Clinical trial NCT01284062: Pharmacokinetics/Pharmacodynamics Biomarker Study in Active Ulcerative Colitis Patients
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Colitis, Ulcerative
Keywords: Active Ulcerative Colitis
Phase 2A
Double-blind
Randomized
PK/PD Biomarker Study
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2011-01-26
Enrollment: 84
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Fold Change From Baseline in Fecal Calprotectin at Week 14
timeFrame: Baseline, Week 14
Secondary outcomes:
measure: Maximum Observed Plasma Concentration (Cmax) for Anrukinzumab
timeFrame: Pre-dose to end of the dosing interval after Day 1, Week 12
measure: Minimum Observed Plasma Trough Concentration (Cmin) for Anrukinzumab
timeFrame: Pre-dose to end of the dosing interval after Day 1, Week 12
measure: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) for Anrukinzumab
timeFrame: Pre-dose, within 1 hour post-end of infusion on Day 1; Day 2, 4, 7, pre-dose on Week 2
measure: Plasma Decay Half-Life (t1/2) for Anrukinzumab
timeFrame: Within 1 hour post-end of infusion on Week 12; Week 14, 16, 18, 20, 22, 24, 26, 28, 30, 32
measure: Systemic Clearance (CL) for Anrukinzumab
timeFrame: Pre-dose, within 1 hour post-end of infusion on Week 12; Week 14, 16, 18, 20, 22, 24, 26, 28, 30, 32
measure: Volume of Distribution (Vz) for Anrukinzumab
timeFrame: Pre-dose, within 1 hour post-end of infusion on Week 12; Week 14, 16, 18, 20, 22, 24, 26, 28, 30, 32
measure: Fold Change From Baseline in Fecal Calprotectin at Week 2, 4, 8 and 12
timeFrame: Baseline, Week 2, 4, 8, 12
measure: Total Interleukin-13 (IL-13) Level
timeFrame: Baseline, Day 2, 4, 7, Week 2, 4, 8, 12, 14, 16, 20, 24, 28, 32
measure: Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Baseline up to Week 32
measure: Number of Participants Who Discontinued From the Study Due to Adverse Events
timeFrame: Baseline up to Week 32
measure: Number of Participants With Anti-drug Antibody (ADA) and Neutralizing Antibody
timeFrame: Day 1, Week 4, 8, 12, 14, 16, 20, 24, 28, 32
measure: Number of Participants With Change From Baseline in Endoscopic Subscore at Week 14
timeFrame: Baseline, Week 14
Other outcomes:
measure: Clinical Response Rate at Week 14
timeFrame: Week 14
measure: Clinical Remission Rate at Week 14
timeFrame: Week 14
measure: Change From Baseline in Total Mayo Score at Week 14
timeFrame: Baseline, Week 14
measure: Number of Participants With Change From Baseline in Stool Frequency at Week 14
timeFrame: Baseline, Week 14
measure: Number of Participants With Change From Baseline in Rectal Bleeding at Week 14
timeFrame: Baseline, Week 14
Locations:
city: Birmingham
country: United States
facility: The Kirkland Clinic
state: Alabama
city: Birmingham
country: United States
facility: UAB Hospital
state: Alabama
city: Birmingham
country: United States
facility: UAB Hospital Department of Pharmacy
state: Alabama
city: Birmingham
country: United States
facility: Administrative Offices
state: Alabama
city: Birmingham
country: United States
facility: UAB ACIP
state: Alabama
city: Phoenix
country: United States
facility: Arizona Surgical Center
state: Arizona
city: Phoenix
country: United States
facility: Dedicated Phase I, Inc.
state: Arizona
city: Anaheim
country: United States
facility: AGMG Endoscopy Center
state: California
city: Anaheim
country: United States
facility: Anaheim Clinical Trials, LLC
state: California
city: Santa Ana
country: United States
facility: West Coast Radiology Center
state: California
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: Sanford
country: United States
facility: International Clinical Research - US, LLC
state: Florida
city: Marietta
country: United States
facility: Gastrointestinal Specialists of Georgia, PC
state: Georgia
city: Marietta
country: United States
facility: GI Diagnostics
state: Georgia
city: Jackson
country: United States
facility: Gastrointestinal Associates, PA
state: Mississippi
city: Jackson
country: United States
facility: Gastrointestional Associates, PA
state: Mississippi
city: Jackson
country: United States
facility: St. Dominic Hospital
state: Mississippi
city: Tupelo
country: United States
facility: Digestive Health Specialists, PA
state: Mississippi
city: Tupelo
country: United States
facility: North Mississippi Medical Center
state: Mississippi
city: Poughkeepsie
country: United States
facility: Premier Medical Group of the Hudson Valley
state: New York
city: Winston-Salem
country: United States
facility: Piedmont Gastroenterology Specialists
state: North Carolina
city: Winston-Salem
country: United States
facility: PMG Research of Winston-Salem
state: North Carolina
city: Cleveland
country: United States
facility: University Hospitals Case Medical Center - Division of Gastroenterology and Liver Disease
state: Ohio
city: Oklahoma City
country: United States
facility: Wheeler and Stuckey, Inc.
