Pharmacokinetics/Pharmacodynamics Biomarker Study in Active Ulcerative Colitis Patients
10 november 2014 uppdaterad av: 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.
Studieöversikt
Status
Avslutad
Betingelser
Intervention / Behandling
Studietyp
Interventionell
Inskrivning (Faktisk)
84
Fas
- Fas 2
Kontakter och platser
Det här avsnittet innehåller kontaktuppgifter för dem som genomför studien och information om var denna studie genomförs.
Studieorter
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Ruse, Bulgarien, 7002
- MBAL Ruse / MHAT Ruse, Terapevtichno, gastroenterologichno i hematologichno otdelenie
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Sofia, Bulgarien, 1606
- MBAL Voennomeditsinska Akademia / MMA HAT, Klinika po gastroenterologia i hepatologia
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Sofia, Bulgarien, 1750
- DKTs Sveta Anna, Gastroenterologichen cabinet
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Amiens Cedex 01, Frankrike, 80054
- CHU Hopital Nord
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Clichy, Frankrike, 92110
- Hopital Beaujon
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Nantes CEDEX 1, Frankrike, 44093
- CHU Hotel-Dieu
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Alabama
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Birmingham, Alabama, Förenta staterna, 35249
- UAB Hospital Department of Pharmacy
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Birmingham, Alabama, Förenta staterna, 35233
- UAB Hospital
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Birmingham, Alabama, Förenta staterna, 35233
- The Kirkland Clinic
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Birmingham, Alabama, Förenta staterna, 35294
- Administrative Offices
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Birmingham, Alabama, Förenta staterna, 35294
- UAB ACIP
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Arizona
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Phoenix, Arizona, Förenta staterna, 85013
- Dedicated Phase I, Inc.
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Phoenix, Arizona, Förenta staterna, 85006
- Arizona Surgical Center
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California
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Anaheim, California, Förenta staterna, 92801
- Anaheim Clinical Trials, LLC
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Anaheim, California, Förenta staterna, 92801
- AGMG Endoscopy Center
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Santa Ana, California, Förenta staterna, 92705
- West Coast Radiology Center
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Connecticut
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Hamden, Connecticut, Förenta staterna, 06518
- Medical Research Center of Connecticut, LLC
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Hamden, Connecticut, Förenta staterna, 06518
- Gastroenterology Center of Connecticut, PC
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Hamden, Connecticut, Förenta staterna, 06518
- Endoscopy Center of Connecticut, LLC
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Florida
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Sanford, Florida, Förenta staterna, 32771
- International Clinical Research - US, LLC
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Georgia
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Marietta, Georgia, Förenta staterna, 30060
- Gastrointestinal Specialists of Georgia, PC
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Marietta, Georgia, Förenta staterna, 30067
- GI Diagnostics
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Mississippi
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Jackson, Mississippi, Förenta staterna, 39216
- St. Dominic Hospital
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Jackson, Mississippi, Förenta staterna, 39202
- Gastrointestinal Associates, PA
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Jackson, Mississippi, Förenta staterna, 39202
- Gastrointestional Associates, PA
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Tupelo, Mississippi, Förenta staterna, 38801
- North Mississippi Medical Center
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Tupelo, Mississippi, Förenta staterna, 38801
- Digestive Health Specialists, PA
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New York
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Poughkeepsie, New York, Förenta staterna, 12601
- Premier Medical Group of the Hudson Valley
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North Carolina
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Winston-Salem, North Carolina, Förenta staterna, 27103
- PMG Research of Winston-Salem
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Winston-Salem, North Carolina, Förenta staterna, 27103
- Piedmont Gastroenterology Specialists
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Ohio
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Cleveland, Ohio, Förenta staterna, 44106
- University Hospitals Case Medical Center - Division of Gastroenterology and Liver Disease
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Oklahoma
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Oklahoma City, Oklahoma, Förenta staterna, 73104
- Oklahoma Foundation for Digestive Research
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Oklahoma City, Oklahoma, Förenta staterna, 73104
- OU Physicians Building
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Oklahoma City, Oklahoma, Förenta staterna, 73103
- Wheeler and Stuckey, Inc.
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Tennessee
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Germantown, Tennessee, Förenta staterna, 38138
- Memphis Gastroenterology Group, PC
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Memphis, Tennessee, Förenta staterna, 38120
- The West Clinic
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Nashville, Tennessee, Förenta staterna, 37203
- Centennial Medical Center Physicians Park
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Nashville, Tennessee, Förenta staterna, 37203
- Centennial Medical Center Tower Medical Imaging
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Nashville, Tennessee, Förenta staterna, 37203
- Columbia Medical Group - The First Clinic Inc.
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Nashville, Tennessee, Förenta staterna, 37203
- Radiology Alliance
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Texas
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Austin, Texas, Förenta staterna, 78705
- Professional Quality Research, Inc.
