia / MMA HAT, Klinika po gastroenterologia i hepatologia
🇧🇬Sofia, Bulgaria
MBAL Ruse / MHAT Ruse, Terapevtichno, gastroenterologichno i hematologichno otdelenie
🇧🇬Ruse, Bulgaria
Vancouver Coastal Health - Vancouver General Hospital
🇨🇦Vancouver, British Columbia, Canada
Vancouver General Hospital - The Gordon and Leslie Diamond Centre
🇨🇦Vancouver, British Columbia, Canada
Heritage Medical Research Clinic - University of Calgary
🇨🇦Calgary, Alberta, Canada
CHU Hopital Nord
🇫🇷Amiens Cedex 01, France
Hopital Beaujon
🇫🇷Clichy, France
Gastroenterologische Gemeinschaftspraxis Minden
🇩🇪Minden, Germany
Charite - Campus Berlin Mitte
🇩🇪Berlin, Germany
Universitaetsklinikum Heidelberg
🇩🇪Heidelberg, Germany
Universitaetsklinikum Schleswig-Holstein, Campus Kiel
🇩🇪Kiel, Germany
Pannonia Maganorvosi Centrum Kft.
ðŸ‡ðŸ‡ºBudapest, Hungary
Szent Janos Korhaz es Eszak-budai Egyesitett Korhazak/I. Belgyogyaszati-Gasztroenterologiai Osztaly
ðŸ‡ðŸ‡ºBudapest, Hungary
VU Medisch Centrum
🇳🇱Amsterdam, Netherlands
Academic Medical Center - University of Amsterdam, Dept. of Gastroenterology
🇳🇱Amsterdam, Netherlands
Clinfan Kft.
ðŸ‡ðŸ‡ºSzekszard, Hungary
Centralny Szpital Kliniczny MSWiA, Klinika Chorob Wewnetrznych i Gastroenterologii
🇵🇱Warszawa, Poland
Academisch Ziekenhuis Maastricht
🇳🇱Maastricht, Netherlands
Sectia Clinica Medicina Interna II
🇷🇴Bucuresti, Romania
Hospital General Universitario Gregorio Marañon
🇪🇸Madrid, Spain
Hospital Clinic I Provincial de Barcelona
🇪🇸Barcelona, Spain
Gastrointestional Associates, PA
🇺🇸Jackson, Mississippi, United States
Piedmont Gastroenterology Specialists
🇺🇸Winston-Salem, North Carolina, United States
Austin Endoscopy Center
🇺🇸Austin, Texas, United States
PMG Research of Winston-Salem
🇺🇸Winston-Salem, North Carolina, United States
Professional Quality Research, Inc.
🇺🇸Austin, Texas, United States