Pharmacokinetics/Pharmacodynamics Biomarker Study in Active Ulcerative Colitis Patients
10 november 2014 bijgewerkt door: Pfizer
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.
Studie Overzicht
Toestand
Voltooid
Conditie
Interventie / Behandeling
Studietype
Ingrijpend
Inschrijving (Werkelijk)
84
Fase
- Fase 2
Contacten en locaties
In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.
Studie Locaties
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Ruse, Bulgarije, 7002
- MBAL Ruse / MHAT Ruse, Terapevtichno, gastroenterologichno i hematologichno otdelenie
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Sofia, Bulgarije, 1606
- MBAL Voennomeditsinska Akademia / MMA HAT, Klinika po gastroenterologia i hepatologia
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Sofia, Bulgarije, 1750
- DKTs Sveta Anna, Gastroenterologichen cabinet
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Alberta
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Calgary, Alberta, Canada, T2N 4Z6
- Heritage Medical Research Clinic - University Of Calgary
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British Columbia
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Vancouver, British Columbia, Canada, V5Z 1M9
- Vancouver Coastal Health - Vancouver General Hospital
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Vancouver, British Columbia, Canada, V5Z 1M9
- Vancouver General Hospital - The Gordon and Leslie Diamond Centre
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Ontario
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Kingston, Ontario, Canada, K7L 5G2
- The Religious Hospitallers of St. Joseph of the Hotel Dieu of Kingston
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Toronto, Ontario, Canada, M4N 3M5
- Sunnybrook Health Sciences Centre
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Berlin, Duitsland, 10117
- Charite - Campus Berlin Mitte
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Heidelberg, Duitsland, 69120
- Universitaetsklinikum Heidelberg
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Kiel, Duitsland, 24105
- Universitaetsklinikum Schleswig-Holstein, Campus Kiel
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Minden, Duitsland, 32423
- Gastroenterologische Gemeinschaftspraxis Minden
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Amiens Cedex 01, Frankrijk, 80054
- CHU Hopital Nord
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Clichy, Frankrijk, 92110
- Hopital Beaujon
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Nantes CEDEX 1, Frankrijk, 44093
- CHU Hotel-Dieu
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Budapest, Hongarije, 1136
- Pannonia Maganorvosi Centrum Kft.
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Budapest, Hongarije, 1125
- Szent Janos Korhaz es Eszak-budai Egyesitett Korhazak/I. Belgyogyaszati-Gasztroenterologiai Osztaly
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Szekszard, Hongarije, 7100
- Clinfan Kft.
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Amsterdam, Nederland, 1081 HV
- VU Medisch Centrum
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Amsterdam, Nederland, 1105 AZ
- Academic Medical Center - University of Amsterdam, Dept. of Gastroenterology
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Maastricht, Nederland, 6229 HX
- Academisch Ziekenhuis Maastricht
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Linz, Oostenrijk, 4020
- Krankenhaus Der Elisabethinen Linz Gmbh
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St. Poelten, Oostenrijk, 3100
- Landesklinikum St. Poelten
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Wien, Oostenrijk, 1090
- AKH Wien Universitaetsklinik fuer Innere Medizin III
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Warszawa, Polen, 02-507
- Centralny Szpital Kliniczny MSWiA, Klinika Chorob Wewnetrznych i Gastroenterologii
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Bucuresti, Roemenië, 010816
- Sectia Clinica Medicina Interna II
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Barcelona, Spanje, 08036
- Hospital Clinic i Provincial de Barcelona
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Madrid, Spanje, 28007
- Hospital General Universitario Gregorio Marañón
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Alabama
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Birmingham, Alabama, Verenigde Staten, 35249
- UAB Hospital Department of Pharmacy
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Birmingham, Alabama, Verenigde Staten, 35233
- UAB Hospital
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Birmingham, Alabama, Verenigde Staten, 35233
- The Kirkland Clinic
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Birmingham, Alabama, Verenigde Staten, 35294
- Administrative Offices
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Birmingham, Alabama, Verenigde Staten, 35294
- UAB ACIP
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Arizona
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Phoenix, Arizona, Verenigde Staten, 85013
- Dedicated Phase I, Inc.
