Pharmacokinetics/Pharmacodynamics Biomarker Study in Active Ulcerative Colitis Patients
10 novembre 2014 aggiornato da: 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.
Panoramica dello studio
Stato
Completato
Condizioni
Intervento / Trattamento
Tipo di studio
Interventistico
Iscrizione (Effettivo)
84
Fase
- Fase 2
Contatti e Sedi
Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.
Luoghi di studio
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Linz, Austria, 4020
- Krankenhaus der Elisabethinen Linz GmbH
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St. Poelten, Austria, 3100
- Landesklinikum St. Poelten
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Wien, Austria, 1090
- AKH Wien Universitaetsklinik fuer Innere Medizin III
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Ruse, Bulgaria, 7002
- MBAL Ruse / MHAT Ruse, Terapevtichno, gastroenterologichno i hematologichno otdelenie
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Sofia, Bulgaria, 1606
- MBAL Voennomeditsinska Akademia / MMA HAT, Klinika po gastroenterologia i hepatologia
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Sofia, Bulgaria, 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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Amiens Cedex 01, Francia, 80054
- CHU Hopital Nord
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Clichy, Francia, 92110
- Hôpital Beaujon
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Nantes CEDEX 1, Francia, 44093
- CHU Hotel-Dieu
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Berlin, Germania, 10117
- Charite - Campus Berlin Mitte
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Heidelberg, Germania, 69120
- Universitaetsklinikum Heidelberg
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Kiel, Germania, 24105
- Universitaetsklinikum Schleswig-Holstein, Campus Kiel
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Minden, Germania, 32423
- Gastroenterologische Gemeinschaftspraxis Minden
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Amsterdam, Olanda, 1081 HV
- VU Medisch Centrum
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Amsterdam, Olanda, 1105 AZ
- Academic Medical Center - University of Amsterdam, Dept. of Gastroenterology
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Maastricht, Olanda, 6229 HX
- Academisch Ziekenhuis Maastricht
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Warszawa, Polonia, 02-507
- Centralny Szpital Kliniczny MSWiA, Klinika Chorob Wewnetrznych i Gastroenterologii
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Bucuresti, Romania, 010816
- Sectia Clinica Medicina Interna II
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Barcelona, Spagna, 08036
- Hospital Clinic i Provincial de Barcelona
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Madrid, Spagna, 28007
- Hospital General Universitario Gregorio Marañón
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Alabama
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Birmingham, Alabama, Stati Uniti, 35249
- UAB Hospital Department of Pharmacy
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Birmingham, Alabama, Stati Uniti, 35233
- UAB Hospital
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Birmingham, Alabama, Stati Uniti, 35233
- The Kirkland Clinic
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Birmingham, Alabama, Stati Uniti, 35294
- Administrative Offices
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Birmingham, Alabama, Stati Uniti, 35294
- UAB ACIP
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Arizona
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Phoenix, Arizona, Stati Uniti, 85013
- Dedicated Phase I, Inc.
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Phoenix, Arizona, Stati Uniti, 85006
- Arizona Surgical Center
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California
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Anaheim, California, Stati Uniti, 92801
- Anaheim Clinical Trials, LLC
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Anaheim, California, Stati Uniti, 92801
- AGMG Endoscopy Center
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Santa Ana, California, Stati Uniti, 92705
- West Coast Radiology Center
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Connecticut
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Hamden, Connecticut, Stati Uniti, 06518
- Medical Research Center of Connecticut, LLC
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Hamden, Connecticut, Stati Uniti, 06518
- Gastroenterology Center of Connecticut, PC
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Hamden, Connecticut, Stati Uniti, 06518
- Endoscopy Center of Connecticut, LLC
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Florida
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Sanford, Florida, Stati Uniti, 32771
- International Clinical Research - US, LLC
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Georgia
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Marietta, Georgia, Stati Uniti, 30060
- Gastrointestinal Specialists of Georgia, PC
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Marietta, Georgia, Stati Uniti, 30067
- GI Diagnostics
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Mississippi
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Jackson, Mississippi, Stati Uniti, 39216
- St. Dominic Hospital
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Jackson, Mississippi, Stati Uniti, 39202
- Gastrointestinal Associates, PA
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Jackson, Mississippi, Stati Uniti, 39202
- Gastrointestional Associates, PA
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Tupelo, Mississippi, Stati Uniti, 38801
- North Mississippi Medical Center
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Tupelo, Mississippi, Stati Uniti, 38801
- Digestive Health Specialists, PA
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New York
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Poughkeepsie, New York, Stati Uniti, 12601
- Premier Medical Group of the Hudson Valley
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North Carolina
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Winston-Salem, North Carolina, Stati Uniti, 27103
- PMG Research of Winston-Salem
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Winston-Salem, North Carolina, Stati Uniti, 27103
- Piedmont Gastroenterology Specialists
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Ohio
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Cleveland, Ohio, Stati Uniti, 44106
- University Hospitals Case Medical Center - Division of Gastroenterology and Liver Disease
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Oklahoma
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Oklahoma City, Oklahoma, Stati Uniti, 73104
- Oklahoma Foundation for Digestive Research
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Oklahoma City, Oklahoma, Stati Uniti, 73104
- OU Physicians Building
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Oklahoma City, Oklahoma, Stati Uniti, 73103
- Wheeler and Stuckey, Inc.
