Pharmacokinetics/Pharmacodynamics Biomarker Study in Active Ulcerative Colitis Patients
10 de novembro de 2014 atualizado por: 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.
Visão geral do estudo
Status
Concluído
Condições
Intervenção / Tratamento
Tipo de estudo
Intervencional
Inscrição (Real)
84
Estágio
- Fase 2
Contactos e Locais
Esta seção fornece os detalhes de contato para aqueles que conduzem o estudo e informações sobre onde este estudo está sendo realizado.
Locais de estudo
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Berlin, Alemanha, 10117
- Charite - Campus Berlin Mitte
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Heidelberg, Alemanha, 69120
- Universitaetsklinikum Heidelberg
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Kiel, Alemanha, 24105
- Universitaetsklinikum Schleswig-Holstein, Campus Kiel
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Minden, Alemanha, 32423
- Gastroenterologische Gemeinschaftspraxis Minden
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Ruse, Bulgária, 7002
- MBAL Ruse / MHAT Ruse, Terapevtichno, gastroenterologichno i hematologichno otdelenie
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Sofia, Bulgária, 1606
- MBAL Voennomeditsinska Akademia / MMA HAT, Klinika po gastroenterologia i hepatologia
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Sofia, Bulgária, 1750
- DKTs Sveta Anna, Gastroenterologichen cabinet
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Alberta
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Calgary, Alberta, Canadá, T2N 4Z6
- Heritage Medical Research Clinic - University Of Calgary
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British Columbia
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Vancouver, British Columbia, Canadá, V5Z 1M9
- Vancouver Coastal Health - Vancouver General Hospital
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Vancouver, British Columbia, Canadá, V5Z 1M9
- Vancouver General Hospital - The Gordon and Leslie Diamond Centre
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Ontario
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Kingston, Ontario, Canadá, K7L 5G2
- The Religious Hospitallers of St. Joseph of the Hotel Dieu of Kingston
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Toronto, Ontario, Canadá, M4N 3M5
- Sunnybrook Health Sciences Centre
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Barcelona, Espanha, 08036
- Hospital Clinic i Provincial de Barcelona
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Madrid, Espanha, 28007
- Hospital General Universitario Gregorio Marañon
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Alabama
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Birmingham, Alabama, Estados Unidos, 35249
- UAB Hospital Department of Pharmacy
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Birmingham, Alabama, Estados Unidos, 35233
- UAB Hospital
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Birmingham, Alabama, Estados Unidos, 35233
- The Kirkland Clinic
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Birmingham, Alabama, Estados Unidos, 35294
- Administrative Offices
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Birmingham, Alabama, Estados Unidos, 35294
- UAB ACIP
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Arizona
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Phoenix, Arizona, Estados Unidos, 85013
- Dedicated Phase I, Inc.
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Phoenix, Arizona, Estados Unidos, 85006
- Arizona Surgical Center
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California
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Anaheim, California, Estados Unidos, 92801
- Anaheim Clinical Trials, LLC
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Anaheim, California, Estados Unidos, 92801
- AGMG Endoscopy Center
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Santa Ana, California, Estados Unidos, 92705
- West Coast Radiology Center
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Connecticut
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Hamden, Connecticut, Estados Unidos, 06518
- Medical Research Center of Connecticut, LLC
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Hamden, Connecticut, Estados Unidos, 06518
- Gastroenterology Center of Connecticut, PC
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Hamden, Connecticut, Estados Unidos, 06518
- Endoscopy Center of Connecticut, LLC
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Florida
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Sanford, Florida, Estados Unidos, 32771
- International Clinical Research - US, LLC
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Georgia
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Marietta, Georgia, Estados Unidos, 30060
- Gastrointestinal Specialists of Georgia, PC
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Marietta, Georgia, Estados Unidos, 30067
- GI Diagnostics
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Mississippi
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Jackson, Mississippi, Estados Unidos, 39216
- St. Dominic Hospital
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Jackson, Mississippi, Estados Unidos, 39202
- Gastrointestinal Associates, PA
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Jackson, Mississippi, Estados Unidos, 39202
- Gastrointestional Associates, PA
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Tupelo, Mississippi, Estados Unidos, 38801
- North Mississippi Medical Center
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Tupelo, Mississippi, Estados Unidos, 38801
- Digestive Health Specialists, PA
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New York
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Poughkeepsie, New York, Estados Unidos, 12601
- Premier Medical Group of the Hudson Valley
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North Carolina
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Winston-Salem, North Carolina, Estados Unidos, 27103
- PMG Research of Winston-Salem
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Winston-Salem, North Carolina, Estados Unidos, 27103
- Piedmont Gastroenterology Specialists
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Ohio
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Cleveland, Ohio, Estados Unidos, 44106
- University Hospitals Case Medical Center - Division of Gastroenterology and Liver Disease
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Oklahoma
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Oklahoma City, Oklahoma, Estados Unidos, 73104
- Oklahoma Foundation for Digestive Research
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Oklahoma City, Oklahoma, Estados Unidos, 73104
- OU Physicians Building
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Oklahoma City, Oklahoma, Estados Unidos, 73103
- Wheeler and Stuckey, Inc.