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Austin, Texas, Förenta staterna, 78757
- Austin Endoscopy Center
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Austin, Texas, Förenta staterna, 78757
- Austin Gastroenterology, PA
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Houston, Texas, Förenta staterna, 77081
- Texas Center for Drug Development, Inc.
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Round Rocks, Texas, Förenta staterna, 78681
- Austin Gastroenterology, PA
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San Antonio, Texas, Förenta staterna, 78229
- Cardiology Clinic of San Antonio
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San Antonio, Texas, Förenta staterna, 78229
- Gastroenterology Research of San Antonio
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San Antonio, Texas, Förenta staterna, 78229
- San Antonio Endoscopy Center
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Utah
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Murray, Utah, Förenta staterna, 84123
- CNS Pharmacy
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Salt Lake City, Utah, Förenta staterna, 84132
- University of Utah Hospital
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Salt Lake City, Utah, Förenta staterna, 84102
- Alpine Medical Group
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Salt Lake City, Utah, Förenta staterna, 84107
- Wasatch Clinical Research
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Salt Lake City, Utah, Förenta staterna, 84124
- Wasatch Endoscopy Center
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Salt Lake City, Utah, Förenta staterna, 84084
- RGL Medical Services
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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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Amsterdam, Nederländerna, 1081 HV
- VU Medisch Centrum
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Amsterdam, Nederländerna, 1105 AZ
- Academic Medical Center - University of Amsterdam, Dept. of Gastroenterology
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Maastricht, Nederländerna, 6229 HX
- Academisch Ziekenhuis Maastricht
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Warszawa, Polen, 02-507
- Centralny Szpital Kliniczny MSWiA, Klinika Chorob Wewnetrznych i Gastroenterologii
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Bucuresti, Rumänien, 010816
- Sectia Clinica Medicina Interna II
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Barcelona, Spanien, 08036
- Hospital Clinic i Provincial de Barcelona
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Madrid, Spanien, 28007
- Hospital General Universitario Gregorio Marañón
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Berlin, Tyskland, 10117
- Charite - Campus Berlin Mitte
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Heidelberg, Tyskland, 69120
- Universitaetsklinikum Heidelberg
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Kiel, Tyskland, 24105
- Universitaetsklinikum Schleswig-Holstein, Campus Kiel
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Minden, Tyskland, 32423
- Gastroenterologische Gemeinschaftspraxis Minden
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Budapest, Ungern, 1136
- Pannonia Maganorvosi Centrum Kft.
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Budapest, Ungern, 1125
- Szent Janos Korhaz es Eszak-budai Egyesitett Korhazak/I. Belgyogyaszati-Gasztroenterologiai Osztaly
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Szekszard, Ungern, 7100
- Clinfan Kft.
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Linz, Österrike, 4020
- Krankenhaus Der Elisabethinen Linz Gmbh
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St. Poelten, Österrike, 3100
- Landesklinikum St. Poelten
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Wien, Österrike, 1090
- AKH Wien Universitaetsklinik fuer Innere Medizin III
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Deltagandekriterier
Forskare letar efter personer som passar en viss beskrivning, så kallade behörighetskriterier. Några exempel på dessa kriterier är en persons allmänna hälsotillstånd eller tidigare behandlingar.
Urvalskriterier
Åldrar som är berättigade till studier
18 år till 65 år (Vuxen, Äldre vuxen)
Tar emot friska volontärer
Nej
Kön som är behöriga för studier
Allt
Beskrivning
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.
Studieplan
Det här avsnittet ger detaljer om studieplanen, inklusive hur studien är utformad och vad studien mäter.
Hur är studien utformad?
Designdetaljer
- Primärt syfte: Behandling
- Tilldelning: Randomiserad
- Interventionsmodell: Parallellt uppdrag
- Maskning: Trippel
Vapen och interventioner
Deltagargrupp / Arm |
Intervention / Behandling |
|---|---|
|
Experimentell: Arm 1
200 mg PF-05230917, Anrukinzumab active dose level
|
200 mg sterile liquid vial, administered intravenously, one-hour infusion on Day 1, Week 2, 4, 8, and 12
Andra namn:
200 mg sterile liquid vial, dose level 400 mg administered intravenously, one-hour infusion on Day 1, Week 2, 4, 8, and 12
Andra namn:
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.
Andra namn:
|
|
Experimentell: Arm 2
400 mg PF-05230917, Anrukinzumab active dose level
|
200 mg sterile liquid vial, administered intravenously, one-hour infusion on Day 1, Week 2, 4, 8, and 12
Andra namn:
200 mg sterile liquid vial, dose level 400 mg administered intravenously, one-hour infusion on Day 1, Week 2, 4, 8, and 12
Andra namn:
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.
Andra namn:
|
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Experimentell: Arm 3
600 mg PF-05230917, Anrukinzumab active dose level
|
200 mg sterile liquid vial, administered intravenously, one-hour infusion on Day 1, Week 2, 4, 8, and 12
Andra namn:
200 mg sterile liquid vial, dose level 400 mg administered intravenously, one-hour infusion on Day 1, Week 2, 4, 8, and 12
Andra namn:
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.
