Pharmacokinetics/Pharmacodynamics Biomarker Study in Active Ulcerative Colitis Patients
maanantai 10. marraskuuta 2014 päivittänyt: 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.
Tutkimuksen yleiskatsaus
Tila
Valmis
Ehdot
Interventio / Hoito
Opintotyyppi
Interventio
Ilmoittautuminen (Todellinen)
84
Vaihe
- Vaihe 2
Yhteystiedot ja paikat
Tässä osiossa on tutkimuksen suorittajien yhteystiedot ja tiedot siitä, missä tämä tutkimus suoritetaan.
Opiskelupaikat
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Amsterdam, Alankomaat, 1081 HV
- VU Medisch Centrum
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Amsterdam, Alankomaat, 1105 AZ
- Academic Medical Center - University of Amsterdam, Dept. of Gastroenterology
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Maastricht, Alankomaat, 6229 HX
- Academisch Ziekenhuis Maastricht
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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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Barcelona, Espanja, 08036
- Hospital Clinic i Provincial de Barcelona
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Madrid, Espanja, 28007
- Hospital General Universitario Gregorio Marañón
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Linz, Itävalta, 4020
- Krankenhaus Der Elisabethinen Linz Gmbh
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St. Poelten, Itävalta, 3100
- Landesklinikum St. Poelten
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Wien, Itävalta, 1090
- AKH Wien Universitaetsklinik fuer Innere Medizin III
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Alberta
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Calgary, Alberta, Kanada, T2N 4Z6
- Heritage Medical Research Clinic - University Of Calgary
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British Columbia
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Vancouver, British Columbia, Kanada, V5Z 1M9
- Vancouver Coastal Health - Vancouver General Hospital
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Vancouver, British Columbia, Kanada, V5Z 1M9
- Vancouver General Hospital - The Gordon and Leslie Diamond Centre
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Ontario
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Kingston, Ontario, Kanada, K7L 5G2
- The Religious Hospitallers of St. Joseph of the Hotel Dieu of Kingston
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Toronto, Ontario, Kanada, M4N 3M5
- Sunnybrook Health Sciences Centre
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Warszawa, Puola, 02-507
- Centralny Szpital Kliniczny MSWiA, Klinika Chorob Wewnetrznych i Gastroenterologii
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Amiens Cedex 01, Ranska, 80054
- CHU Hopital Nord
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Clichy, Ranska, 92110
- Hôpital Beaujon
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Nantes CEDEX 1, Ranska, 44093
- CHU Hôtel-Dieu
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Bucuresti, Romania, 010816
- Sectia Clinica Medicina Interna II
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Berlin, Saksa, 10117
- Charite - Campus Berlin Mitte
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Heidelberg, Saksa, 69120
- Universitaetsklinikum Heidelberg
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Kiel, Saksa, 24105
- Universitaetsklinikum Schleswig-Holstein, Campus Kiel
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Minden, Saksa, 32423
- Gastroenterologische Gemeinschaftspraxis Minden
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Budapest, Unkari, 1136
- Pannonia Maganorvosi Centrum Kft.
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Budapest, Unkari, 1125
- Szent Janos Korhaz es Eszak-budai Egyesitett Korhazak/I. Belgyogyaszati-Gasztroenterologiai Osztaly
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Szekszard, Unkari, 7100
- Clinfan Kft.
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Alabama
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Birmingham, Alabama, Yhdysvallat, 35249
- UAB Hospital Department of Pharmacy
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Birmingham, Alabama, Yhdysvallat, 35233
- UAB Hospital
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Birmingham, Alabama, Yhdysvallat, 35233
- The Kirkland Clinic
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Birmingham, Alabama, Yhdysvallat, 35294
- Administrative Offices
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Birmingham, Alabama, Yhdysvallat, 35294
- UAB ACIP
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Arizona
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Phoenix, Arizona, Yhdysvallat, 85013
- Dedicated Phase I, Inc.