state: Oklahoma
city: Oklahoma City
country: United States
facility: Oklahoma Foundation for Digestive Research
state: Oklahoma
city: Oklahoma City
country: United States
facility: OU Physicians Building
state: Oklahoma
city: Germantown
country: United States
facility: Memphis Gastroenterology Group, PC
state: Tennessee
city: Memphis
country: United States
facility: The West Clinic
state: Tennessee
city: Nashville
country: United States
facility: Centennial Medical Center Physicians Park
state: Tennessee
city: Nashville
country: United States
facility: Centennial Medical Center Tower Medical Imaging
state: Tennessee
city: Nashville
country: United States
facility: Columbia Medical Group - The First Clinic Inc.
state: Tennessee
city: Nashville
country: United States
facility: Radiology Alliance
state: Tennessee
city: Austin
country: United States
facility: Professional Quality Research, Inc.
state: Texas
city: Austin
country: United States
facility: Austin Endoscopy Center
state: Texas
city: Austin
country: United States
facility: Austin Gastroenterology, PA
state: Texas
city: Houston
country: United States
facility: Texas Center for Drug Development, Inc.
state: Texas
city: Round Rocks
country: United States
facility: Austin Gastroenterology, PA
state: Texas
city: San Antonio
country: United States
facility: Cardiology Clinic of San Antonio
state: Texas
city: San Antonio
country: United States
facility: Gastroenterology Research of San Antonio
state: Texas
city: San Antonio
country: United States
facility: San Antonio Endoscopy Center
state: Texas
city: Murray
country: United States
facility: CNS Pharmacy
state: Utah
city: Salt Lake City
country: United States
facility: RGL Medical Services
state: Utah
city: Salt Lake City
country: United States
facility: Alpine Medical Group
state: Utah
city: Salt Lake City
country: United States
facility: Wasatch Clinical Research
state: Utah
city: Salt Lake City
country: United States
facility: Wasatch Endoscopy Center
state: Utah
city: Salt Lake City
country: United States
facility: University of Utah Hospital
state: Utah
city: Linz
country: Austria
facility: Krankenhaus der Elisabethinen Linz GmbH
city: St. Poelten
country: Austria
facility: Landesklinikum St. Poelten
city: Wien
country: Austria
facility: AKH Wien Universitaetsklinik fuer Innere Medizin III
city: Ruse
country: Bulgaria
facility: MBAL Ruse / MHAT Ruse, Terapevtichno, gastroenterologichno i hematologichno otdelenie
city: Sofia
country: Bulgaria
facility: MBAL Voennomeditsinska Akademia / MMA HAT, Klinika po gastroenterologia i hepatologia
city: Sofia
country: Bulgaria
facility: DKTs Sveta Anna, Gastroenterologichen cabinet
city: Calgary
country: Canada
facility: Heritage Medical Research Clinic - University of Calgary
state: Alberta
city: Vancouver
country: Canada
facility: Vancouver Coastal Health - Vancouver General Hospital
state: British Columbia
city: Vancouver
country: Canada
facility: Vancouver General Hospital - The Gordon and Leslie Diamond Centre
state: British Columbia
city: Kingston
country: Canada
facility: The Religious Hospitallers of St. Joseph of the Hotel Dieu of Kingston
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre
state: Ontario
city: Amiens Cedex 01
country: France
facility: CHU Hopital Nord
city: Clichy
country: France
facility: Hopital Beaujon
city: Nantes CEDEX 1
country: France
facility: CHU Hotel-Dieu
city: Berlin
country: Germany
facility: Charite - Campus Berlin Mitte
city: Heidelberg
country: Germany
facility: Universitaetsklinikum Heidelberg
city: Kiel
country: Germany
facility: Universitaetsklinikum Schleswig-Holstein, Campus Kiel
city: Minden
country: Germany
facility: Gastroenterologische Gemeinschaftspraxis Minden
city: Budapest
country: Hungary
facility: Szent Janos Korhaz es Eszak-budai Egyesitett Korhazak/I. Belgyogyaszati-Gasztroenterologiai Osztaly
city: Budapest
country: Hungary
facility: Pannonia Maganorvosi Centrum Kft.
city: Szekszard
country: Hungary
facility: Clinfan Kft.
city: Amsterdam
country: Netherlands
facility: VU Medisch Centrum
city: Amsterdam
country: Netherlands
facility: Academic Medical Center - University of Amsterdam, Dept. of Gastroenterology
city: Maastricht
country: Netherlands
facility: Academisch Ziekenhuis Maastricht
city: Warszawa
country: Poland
facility: Centralny Szpital Kliniczny MSWiA, Klinika Chorob Wewnetrznych i Gastroenterologii
city: Bucuresti
country: Romania
facility: Sectia Clinica Medicina Interna II
city: Barcelona
country: Spain
facility: Hospital Clinic I Provincial de Barcelona
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañon
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: 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.