Andra namn:
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Placebo-jämförare: 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
|
Vad mäter studien?
Primära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
|---|---|---|
|
Fold Change From Baseline in Fecal Calprotectin at Week 14
Tidsram: Baseline, Week 14
|
The fold change from baseline in fecal calprotectin at Week 14, is the ratio of the measurement of fecal calprotectin at Week 14 to baseline measurement; this was calculated as the change from baseline in natural log transformed fecal calprotectin at Week 14.
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Baseline, Week 14
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Sekundära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
|---|---|---|
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Maximum Observed Plasma Concentration (Cmax) for Anrukinzumab
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: Pre-dose, within 1 hour post-end of infusion on Week 12; Week 14, 16, 18, 20, 22, 24, 26, 28, 30, 32
|
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
Tidsram: Pre-dose, within 1 hour post-end of infusion on Week 12; Week 14, 16, 18, 20, 22, 24, 26, 28, 30, 32
|
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
Tidsram: Baseline, Week 2, 4, 8, 12
|
The fold change from baseline in fecal calprotectin at post-baseline visit, is the ratio of the measurement of fecal calprotectin at post-baseline visit to baseline measurement; this was calculated as the change from baseline in natural log transformed fecal calprotectin at post-baseline visit.
|
Baseline, Week 2, 4, 8, 12
|
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Total Interleukin-13 (IL-13) Level
Tidsram: Baseline, Day 2, 4, 7, Week 2, 4, 8, 12, 14, 16, 20, 24, 28, 32
|
Baseline, Day 2, 4, 7, Week 2, 4, 8, 12, 14, 16, 20, 24, 28, 32
|
|
|
Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Tidsram: Baseline up to Week 32
|
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship.
An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
Treatment-emergent are events between first dose of study drug and up to Week 32 that were absent before treatment or that worsened relative to pretreatment state.
All causality AEs included SAEs as well as non-serious AEs, without regard to relationship to the study drug, which occurred during the trial.
|
Baseline up to Week 32
|
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Number of Participants Who Discontinued From the Study Due to Adverse Events
Tidsram: Baseline up to Week 32
|
Baseline up to Week 32
|
|
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Number of Participants With Anti-drug Antibody (ADA) and Neutralizing Antibody
Tidsram: Day 1, Week 4, 8, 12, 14, 16, 20, 24, 28, 32
|
Neutralizing antibody was not analyzed as no participant had positive ADA samples.
|
Day 1, Week 4, 8, 12, 14, 16, 20, 24, 28, 32
|
|
Number of Participants With Change From Baseline in Endoscopic Subscore at Week 14
Tidsram: 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
|
Andra resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
|---|---|---|
|
Clinical Response Rate at Week 14
Tidsram: 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
|
|
Clinical Remission Rate at Week 14
Tidsram: 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
|
|
Change From Baseline in Total Mayo Score at Week 14
Tidsram: 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
|
|
Number of Participants With Change From Baseline in Stool Frequency at Week 14
Tidsram: 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
|
|
Number of Participants With Change From Baseline in Rectal Bleeding at Week 14
Tidsram: 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
|
Samarbetspartners och utredare
Det är här du hittar personer och organisationer som är involverade i denna studie.
Sponsor
Publikationer och användbara länkar
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Användbara länkar
Studieavstämningsdatum
Dessa datum spårar framstegen för inlämningar av studieposter och sammanfattande resultat till ClinicalTrials.gov. Studieposter och rapporterade resultat granskas av National Library of Medicine (NLM) för att säkerställa att de uppfyller specifika kvalitetskontrollstandarder innan de publiceras på den offentliga webbplatsen.
Studera stora datum
Studiestart
1 mars 2011
Primärt slutförande (Faktisk)
1 april 2013
Avslutad studie (Faktisk)
1 april 2013
Studieregistreringsdatum
Först inskickad
25 januari 2011
Först inskickad som uppfyllde QC-kriterierna
25 januari 2011
Första postat (Uppskatta)
26 januari 2011
Uppdateringar av studier
Senaste uppdatering publicerad (Uppskatta)
18 november 2014
Senaste inskickade uppdateringen som uppfyllde QC-kriterierna
10 november 2014
Senast verifierad
1 november 2014
Mer information
Termer relaterade till denna studie
Ytterligare relevanta MeSH-villkor
Andra studie-ID-nummer
- B2421003
- IMA-638 Anti-IL13 mAb
- 2010-023762-49 (EudraCT-nummer)
Denna information hämtades direkt från webbplatsen clinicaltrials.gov utan några ändringar. Om du har några önskemål om att ändra, ta bort eller uppdatera dina studieuppgifter, vänligen kontakta register@clinicaltrials.gov. Så snart en ändring har implementerats på clinicaltrials.gov, kommer denna att uppdateras automatiskt även på vår webbplats .