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Phoenix, Arizona, Yhdysvallat, 85006
- Arizona Surgical Center
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California
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Anaheim, California, Yhdysvallat, 92801
- Anaheim Clinical Trials, LLC
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Anaheim, California, Yhdysvallat, 92801
- AGMG Endoscopy Center
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Santa Ana, California, Yhdysvallat, 92705
- West Coast Radiology Center
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Connecticut
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Hamden, Connecticut, Yhdysvallat, 06518
- Medical Research Center of Connecticut, LLC
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Hamden, Connecticut, Yhdysvallat, 06518
- Gastroenterology Center of Connecticut, PC
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Hamden, Connecticut, Yhdysvallat, 06518
- Endoscopy Center of Connecticut, LLC
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Florida
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Sanford, Florida, Yhdysvallat, 32771
- International Clinical Research - US, LLC
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Georgia
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Marietta, Georgia, Yhdysvallat, 30060
- Gastrointestinal Specialists of Georgia, PC
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Marietta, Georgia, Yhdysvallat, 30067
- GI Diagnostics
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Mississippi
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Jackson, Mississippi, Yhdysvallat, 39216
- St. Dominic Hospital
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Jackson, Mississippi, Yhdysvallat, 39202
- Gastrointestinal Associates, PA
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Jackson, Mississippi, Yhdysvallat, 39202
- Gastrointestional Associates, PA
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Tupelo, Mississippi, Yhdysvallat, 38801
- North Mississippi Medical Center
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Tupelo, Mississippi, Yhdysvallat, 38801
- Digestive Health Specialists, PA
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New York
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Poughkeepsie, New York, Yhdysvallat, 12601
- Premier Medical Group of the Hudson Valley
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North Carolina
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Winston-Salem, North Carolina, Yhdysvallat, 27103
- PMG Research of Winston-Salem
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Winston-Salem, North Carolina, Yhdysvallat, 27103
- Piedmont Gastroenterology Specialists
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Ohio
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Cleveland, Ohio, Yhdysvallat, 44106
- University Hospitals Case Medical Center - Division of Gastroenterology and Liver Disease
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Oklahoma
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Oklahoma City, Oklahoma, Yhdysvallat, 73104
- Oklahoma Foundation for Digestive Research
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Oklahoma City, Oklahoma, Yhdysvallat, 73104
- OU Physicians Building
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Oklahoma City, Oklahoma, Yhdysvallat, 73103
- Wheeler and Stuckey, Inc.
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Tennessee
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Germantown, Tennessee, Yhdysvallat, 38138
- Memphis Gastroenterology Group, PC
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Memphis, Tennessee, Yhdysvallat, 38120
- The West Clinic
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Nashville, Tennessee, Yhdysvallat, 37203
- Centennial Medical Center Physicians Park
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Nashville, Tennessee, Yhdysvallat, 37203
- Centennial Medical Center Tower Medical Imaging
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Nashville, Tennessee, Yhdysvallat, 37203
- Columbia Medical Group - The First Clinic Inc.
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Nashville, Tennessee, Yhdysvallat, 37203
- Radiology Alliance
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Texas
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Austin, Texas, Yhdysvallat, 78705
- Professional Quality Research, Inc.
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Austin, Texas, Yhdysvallat, 78757
- Austin Endoscopy Center
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Austin, Texas, Yhdysvallat, 78757
- Austin Gastroenterology, PA
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Houston, Texas, Yhdysvallat, 77081
- Texas Center for Drug Development, Inc.
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Round Rocks, Texas, Yhdysvallat, 78681
- Austin Gastroenterology, PA
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San Antonio, Texas, Yhdysvallat, 78229
- Cardiology Clinic of San Antonio
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San Antonio, Texas, Yhdysvallat, 78229
- Gastroenterology Research of San Antonio
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San Antonio, Texas, Yhdysvallat, 78229
- San Antonio Endoscopy Center
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Utah
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Murray, Utah, Yhdysvallat, 84123
- CNS Pharmacy
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Salt Lake City, Utah, Yhdysvallat, 84132
- University of Utah Hospital
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Salt Lake City, Utah, Yhdysvallat, 84102
- Alpine Medical Group
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Salt Lake City, Utah, Yhdysvallat, 84107
- Wasatch Clinical Research
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Salt Lake City, Utah, Yhdysvallat, 84124
- Wasatch Endoscopy Center
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Salt Lake City, Utah, Yhdysvallat, 84084
- RGL Medical Services
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Osallistumiskriteerit
Tutkijat etsivät ihmisiä, jotka sopivat tiettyyn kuvaukseen, jota kutsutaan kelpoisuuskriteereiksi. Joitakin esimerkkejä näistä kriteereistä ovat henkilön yleinen terveydentila tai aiemmat hoidot.
Kelpoisuusvaatimukset
Opintokelpoiset iät
18 vuotta - 65 vuotta (Aikuinen, Vanhempi Aikuinen)
Hyväksyy terveitä vapaaehtoisia
Ei
Sukupuolet, jotka voivat opiskella
Kaikki
Kuvaus
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.
Opintosuunnitelma
Tässä osiossa on tietoja tutkimussuunnitelmasta, mukaan lukien kuinka tutkimus on suunniteltu ja mitä tutkimuksella mitataan.
Miten tutkimus on suunniteltu?