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Phoenix, Arizona, Verenigde Staten, 85006
- Arizona Surgical Center
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California
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Anaheim, California, Verenigde Staten, 92801
- Anaheim Clinical Trials, LLC
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Anaheim, California, Verenigde Staten, 92801
- AGMG Endoscopy Center
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Santa Ana, California, Verenigde Staten, 92705
- West Coast Radiology Center
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Connecticut
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Hamden, Connecticut, Verenigde Staten, 06518
- Medical Research Center of Connecticut, LLC
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Hamden, Connecticut, Verenigde Staten, 06518
- Gastroenterology Center of Connecticut, PC
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Hamden, Connecticut, Verenigde Staten, 06518
- Endoscopy Center of Connecticut, LLC
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Florida
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Sanford, Florida, Verenigde Staten, 32771
- International Clinical Research - US, LLC
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Georgia
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Marietta, Georgia, Verenigde Staten, 30060
- Gastrointestinal Specialists of Georgia, PC
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Marietta, Georgia, Verenigde Staten, 30067
- GI Diagnostics
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Mississippi
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Jackson, Mississippi, Verenigde Staten, 39216
- St. Dominic Hospital
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Jackson, Mississippi, Verenigde Staten, 39202
- Gastrointestinal Associates, PA
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Jackson, Mississippi, Verenigde Staten, 39202
- Gastrointestional Associates, PA
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Tupelo, Mississippi, Verenigde Staten, 38801
- North Mississippi Medical Center
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Tupelo, Mississippi, Verenigde Staten, 38801
- Digestive Health Specialists, PA
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New York
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Poughkeepsie, New York, Verenigde Staten, 12601
- Premier Medical Group of the Hudson Valley
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North Carolina
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Winston-Salem, North Carolina, Verenigde Staten, 27103
- PMG Research of Winston-Salem
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Winston-Salem, North Carolina, Verenigde Staten, 27103
- Piedmont Gastroenterology Specialists
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Ohio
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Cleveland, Ohio, Verenigde Staten, 44106
- University Hospitals Case Medical Center - Division of Gastroenterology and Liver Disease
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Oklahoma
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Oklahoma City, Oklahoma, Verenigde Staten, 73104
- Oklahoma Foundation for Digestive Research
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Oklahoma City, Oklahoma, Verenigde Staten, 73104
- OU Physicians Building
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Oklahoma City, Oklahoma, Verenigde Staten, 73103
- Wheeler and Stuckey, Inc.
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Tennessee
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Germantown, Tennessee, Verenigde Staten, 38138
- Memphis Gastroenterology Group, PC
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Memphis, Tennessee, Verenigde Staten, 38120
- The West Clinic
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Nashville, Tennessee, Verenigde Staten, 37203
- Centennial Medical Center Physicians Park
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Nashville, Tennessee, Verenigde Staten, 37203
- Centennial Medical Center Tower Medical Imaging
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Nashville, Tennessee, Verenigde Staten, 37203
- Columbia Medical Group - The First Clinic Inc.
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Nashville, Tennessee, Verenigde Staten, 37203
- Radiology Alliance
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Texas
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Austin, Texas, Verenigde Staten, 78705
- Professional Quality Research, Inc.
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Austin, Texas, Verenigde Staten, 78757
- Austin Endoscopy Center
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Austin, Texas, Verenigde Staten, 78757
- Austin Gastroenterology, PA
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Houston, Texas, Verenigde Staten, 77081
- Texas Center for Drug Development, Inc.
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Round Rocks, Texas, Verenigde Staten, 78681
- Austin Gastroenterology, PA
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San Antonio, Texas, Verenigde Staten, 78229
- Cardiology Clinic of San Antonio
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San Antonio, Texas, Verenigde Staten, 78229
- Gastroenterology Research of San Antonio
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San Antonio, Texas, Verenigde Staten, 78229
- San Antonio Endoscopy Center
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Utah
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Murray, Utah, Verenigde Staten, 84123
- CNS Pharmacy
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Salt Lake City, Utah, Verenigde Staten, 84132
- University of Utah Hospital
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Salt Lake City, Utah, Verenigde Staten, 84102
- Alpine Medical Group
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Salt Lake City, Utah, Verenigde Staten, 84107
- Wasatch Clinical Research
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Salt Lake City, Utah, Verenigde Staten, 84124
- Wasatch Endoscopy Center
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Salt Lake City, Utah, Verenigde Staten, 84084
- RGL Medical Services
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Deelname Criteria
Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.