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Tennessee
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Germantown, Tennessee, Estados Unidos, 38138
- Memphis Gastroenterology Group, PC
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Memphis, Tennessee, Estados Unidos, 38120
- The West Clinic
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Nashville, Tennessee, Estados Unidos, 37203
- Centennial Medical Center Physicians Park
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Nashville, Tennessee, Estados Unidos, 37203
- Centennial Medical Center Tower Medical Imaging
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Nashville, Tennessee, Estados Unidos, 37203
- Columbia Medical Group - The First Clinic Inc.
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Nashville, Tennessee, Estados Unidos, 37203
- Radiology Alliance
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Texas
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Austin, Texas, Estados Unidos, 78705
- Professional Quality Research, Inc.
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Austin, Texas, Estados Unidos, 78757
- Austin Endoscopy Center
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Austin, Texas, Estados Unidos, 78757
- Austin Gastroenterology, PA
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Houston, Texas, Estados Unidos, 77081
- Texas Center for Drug Development, Inc.
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Round Rocks, Texas, Estados Unidos, 78681
- Austin Gastroenterology, PA
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San Antonio, Texas, Estados Unidos, 78229
- Cardiology Clinic of San Antonio
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San Antonio, Texas, Estados Unidos, 78229
- Gastroenterology Research of San Antonio
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San Antonio, Texas, Estados Unidos, 78229
- San Antonio Endoscopy Center
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Utah
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Murray, Utah, Estados Unidos, 84123
- CNS Pharmacy
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Salt Lake City, Utah, Estados Unidos, 84132
- University of Utah Hospital
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Salt Lake City, Utah, Estados Unidos, 84102
- Alpine Medical Group
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Salt Lake City, Utah, Estados Unidos, 84107
- Wasatch Clinical Research
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Salt Lake City, Utah, Estados Unidos, 84124
- Wasatch Endoscopy Center
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Salt Lake City, Utah, Estados Unidos, 84084
- RGL Medical Services
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Amiens Cedex 01, França, 80054
- CHU Hopital Nord
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Clichy, França, 92110
- Hôpital Beaujon
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Nantes CEDEX 1, França, 44093
- CHU Hôtel-Dieu
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Amsterdam, Holanda, 1081 HV
- VU Medisch Centrum
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Amsterdam, Holanda, 1105 AZ
- Academic Medical Center - University of Amsterdam, Dept. of Gastroenterology
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Maastricht, Holanda, 6229 HX
- Academisch Ziekenhuis Maastricht
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Budapest, Hungria, 1136
- Pannonia Maganorvosi Centrum Kft.
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Budapest, Hungria, 1125
- Szent Janos Korhaz es Eszak-budai Egyesitett Korhazak/I. Belgyogyaszati-Gasztroenterologiai Osztaly
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Szekszard, Hungria, 7100
- Clinfan Kft.
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Warszawa, Polônia, 02-507
- Centralny Szpital Kliniczny MSWiA, Klinika Chorob Wewnetrznych i Gastroenterologii
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Bucuresti, Romênia, 010816
- Sectia Clinica Medicina Interna II
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Linz, Áustria, 4020
- Krankenhaus Der Elisabethinen Linz Gmbh
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St. Poelten, Áustria, 3100
- Landesklinikum St. Poelten
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Wien, Áustria, 1090
- AKH Wien Universitaetsklinik fuer Innere Medizin III
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Critérios de participação
Os pesquisadores procuram pessoas que se encaixem em uma determinada descrição, chamada de critérios de elegibilidade. Alguns exemplos desses critérios são a condição geral de saúde de uma pessoa ou tratamentos anteriores.