Suunnittelun yksityiskohdat
- Ensisijainen käyttötarkoitus: Hoito
- Jako: Satunnaistettu
- Inventiomalli: Rinnakkaistehtävä
- Naamiointi: Kolminkertaistaa
Aseet ja interventiot
Osallistujaryhmä / Arm |
Interventio / Hoito |
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Kokeellinen: 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
Muut nimet:
200 mg sterile liquid vial, dose level 400 mg administered intravenously, one-hour infusion on Day 1, Week 2, 4, 8, and 12
Muut nimet:
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.
Muut nimet:
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Kokeellinen: 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
Muut nimet:
200 mg sterile liquid vial, dose level 400 mg administered intravenously, one-hour infusion on Day 1, Week 2, 4, 8, and 12
Muut nimet:
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.
Muut nimet:
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Kokeellinen: 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
Muut nimet:
200 mg sterile liquid vial, dose level 400 mg administered intravenously, one-hour infusion on Day 1, Week 2, 4, 8, and 12
Muut nimet:
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.
Muut nimet:
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Placebo Comparator: 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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Mitä tutkimuksessa mitataan?
Ensisijaiset tulostoimenpiteet
Tulosmittaus |
Toimenpiteen kuvaus |
Aikaikkuna |
|---|---|---|
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Fold Change From Baseline in Fecal Calprotectin at Week 14
Aikaikkuna: 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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Toissijaiset tulostoimenpiteet
Tulosmittaus |
Toimenpiteen kuvaus |
Aikaikkuna |
|---|---|---|
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Maximum Observed Plasma Concentration (Cmax) for Anrukinzumab
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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)
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: Baseline, 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
|
Muut tulostoimenpiteet
Tulosmittaus |
Toimenpiteen kuvaus |
Aikaikkuna |
|---|---|---|
|
Clinical Response Rate at Week 14
Aikaikkuna: 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
|
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Clinical Remission Rate at Week 14
Aikaikkuna: 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
|
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Change From Baseline in Total Mayo Score at Week 14
Aikaikkuna: Baseline, 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
|
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Number of Participants With Change From Baseline in Stool Frequency at Week 14
Aikaikkuna: 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
Aikaikkuna: 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
|
Yhteistyökumppanit ja tutkijat
Täältä löydät tähän tutkimukseen osallistuvat ihmiset ja organisaatiot.
Sponsori
Julkaisuja ja hyödyllisiä linkkejä
Tutkimusta koskevien tietojen syöttämisestä vastaava henkilö toimittaa nämä julkaisut vapaaehtoisesti. Nämä voivat koskea mitä tahansa tutkimukseen liittyvää.
Hyödyllisiä linkkejä
Opintojen ennätyspäivät
Nämä päivämäärät seuraavat ClinicalTrials.gov-sivustolle lähetettyjen tutkimustietueiden ja yhteenvetojen edistymistä. National Library of Medicine (NLM) tarkistaa tutkimustiedot ja raportoidut tulokset varmistaakseen, että ne täyttävät tietyt laadunvalvontastandardit, ennen kuin ne julkaistaan julkisella verkkosivustolla.
Opi tärkeimmät päivämäärät
Opiskelun aloitus
Tiistai 1. maaliskuuta 2011
Ensisijainen valmistuminen (Todellinen)
Maanantai 1. huhtikuuta 2013
Opintojen valmistuminen (Todellinen)
Maanantai 1. huhtikuuta 2013
Opintoihin ilmoittautumispäivät
Ensimmäinen lähetetty
Tiistai 25. tammikuuta 2011
Ensimmäinen toimitettu, joka täytti QC-kriteerit
Tiistai 25. tammikuuta 2011
Ensimmäinen Lähetetty (Arvio)
Keskiviikko 26. tammikuuta 2011
Tutkimustietojen päivitykset
Viimeisin päivitys julkaistu (Arvio)
Tiistai 18. marraskuuta 2014
Viimeisin lähetetty päivitys, joka täytti QC-kriteerit
Maanantai 10. marraskuuta 2014
Viimeksi vahvistettu
Lauantai 1. marraskuuta 2014
Lisää tietoa
Tähän tutkimukseen liittyvät termit
Avainsanat
Muita asiaankuuluvia MeSH-ehtoja
Muut tutkimustunnusnumerot
- B2421003
- IMA-638 Anti-IL13 mAb
- 2010-023762-49 (EudraCT-numero)
Nämä tiedot haettiin suoraan verkkosivustolta clinicaltrials.gov ilman muutoksia. Jos sinulla on pyyntöjä muuttaa, poistaa tai päivittää tutkimustietojasi, ota yhteyttä register@clinicaltrials.gov. Heti kun muutos on otettu käyttöön osoitteessa clinicaltrials.gov, se päivitetään automaattisesti myös verkkosivustollemme .