Pharmacokinetics/Pharmacodynamics Biomarker Study in Active Ulcerative Colitis Patients
10. november 2014 oppdatert 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.
Studieoversikt
Status
Fullført
Forhold
Intervensjon / Behandling
Studietype
Intervensjonell
Registrering (Faktiske)
84
Fase
- Fase 2
Kontakter og plasseringer
Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.
Studiesteder
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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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Alabama
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Birmingham, Alabama, Forente stater, 35249
- UAB Hospital Department of Pharmacy
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Birmingham, Alabama, Forente stater, 35233
- UAB Hospital
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Birmingham, Alabama, Forente stater, 35233
- The Kirkland Clinic
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Birmingham, Alabama, Forente stater, 35294
- Administrative Offices
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Birmingham, Alabama, Forente stater, 35294
- UAB ACIP
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Arizona
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Phoenix, Arizona, Forente stater, 85013
- Dedicated Phase I, Inc.
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Phoenix, Arizona, Forente stater, 85006
- Arizona Surgical Center
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California
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Anaheim, California, Forente stater, 92801
- Anaheim Clinical Trials, LLC
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Anaheim, California, Forente stater, 92801
- AGMG Endoscopy Center
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Santa Ana, California, Forente stater, 92705
- West Coast Radiology Center
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Connecticut
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Hamden, Connecticut, Forente stater, 06518
- Medical Research Center of Connecticut, LLC
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Hamden, Connecticut, Forente stater, 06518
- Gastroenterology Center of Connecticut, PC
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Hamden, Connecticut, Forente stater, 06518
- Endoscopy Center of Connecticut, LLC
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Florida
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Sanford, Florida, Forente stater, 32771
- International Clinical Research - US, LLC
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Georgia
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Marietta, Georgia, Forente stater, 30060
- Gastrointestinal Specialists of Georgia, PC
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Marietta, Georgia, Forente stater, 30067
- GI Diagnostics
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Mississippi
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Jackson, Mississippi, Forente stater, 39216
- St. Dominic Hospital
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Jackson, Mississippi, Forente stater, 39202
- Gastrointestinal Associates, PA
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Jackson, Mississippi, Forente stater, 39202
- Gastrointestional Associates, PA
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Tupelo, Mississippi, Forente stater, 38801
- North Mississippi Medical Center
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Tupelo, Mississippi, Forente stater, 38801
- Digestive Health Specialists, PA
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New York
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Poughkeepsie, New York, Forente stater, 12601
- Premier Medical Group of the Hudson Valley
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North Carolina
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Winston-Salem, North Carolina, Forente stater, 27103
- PMG Research of Winston-Salem
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Winston-Salem, North Carolina, Forente stater, 27103
- Piedmont Gastroenterology Specialists
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Ohio
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Cleveland, Ohio, Forente stater, 44106
- University Hospitals Case Medical Center - Division of Gastroenterology and Liver Disease
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Oklahoma
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Oklahoma City, Oklahoma, Forente stater, 73104
- Oklahoma Foundation for Digestive Research
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Oklahoma City, Oklahoma, Forente stater, 73104
- OU Physicians Building
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Oklahoma City, Oklahoma, Forente stater, 73103
- Wheeler and Stuckey, Inc.
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Tennessee
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Germantown, Tennessee, Forente stater, 38138
- Memphis Gastroenterology Group, PC
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Memphis, Tennessee, Forente stater, 38120
- The West Clinic
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Nashville, Tennessee, Forente stater, 37203
- Centennial Medical Center Physicians Park
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Nashville, Tennessee, Forente stater, 37203
- Centennial Medical Center Tower Medical Imaging
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Nashville, Tennessee, Forente stater, 37203
- Columbia Medical Group - The First Clinic Inc.
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Nashville, Tennessee, Forente stater, 37203
- Radiology Alliance
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Texas
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Austin, Texas, Forente stater, 78705
- Professional Quality Research, Inc.
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Austin, Texas, Forente stater, 78757
- Austin Endoscopy Center
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Austin, Texas, Forente stater, 78757
- Austin Gastroenterology, PA
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Houston, Texas, Forente stater, 77081
- Texas Center for Drug Development, Inc.