Critérios de elegibilidade
Idades elegíveis para estudo
18 anos a 65 anos (Adulto, Adulto mais velho)
Aceita Voluntários Saudáveis
Não
Gêneros Elegíveis para o Estudo
Tudo
Descrição
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.
Plano de estudo
Esta seção fornece detalhes do plano de estudo, incluindo como o estudo é projetado e o que o estudo está medindo.
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Tratamento
- Alocação: Randomizado
- Modelo Intervencional: Atribuição Paralela
- Mascaramento: Triplo
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
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Experimental: 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
Outros nomes:
200 mg sterile liquid vial, dose level 400 mg administered intravenously, one-hour infusion on Day 1, Week 2, 4, 8, and 12
Outros nomes:
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.
Outros nomes:
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Experimental: 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
Outros nomes:
200 mg sterile liquid vial, dose level 400 mg administered intravenously, one-hour infusion on Day 1, Week 2, 4, 8, and 12
Outros nomes:
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.
Outros nomes:
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Experimental: 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
Outros nomes:
200 mg sterile liquid vial, dose level 400 mg administered intravenously, one-hour infusion on Day 1, Week 2, 4, 8, and 12
Outros nomes:
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.
Outros nomes:
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Comparador de 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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O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
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Fold Change From Baseline in Fecal Calprotectin at Week 14
Prazo: 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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Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
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Maximum Observed Plasma Concentration (Cmax) for Anrukinzumab
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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)
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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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Outras medidas de resultado
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Clinical Response Rate at Week 14
Prazo: 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
Prazo: Week 14
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Clinical remission rate is defined as percentage of participants with a total Mayo score less than or equal to 2, with no individual subscore greater than 1 at post baseline visit.
The Mayo score is a tool designed to measure disease activity for ulcerative colitis.
The Mayo score ranges from 0 to 12 points and consists of 4 subscores (stool frequency, rectal bleeding, findings on flexible sigmoidoscopy and physician's global assessment), each subscore is graded from 0 to 3 with the higher score indicating more severe disease activity.
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Week 14
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Change From Baseline in Total Mayo Score at Week 14
Prazo: 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
Prazo: Baseline, Week 14
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Stool frequency is a sub score of Mayo score used to measure the disease activity of ulcerative colitis.
The score for stool frequency ranges from 0 to 3, where higher score indicates more severe disease activity.
Participant's score for stool frequency at Week 14 was specified as improved (decrease), no change and worsened (increase) compared to their baseline score.
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Baseline, Week 14
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Number of Participants With Change From Baseline in Rectal Bleeding at Week 14
Prazo: 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.
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Baseline, Week 14
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Colaboradores e Investigadores
É aqui que você encontrará pessoas e organizações envolvidas com este estudo.
Patrocinador
Publicações e links úteis
A pessoa responsável por inserir informações sobre o estudo fornece voluntariamente essas publicações. Estes podem ser sobre qualquer coisa relacionada ao estudo.
Datas de registro do estudo
Essas datas acompanham o progresso do registro do estudo e os envios de resumo dos resultados para ClinicalTrials.gov. Os registros do estudo e os resultados relatados são revisados pela National Library of Medicine (NLM) para garantir que atendam aos padrões específicos de controle de qualidade antes de serem publicados no site público.
Datas Principais do Estudo
Início do estudo
1 de março de 2011
Conclusão Primária (Real)
1 de abril de 2013
Conclusão do estudo (Real)
1 de abril de 2013
Datas de inscrição no estudo
Enviado pela primeira vez
25 de janeiro de 2011
Enviado pela primeira vez que atendeu aos critérios de CQ
25 de janeiro de 2011
Primeira postagem (Estimativa)
26 de janeiro de 2011
Atualizações de registro de estudo
Última Atualização Postada (Estimativa)
18 de novembro de 2014
Última atualização enviada que atendeu aos critérios de controle de qualidade
10 de novembro de 2014
Última verificação
1 de novembro de 2014
Mais Informações
Termos relacionados a este estudo
Palavras-chave
Termos MeSH relevantes adicionais
Outros números de identificação do estudo
- B2421003
- IMA-638 Anti-IL13 mAb
- 2010-023762-49 (Número EudraCT)
Essas informações foram obtidas diretamente do site clinicaltrials.gov sem nenhuma alteração. Se você tiver alguma solicitação para alterar, remover ou atualizar os detalhes do seu estudo, entre em contato com register@clinicaltrials.gov. Assim que uma alteração for implementada em clinicaltrials.gov, ela também será atualizada automaticamente em nosso site .