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Tennessee
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Germantown, Tennessee, Stati Uniti, 38138
- Memphis Gastroenterology Group, PC
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Memphis, Tennessee, Stati Uniti, 38120
- The West Clinic
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Nashville, Tennessee, Stati Uniti, 37203
- Centennial Medical Center Physicians Park
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Nashville, Tennessee, Stati Uniti, 37203
- Centennial Medical Center Tower Medical Imaging
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Nashville, Tennessee, Stati Uniti, 37203
- Columbia Medical Group - The First Clinic Inc.
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Nashville, Tennessee, Stati Uniti, 37203
- Radiology Alliance
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Texas
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Austin, Texas, Stati Uniti, 78705
- Professional Quality Research, Inc.
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Austin, Texas, Stati Uniti, 78757
- Austin Endoscopy Center
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Austin, Texas, Stati Uniti, 78757
- Austin Gastroenterology, PA
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Houston, Texas, Stati Uniti, 77081
- Texas Center for Drug Development, Inc.
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Round Rocks, Texas, Stati Uniti, 78681
- Austin Gastroenterology, PA
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San Antonio, Texas, Stati Uniti, 78229
- Cardiology Clinic of San Antonio
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San Antonio, Texas, Stati Uniti, 78229
- Gastroenterology Research of San Antonio
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San Antonio, Texas, Stati Uniti, 78229
- San Antonio Endoscopy Center
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Utah
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Murray, Utah, Stati Uniti, 84123
- CNS Pharmacy
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Salt Lake City, Utah, Stati Uniti, 84132
- University of Utah Hospital
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Salt Lake City, Utah, Stati Uniti, 84102
- Alpine Medical Group
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Salt Lake City, Utah, Stati Uniti, 84107
- Wasatch Clinical Research
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Salt Lake City, Utah, Stati Uniti, 84124
- Wasatch Endoscopy Center
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Salt Lake City, Utah, Stati Uniti, 84084
- RGL Medical Services
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Budapest, Ungheria, 1136
- Pannonia Maganorvosi Centrum Kft.
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Budapest, Ungheria, 1125
- Szent Janos Korhaz es Eszak-budai Egyesitett Korhazak/I. Belgyogyaszati-Gasztroenterologiai Osztaly
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Szekszard, Ungheria, 7100
- Clinfan Kft.
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Criteri di partecipazione
I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.
Criteri di ammissibilità
Età idonea allo studio
Da 18 anni a 65 anni (Adulto, Adulto più anziano)
Accetta volontari sani
No
Sessi ammissibili allo studio
Tutto
Descrizione
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.
Piano di studio
Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.
Come è strutturato lo studio?
Dettagli di progettazione
- Scopo principale: Trattamento
- Assegnazione: Randomizzato
- Modello interventistico: Assegnazione parallela
- Mascheramento: Triplicare
Armi e interventi
Gruppo di partecipanti / Arm |
Intervento / Trattamento |
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Sperimentale: 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
Altri nomi:
200 mg sterile liquid vial, dose level 400 mg administered intravenously, one-hour infusion on Day 1, Week 2, 4, 8, and 12
Altri nomi:
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.
Altri nomi:
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Sperimentale: 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
Altri nomi:
200 mg sterile liquid vial, dose level 400 mg administered intravenously, one-hour infusion on Day 1, Week 2, 4, 8, and 12
Altri nomi:
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.
Altri nomi:
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Sperimentale: 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
Altri nomi:
200 mg sterile liquid vial, dose level 400 mg administered intravenously, one-hour infusion on Day 1, Week 2, 4, 8, and 12
Altri nomi:
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.
Altri nomi:
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Comparatore placebo: 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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Cosa sta misurando lo studio?
Misure di risultato primarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
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Fold Change From Baseline in Fecal Calprotectin at Week 14
Lasso di tempo: 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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Misure di risultato secondarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
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Maximum Observed Plasma Concentration (Cmax) for Anrukinzumab
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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)
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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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Altre misure di risultato
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
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Clinical Response Rate at Week 14
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: Baseline, 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.
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Baseline, Week 14
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Number of Participants With Change From Baseline in Rectal Bleeding at Week 14
Lasso di tempo: Baseline, 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
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Collaboratori e investigatori
Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.
Sponsor
Pubblicazioni e link utili
La persona responsabile dell'inserimento delle informazioni sullo studio fornisce volontariamente queste pubblicazioni. Questi possono riguardare qualsiasi cosa relativa allo studio.
Collegamenti utili
Studiare le date dei record
Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.
Studia le date principali
Inizio studio
1 marzo 2011
Completamento primario (Effettivo)
1 aprile 2013
Completamento dello studio (Effettivo)
1 aprile 2013
Date di iscrizione allo studio
Primo inviato
25 gennaio 2011
Primo inviato che soddisfa i criteri di controllo qualità
25 gennaio 2011
Primo Inserito (Stima)
26 gennaio 2011
Aggiornamenti dei record di studio
Ultimo aggiornamento pubblicato (Stima)
18 novembre 2014
Ultimo aggiornamento inviato che soddisfa i criteri QC
10 novembre 2014
Ultimo verificato
1 novembre 2014
Maggiori informazioni
Termini relativi a questo studio
Termini MeSH pertinenti aggiuntivi
Altri numeri di identificazione dello studio
- B2421003
- IMA-638 Anti-IL13 mAb
- 2010-023762-49 (Numero EudraCT)
Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .