Pharmacokinetics/Pharmacodynamics Biomarker Study in Active Ulcerative Colitis Patients

Colitis, Ulcerative Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01284062
• Other study ID #: B2421003
• Secondary ID: IMA-638 Anti-IL1
• Status: Completed
• Phase: Phase 2
• First received: January 25, 2011
• Last updated: November 10, 2014
• Start date: March 2011
• Est. completion date: April 2013

Study information

• Verified date: November 2014
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 84
• Est. completion date: April 2013
• Est. primary completion date: April 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Colitis
• Colitis, Ulcerative
• Ulcer

Intervention

Biological:
• Anrukinzumab
200 mg sterile liquid vial, administered intravenously, one-hour infusion on Day 1, Week 2, 4, 8, and 12
• Anrukinzumab
200 mg sterile liquid vial, dose level 400 mg administered intravenously, one-hour infusion on Day 1, Week 2, 4, 8, and 12
• 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:
• 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

Locations

Country	Name	City	State
Austria	Krankenhaus der Elisabethinen Linz GmbH	Linz
Austria	Landesklinikum St. Poelten	St. Poelten
Austria	AKH Wien Universitaetsklinik fuer Innere Medizin III	Wien
Bulgaria	MBAL Ruse / MHAT Ruse, Terapevtichno, gastroenterologichno i hematologichno otdelenie	Ruse
Bulgaria	DKTs Sveta Anna, Gastroenterologichen cabinet	Sofia
Bulgaria	MBAL Voennomeditsinska Akademia / MMA HAT, Klinika po gastroenterologia i hepatologia	Sofia
Canada	Heritage Medical Research Clinic - University of Calgary	Calgary	Alberta
Canada	The Religious Hospitallers of St. Joseph of the Hotel Dieu of Kingston	Kingston	Ontario
Canada	Sunnybrook Health Sciences Centre	Toronto	Ontario
Canada	Vancouver Coastal Health - Vancouver General Hospital	Vancouver	British Columbia
Canada	Vancouver General Hospital - The Gordon and Leslie Diamond Centre	Vancouver	British Columbia
France	CHU Hopital Nord	Amiens Cedex 01
France	Hopital Beaujon	Clichy
France	CHU Hotel-Dieu	Nantes CEDEX 1
Germany	Charite - Campus Berlin Mitte	Berlin
Germany	Universitaetsklinikum Heidelberg	Heidelberg
Germany	Universitaetsklinikum Schleswig-Holstein, Campus Kiel	Kiel
Germany	Gastroenterologische Gemeinschaftspraxis Minden	Minden
Hungary	Pannonia Maganorvosi Centrum Kft.	Budapest
Hungary	Szent Janos Korhaz es Eszak-budai Egyesitett Korhazak/I. Belgyogyaszati-Gasztroenterologiai Osztaly	Budapest
Hungary	Clinfan Kft.	Szekszard
Netherlands	Academic Medical Center - University of Amsterdam, Dept. of Gastroenterology	Amsterdam
Netherlands	VU Medisch Centrum	Amsterdam
Netherlands	Academisch Ziekenhuis Maastricht	Maastricht
Poland	Centralny Szpital Kliniczny MSWiA, Klinika Chorob Wewnetrznych i Gastroenterologii	Warszawa
Romania	Sectia Clinica Medicina Interna II	Bucuresti
Spain	Hospital Clinic I Provincial de Barcelona	Barcelona
Spain	Hospital General Universitario Gregorio Marañon	Madrid
United States	AGMG Endoscopy Center	Anaheim	California
United States	Anaheim Clinical Trials, LLC	Anaheim	California
United States	Austin Endoscopy Center	Austin	Texas
United States	Austin Gastroenterology, PA	Austin	Texas
United States	Professional Quality Research, Inc.	Austin	Texas
United States	Administrative Offices	Birmingham	Alabama
United States	The Kirkland Clinic	Birmingham	Alabama
United States	UAB ACIP	Birmingham	Alabama
United States	UAB Hospital	Birmingham	Alabama
United States	UAB Hospital Department of Pharmacy	Birmingham	Alabama
United States	University Hospitals Case Medical Center - Division of Gastroenterology and Liver Disease	Cleveland	Ohio
United States	Memphis Gastroenterology Group, PC	Germantown	Tennessee
United States	Endoscopy Center of Connecticut, LLC	Hamden	Connecticut
United States	Gastroenterology Center of Connecticut, PC	Hamden	Connecticut
United States	Medical Research Center of Connecticut, LLC	Hamden	Connecticut
United States	Texas Center for Drug Development, Inc.	Houston	Texas
United States	Gastrointestinal Associates, PA	Jackson	Mississippi
United States	Gastrointestional Associates, PA	Jackson	Mississippi
United States	St. Dominic Hospital	Jackson	Mississippi
United States	Gastrointestinal Specialists of Georgia, PC	Marietta	Georgia
United States	GI Diagnostics	Marietta	Georgia
United States	The West Clinic	Memphis	Tennessee
United States	CNS Pharmacy	Murray	Utah
United States	Centennial Medical Center Physicians Park	Nashville	Tennessee
United States	Centennial Medical Center Tower Medical Imaging	Nashville	Tennessee
United States	Columbia Medical Group - The First Clinic Inc.	Nashville	Tennessee
United States	Radiology Alliance	Nashville	Tennessee
United States	Oklahoma Foundation for Digestive Research	Oklahoma City	Oklahoma
United States	OU Physicians Building	Oklahoma City	Oklahoma
United States	Wheeler and Stuckey, Inc.	Oklahoma City	Oklahoma
United States	Arizona Surgical Center	Phoenix	Arizona
United States	Dedicated Phase I, Inc.	Phoenix	Arizona
United States	Premier Medical Group of the Hudson Valley	Poughkeepsie	New York
United States	Austin Gastroenterology, PA	Round Rocks	Texas
United States	Alpine Medical Group	Salt Lake City	Utah
United States	RGL Medical Services	Salt Lake City	Utah
United States	University of Utah Hospital	Salt Lake City	Utah
United States	Wasatch Clinical Research	Salt Lake City	Utah
United States	Wasatch Endoscopy Center	Salt Lake City	Utah
United States	Cardiology Clinic of San Antonio	San Antonio	Texas
United States	Gastroenterology Research of San Antonio	San Antonio	Texas
United States	San Antonio Endoscopy Center	San Antonio	Texas
United States	International Clinical Research - US, LLC	Sanford	Florida
United States	West Coast Radiology Center	Santa Ana	California
United States	Digestive Health Specialists, PA	Tupelo	Mississippi
United States	North Mississippi Medical Center	Tupelo	Mississippi
United States	Piedmont Gastroenterology Specialists	Winston-Salem	North Carolina
United States	PMG Research of Winston-Salem	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Countries where clinical trial is conducted

United States,  Austria,  Bulgaria,  Canada,  France,  Germany,  Hungary,  Netherlands,  Poland,  Romania,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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	No
Other	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	No
Other	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	No
Other	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	No
Other	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	No
Primary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	Total Interleukin-13 (IL-13) Level		Baseline, Day 2, 4, 7, Week 2, 4, 8, 12, 14, 16, 20, 24, 28, 32	No
Secondary	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	Yes
Secondary	Number of Participants Who Discontinued From the Study Due to Adverse Events		Baseline up to Week 32	Yes
Secondary	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	Yes
Secondary	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	No

External Links

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