Geschiktheidscriteria
Leeftijden die in aanmerking komen voor studie
18 jaar tot 65 jaar (Volwassen, Oudere volwassene)
Accepteert gezonde vrijwilligers
Nee
Geslachten die in aanmerking komen voor studie
Allemaal
Beschrijving
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.
Studie plan
Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.
Hoe is de studie opgezet?
Ontwerpdetails
- Primair doel: Behandeling
- Toewijzing: Gerandomiseerd
- Interventioneel model: Parallelle opdracht
- Masker: Verdrievoudigen
Wapens en interventies
Deelnemersgroep / Arm |
Interventie / Behandeling |
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Experimenteel: Arm 1
200 mg PF-05230917, Anrukinzumab active dose level
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200 mg sterile liquid vial, administered intravenously, one-hour infusion on Day 1, Week 2, 4, 8, and 12
Andere namen:
200 mg sterile liquid vial, dose level 400 mg administered intravenously, one-hour infusion on Day 1, Week 2, 4, 8, and 12
Andere namen:
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.
Andere namen:
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Experimenteel: Arm 2
400 mg PF-05230917, Anrukinzumab active dose level
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200 mg sterile liquid vial, administered intravenously, one-hour infusion on Day 1, Week 2, 4, 8, and 12
Andere namen:
200 mg sterile liquid vial, dose level 400 mg administered intravenously, one-hour infusion on Day 1, Week 2, 4, 8, and 12
Andere namen:
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.
Andere namen:
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Experimenteel: Arm 3
600 mg PF-05230917, Anrukinzumab active dose level
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200 mg sterile liquid vial, administered intravenously, one-hour infusion on Day 1, Week 2, 4, 8, and 12
Andere namen:
200 mg sterile liquid vial, dose level 400 mg administered intravenously, one-hour infusion on Day 1, Week 2, 4, 8, and 12
Andere namen:
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.
Andere namen:
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Placebo-vergelijker: Arm 4
Matching placebo - administered at matching dose level 200 mg, 400 mg or 600 mg.
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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
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Wat meet het onderzoek?
Primaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
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Fold Change From Baseline in Fecal Calprotectin at Week 14
Tijdsspanne: Baseline, Week 14
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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.
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Baseline, Week 14
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Secundaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
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Maximum Observed Plasma Concentration (Cmax) for Anrukinzumab
Tijdsspanne: Pre-dose to end of the dosing interval after Day 1, Week 12
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Maximum concentration observed during the dosing interval (2 weeks for day 1, 4 weeks for week 12).
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Pre-dose to end of the dosing interval after Day 1, Week 12
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Minimum Observed Plasma Trough Concentration (Cmin) for Anrukinzumab
Tijdsspanne: Pre-dose to end of the dosing interval after Day 1, Week 12
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Lowest concentration observed during the dosing interval (2 weeks for day 1, 4 weeks for week 12).
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Pre-dose to end of the dosing interval after Day 1, Week 12
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Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) for Anrukinzumab
Tijdsspanne: Pre-dose, within 1 hour post-end of infusion on Day 1; Day 2, 4, 7, pre-dose on Week 2
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Area under the plasma concentration curve from time zero to end of dosing interval (2 weeks) was reported.
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Pre-dose, within 1 hour post-end of infusion on Day 1; Day 2, 4, 7, pre-dose on Week 2
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Plasma Decay Half-Life (t1/2) for Anrukinzumab
Tijdsspanne: Within 1 hour post-end of infusion on Week 12; Week 14, 16, 18, 20, 22, 24, 26, 28, 30, 32
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Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
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Within 1 hour post-end of infusion on Week 12; Week 14, 16, 18, 20, 22, 24, 26, 28, 30, 32
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Systemic Clearance (CL) for Anrukinzumab
Tijdsspanne: Pre-dose, within 1 hour post-end of infusion on Week 12; Week 14, 16, 18, 20, 22, 24, 26, 28, 30, 32
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CL is a quantitative measure of the rate at which a drug substance is removed from the body.