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Round Rocks, Texas, Forente stater, 78681
- Austin Gastroenterology, PA
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San Antonio, Texas, Forente stater, 78229
- Cardiology Clinic of San Antonio
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San Antonio, Texas, Forente stater, 78229
- Gastroenterology Research of San Antonio
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San Antonio, Texas, Forente stater, 78229
- San Antonio Endoscopy Center
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Utah
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Murray, Utah, Forente stater, 84123
- CNS Pharmacy
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Salt Lake City, Utah, Forente stater, 84132
- University of Utah Hospital
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Salt Lake City, Utah, Forente stater, 84102
- Alpine Medical Group
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Salt Lake City, Utah, Forente stater, 84107
- Wasatch Clinical Research
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Salt Lake City, Utah, Forente stater, 84124
- Wasatch Endoscopy Center
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Salt Lake City, Utah, Forente stater, 84084
- RGL Medical Services
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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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Amsterdam, Nederland, 1081 HV
- VU Medisch Centrum
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Amsterdam, Nederland, 1105 AZ
- Academic Medical Center - University of Amsterdam, Dept. of Gastroenterology
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Maastricht, Nederland, 6229 HX
- Academisch Ziekenhuis Maastricht
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Warszawa, Polen, 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, Spania, 08036
- Hospital Clinic i Provincial de Barcelona
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Madrid, Spania, 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, Ungarn, 1136
- Pannonia Maganorvosi Centrum Kft.
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Budapest, Ungarn, 1125
- Szent Janos Korhaz es Eszak-budai Egyesitett Korhazak/I. Belgyogyaszati-Gasztroenterologiai Osztaly
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Szekszard, Ungarn, 7100
- Clinfan Kft.
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Linz, Østerrike, 4020
- Krankenhaus Der Elisabethinen Linz Gmbh
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St. Poelten, Østerrike, 3100
- Landesklinikum St. Poelten
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Wien, Østerrike, 1090
- AKH Wien Universitaetsklinik fuer Innere Medizin III
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Deltakelseskriterier
Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
18 år til 65 år (Voksen, Eldre voksen)
Tar imot friske frivillige
Nei
Kjønn som er kvalifisert for studier
Alle
Beskrivelse
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
Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Behandling
- Tildeling: Randomisert
- Intervensjonsmodell: Parallell tildeling
- Masking: Trippel
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
|---|---|
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Eksperimentell: 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
Andre navn:
200 mg sterile liquid vial, dose level 400 mg administered intravenously, one-hour infusion on Day 1, Week 2, 4, 8, and 12
Andre navn:
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.
Andre navn:
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Eksperimentell: 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
Andre navn:
200 mg sterile liquid vial, dose level 400 mg administered intravenously, one-hour infusion on Day 1, Week 2, 4, 8, and 12
Andre navn:
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.
Andre navn:
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Eksperimentell: 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
Andre navn:
200 mg sterile liquid vial, dose level 400 mg administered intravenously, one-hour infusion on Day 1, Week 2, 4, 8, and 12
Andre navn:
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.
Andre navn:
|
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Placebo komparator: 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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Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
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Fold Change From Baseline in Fecal Calprotectin at Week 14
Tidsramme: 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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Sekundære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
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Maximum Observed Plasma Concentration (Cmax) for Anrukinzumab
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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.
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Baseline, Week 2, 4, 8, 12
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Total Interleukin-13 (IL-13) Level
Tidsramme: 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
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Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
|
Andre resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
|
Clinical Response Rate at Week 14
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
|
Samarbeidspartnere og etterforskere
Det er her du vil finne personer og organisasjoner som er involvert i denne studien.
Sponsor
Publikasjoner og nyttige lenker
Den som er ansvarlig for å legge inn informasjon om studien leverer frivillig disse publikasjonene. Disse kan handle om alt relatert til studiet.
Hjelpsomme linker
Studierekorddatoer
Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.
Studer hoveddatoer
Studiestart
1. mars 2011
Primær fullføring (Faktiske)
1. april 2013
Studiet fullført (Faktiske)
1. april 2013
Datoer for studieregistrering
Først innsendt
25. januar 2011
Først innsendt som oppfylte QC-kriteriene
25. januar 2011
Først lagt ut (Anslag)
26. januar 2011
Oppdateringer av studieposter
Sist oppdatering lagt ut (Anslag)
18. november 2014
Siste oppdatering sendt inn som oppfylte QC-kriteriene
10. november 2014
Sist bekreftet
1. november 2014
Mer informasjon
Begreper knyttet til denne studien
Ytterligere relevante MeSH-vilkår
Andre studie-ID-numre
- B2421003
- IMA-638 Anti-IL13 mAb
- 2010-023762-49 (EudraCT-nummer)
Denne informasjonen ble hentet direkte fra nettstedet clinicaltrials.gov uten noen endringer. Hvis du har noen forespørsler om å endre, fjerne eller oppdatere studiedetaljene dine, vennligst kontakt register@clinicaltrials.gov. Så snart en endring er implementert på clinicaltrials.gov, vil denne også bli oppdatert automatisk på nettstedet vårt. .