Pharmacokinetics/Pharmacodynamics Biomarker Study in Active Ulcerative Colitis Patients
10 novembre 2014 mis à jour par: 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.
Aperçu de l'étude
Statut
Complété
Les conditions
Intervention / Traitement
Type d'étude
Interventionnel
Inscription (Réel)
84
Phase
- Phase 2
Contacts et emplacements
Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.
Lieux d'étude
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Berlin, Allemagne, 10117
- Charite - Campus Berlin Mitte
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Heidelberg, Allemagne, 69120
- Universitaetsklinikum Heidelberg
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Kiel, Allemagne, 24105
- Universitaetsklinikum Schleswig-Holstein, Campus Kiel
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Minden, Allemagne, 32423
- Gastroenterologische Gemeinschaftspraxis Minden
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Ruse, Bulgarie, 7002
- MBAL Ruse / MHAT Ruse, Terapevtichno, gastroenterologichno i hematologichno otdelenie
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Sofia, Bulgarie, 1606
- MBAL Voennomeditsinska Akademia / MMA HAT, Klinika po gastroenterologia i hepatologia
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Sofia, Bulgarie, 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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Barcelona, Espagne, 08036
- Hospital Clinic i Provincial de Barcelona
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Madrid, Espagne, 28007
- Hospital General Universitario Gregorio Marañón
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Amiens Cedex 01, France, 80054
- CHU Hopital Nord
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Clichy, France, 92110
- Hopital Beaujon
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Nantes CEDEX 1, France, 44093
- CHU Hotel-Dieu
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Budapest, Hongrie, 1136
- Pannonia Maganorvosi Centrum Kft.
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Budapest, Hongrie, 1125
- Szent Janos Korhaz es Eszak-budai Egyesitett Korhazak/I. Belgyogyaszati-Gasztroenterologiai Osztaly
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Szekszard, Hongrie, 7100
- Clinfan Kft.
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Linz, L'Autriche, 4020
- Krankenhaus Der Elisabethinen Linz Gmbh
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St. Poelten, L'Autriche, 3100
- Landesklinikum St. Poelten
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Wien, L'Autriche, 1090
- AKH Wien Universitaetsklinik fuer Innere Medizin III
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Amsterdam, Pays-Bas, 1081 HV
- VU Medisch Centrum
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Amsterdam, Pays-Bas, 1105 AZ
- Academic Medical Center - University of Amsterdam, Dept. of Gastroenterology
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Maastricht, Pays-Bas, 6229 HX
- Academisch Ziekenhuis Maastricht
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Warszawa, Pologne, 02-507
- Centralny Szpital Kliniczny MSWiA, Klinika Chorob Wewnetrznych i Gastroenterologii
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Bucuresti, Roumanie, 010816
- Sectia Clinica Medicina Interna II
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Alabama
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Birmingham, Alabama, États-Unis, 35249
- UAB Hospital Department of Pharmacy
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Birmingham, Alabama, États-Unis, 35233
- UAB Hospital
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Birmingham, Alabama, États-Unis, 35233
- The Kirkland Clinic
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Birmingham, Alabama, États-Unis, 35294
- Administrative Offices
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Birmingham, Alabama, États-Unis, 35294
- UAB ACIP
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Arizona
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Phoenix, Arizona, États-Unis, 85013
- Dedicated Phase I, Inc.
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Phoenix, Arizona, États-Unis, 85006
- Arizona Surgical Center
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California
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Anaheim, California, États-Unis, 92801
- Anaheim Clinical Trials, LLC
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Anaheim, California, États-Unis, 92801
- AGMG Endoscopy Center
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Santa Ana, California, États-Unis, 92705
- West Coast Radiology Center
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Connecticut
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Hamden, Connecticut, États-Unis, 06518
- Medical Research Center of Connecticut, LLC
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Hamden, Connecticut, États-Unis, 06518
- Gastroenterology Center of Connecticut, PC
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Hamden, Connecticut, États-Unis, 06518
- Endoscopy Center of Connecticut, LLC
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Florida
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Sanford, Florida, États-Unis, 32771
- International Clinical Research - US, LLC
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Georgia
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Marietta, Georgia, États-Unis, 30060
- Gastrointestinal Specialists of Georgia, PC
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Marietta, Georgia, États-Unis, 30067
- GI Diagnostics
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Mississippi
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Jackson, Mississippi, États-Unis, 39216
- St. Dominic Hospital
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Jackson, Mississippi, États-Unis, 39202
- Gastrointestinal Associates, PA
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Jackson, Mississippi, États-Unis, 39202
- Gastrointestional Associates, PA
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Tupelo, Mississippi, États-Unis, 38801
- North Mississippi Medical Center
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Tupelo, Mississippi, États-Unis, 38801
- Digestive Health Specialists, PA
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New York
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Poughkeepsie, New York, États-Unis, 12601
- Premier Medical Group of the Hudson Valley
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North Carolina
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Winston-Salem, North Carolina, États-Unis, 27103
- PMG Research of Winston-Salem
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Winston-Salem, North Carolina, États-Unis, 27103
- Piedmont Gastroenterology Specialists
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Ohio
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Cleveland, Ohio, États-Unis, 44106
- University Hospitals Case Medical Center - Division of Gastroenterology and Liver Disease
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Oklahoma
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Oklahoma City, Oklahoma, États-Unis, 73104
- Oklahoma Foundation for Digestive Research
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Oklahoma City, Oklahoma, États-Unis, 73104
- OU Physicians Building
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Oklahoma City, Oklahoma, États-Unis, 73103
- Wheeler and Stuckey, Inc.