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Pre-dose, within 1 hour post-end of infusion on Week 12; Week 14, 16, 18, 20, 22, 24, 26, 28, 30, 32
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Volume of Distribution (Vz) for Anrukinzumab
Tijdsspanne: Pre-dose, within 1 hour post-end of infusion on Week 12; Week 14, 16, 18, 20, 22, 24, 26, 28, 30, 32
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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.
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Pre-dose, within 1 hour post-end of infusion on Week 12; Week 14, 16, 18, 20, 22, 24, 26, 28, 30, 32
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Fold Change From Baseline in Fecal Calprotectin at Week 2, 4, 8 and 12
Tijdsspanne: Baseline, Week 2, 4, 8, 12
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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.
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Baseline, Week 2, 4, 8, 12
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Total Interleukin-13 (IL-13) Level
Tijdsspanne: Baseline, Day 2, 4, 7, Week 2, 4, 8, 12, 14, 16, 20, 24, 28, 32
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Baseline, Day 2, 4, 7, Week 2, 4, 8, 12, 14, 16, 20, 24, 28, 32
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Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Tijdsspanne: Baseline up to Week 32
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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.
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Baseline up to Week 32
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Number of Participants Who Discontinued From the Study Due to Adverse Events
Tijdsspanne: Baseline up to Week 32
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Baseline up to Week 32
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Number of Participants With Anti-drug Antibody (ADA) and Neutralizing Antibody
Tijdsspanne: Day 1, Week 4, 8, 12, 14, 16, 20, 24, 28, 32
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Neutralizing antibody was not analyzed as no participant had positive ADA samples.
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Day 1, Week 4, 8, 12, 14, 16, 20, 24, 28, 32
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Number of Participants With Change From Baseline in Endoscopic Subscore at Week 14
Tijdsspanne: Baseline, Week 14
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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.
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Baseline, Week 14
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Andere uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
|---|---|---|
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Clinical Response Rate at Week 14
Tijdsspanne: Week 14
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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.
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Week 14
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Clinical Remission Rate at Week 14
Tijdsspanne: Week 14
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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.
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Week 14
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Change From Baseline in Total Mayo Score at Week 14
Tijdsspanne: Baseline, Week 14
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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.
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Baseline, Week 14
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Number of Participants With Change From Baseline in Stool Frequency at Week 14
Tijdsspanne: Baseline, Week 14
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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.
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Baseline, Week 14
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Number of Participants With Change From Baseline in Rectal Bleeding at Week 14
Tijdsspanne: Baseline, Week 14
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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.
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Baseline, Week 14
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Medewerkers en onderzoekers
Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.
Sponsor
Publicaties en nuttige links
De persoon die verantwoordelijk is voor het invoeren van informatie over het onderzoek stelt deze publicaties vrijwillig ter beschikking. Dit kan gaan over alles wat met het onderzoek te maken heeft.
Studie record data
Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.
Bestudeer belangrijke data
Studie start
1 maart 2011
Primaire voltooiing (Werkelijk)
1 april 2013
Studie voltooiing (Werkelijk)
1 april 2013
Studieregistratiedata
Eerst ingediend
25 januari 2011
Eerst ingediend dat voldeed aan de QC-criteria
25 januari 2011
Eerst geplaatst (Schatting)
26 januari 2011
Updates van studierecords
Laatste update geplaatst (Schatting)
18 november 2014
Laatste update ingediend die voldeed aan QC-criteria
10 november 2014
Laatst geverifieerd
1 november 2014
Meer informatie
Termen gerelateerd aan deze studie
Aanvullende relevante MeSH-voorwaarden
Andere studie-ID-nummers
- B2421003
- IMA-638 Anti-IL13 mAb
- 2010-023762-49 (EudraCT-nummer)
Deze informatie is zonder wijzigingen rechtstreeks van de website clinicaltrials.gov gehaald. Als u verzoeken heeft om uw onderzoeksgegevens te wijzigen, te verwijderen of bij te werken, neem dan contact op met register@clinicaltrials.gov. Zodra er een wijziging wordt doorgevoerd op clinicaltrials.gov, wordt deze ook automatisch bijgewerkt op onze website .