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Tennessee
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Germantown, Tennessee, États-Unis, 38138
- Memphis Gastroenterology Group, PC
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Memphis, Tennessee, États-Unis, 38120
- The West Clinic
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Nashville, Tennessee, États-Unis, 37203
- Centennial Medical Center Physicians Park
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Nashville, Tennessee, États-Unis, 37203
- Centennial Medical Center Tower Medical Imaging
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Nashville, Tennessee, États-Unis, 37203
- Columbia Medical Group - The First Clinic Inc.
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Nashville, Tennessee, États-Unis, 37203
- Radiology Alliance
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Texas
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Austin, Texas, États-Unis, 78705
- Professional Quality Research, Inc.
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Austin, Texas, États-Unis, 78757
- Austin Endoscopy Center
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Austin, Texas, États-Unis, 78757
- Austin Gastroenterology, PA
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Houston, Texas, États-Unis, 77081
- Texas Center for Drug Development, Inc.
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Round Rocks, Texas, États-Unis, 78681
- Austin Gastroenterology, PA
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San Antonio, Texas, États-Unis, 78229
- Cardiology Clinic of San Antonio
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San Antonio, Texas, États-Unis, 78229
- Gastroenterology Research of San Antonio
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San Antonio, Texas, États-Unis, 78229
- San Antonio Endoscopy Center
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Utah
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Murray, Utah, États-Unis, 84123
- CNS Pharmacy
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Salt Lake City, Utah, États-Unis, 84132
- University of Utah Hospital
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Salt Lake City, Utah, États-Unis, 84102
- Alpine Medical Group
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Salt Lake City, Utah, États-Unis, 84107
- Wasatch Clinical Research
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Salt Lake City, Utah, États-Unis, 84124
- Wasatch Endoscopy Center
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Salt Lake City, Utah, États-Unis, 84084
- RGL Medical Services
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Critères de participation
Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.
Critère d'éligibilité
Âges éligibles pour étudier
18 ans à 65 ans (Adulte, Adulte plus âgé)
Accepte les volontaires sains
Non
Sexes éligibles pour l'étude
Tout
La description
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.
Plan d'étude
Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Traitement
- Répartition: Randomisé
- Modèle interventionnel: Affectation parallèle
- Masquage: Tripler
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
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Expérimental: 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
Autres noms:
200 mg sterile liquid vial, dose level 400 mg administered intravenously, one-hour infusion on Day 1, Week 2, 4, 8, and 12
Autres noms:
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.
Autres noms:
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Expérimental: 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
Autres noms:
200 mg sterile liquid vial, dose level 400 mg administered intravenously, one-hour infusion on Day 1, Week 2, 4, 8, and 12
Autres noms:
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.
Autres noms:
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Expérimental: 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
Autres noms:
200 mg sterile liquid vial, dose level 400 mg administered intravenously, one-hour infusion on Day 1, Week 2, 4, 8, and 12
Autres noms:
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.
Autres noms:
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Comparateur 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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Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
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Fold Change From Baseline in Fecal Calprotectin at Week 14
Délai: 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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Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
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Maximum Observed Plasma Concentration (Cmax) for Anrukinzumab
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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)
Délai: 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
Délai: 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
Délai: 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
Délai: 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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Autres mesures de résultats
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
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Clinical Response Rate at Week 14
Délai: 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
Délai: 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.
|
Week 14
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Change From Baseline in Total Mayo Score at Week 14
Délai: 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
Délai: 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.
|
Baseline, Week 14
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Number of Participants With Change From Baseline in Rectal Bleeding at Week 14
Délai: 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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Collaborateurs et enquêteurs
C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.
Parrainer
Publications et liens utiles
La personne responsable de la saisie des informations sur l'étude fournit volontairement ces publications. Il peut s'agir de tout ce qui concerne l'étude.
Dates d'enregistrement des études
Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.
Dates principales de l'étude
Début de l'étude
1 mars 2011
Achèvement primaire (Réel)
1 avril 2013
Achèvement de l'étude (Réel)
1 avril 2013
Dates d'inscription aux études
Première soumission
25 janvier 2011
Première soumission répondant aux critères de contrôle qualité
25 janvier 2011
Première publication (Estimation)
26 janvier 2011
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Estimation)
18 novembre 2014
Dernière mise à jour soumise répondant aux critères de contrôle qualité
10 novembre 2014
Dernière vérification
1 novembre 2014
Plus d'information
Termes liés à cette étude
Termes MeSH pertinents supplémentaires
Autres numéros d'identification d'étude
- B2421003
- IMA-638 Anti-IL13 mAb
- 2010-023762-49 (Numéro EudraCT)
Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .