Study of CMX001 to Prevent/Control Cytomegalovirus Infection in R+ Hematopoietic Stem Cell Transplant Recipients
28 de junio de 2021 actualizado por: Chimerix
A Multicenter, Randomized, Double-blind, Placebo-controlled, Dose-escalation Study of the Safety, Tolerability and Ability of CMX001 to Prevent or Control CMV Infection in R+ Hematopoietic Stem Cell Transplant Recipients
This was a multicenter, randomized, double-blind, placebo-controlled, dose-escalation study of brincidofovir (BCV) administered orally once or twice weekly for up to 11 weeks.
Dosing was initiated immediately following engraftment (between Days 14-30 post-transplant) to prevent/control cytomegalovirus (CMV) infection or prevent disease in R+ hematopoietic stem cell transplant (HCT) recipients.
Descripción general del estudio
Estado
Terminado
Condiciones
Intervención / Tratamiento
Descripción detallada
This was to be a 2-part study.
Part 1 was a randomized, double-blind, placebo-controlled, dose-escalation study of multiple doses of oral brincidofovir (BCV) in R+ hematopoietic stem cell transplant (HCT) recipients.
In Part 2, one of the dose levels administered in Part 1 was to be tested against placebo to evaluate the statistical significance of BCV as a therapy for preventing progression of cytomegalovirus (CMV) infection or preventing CMV disease.
The first 3 dose-escalating cohorts in Part 1 were to include 32 subjects within each cohort (24 randomized to receive oral BCV and 8 randomized to receive placebo in a 3:1 ratio) for a total of 96 planned subjects.
Following completion of the first 3 cohorts and subsequent safety review of the data, up to an additional 3 cohorts of 32 subjects each could have been enrolled.
Two additional cohorts (labeled Cohort 4 and Cohort 4A) beyond the initial 3 cohorts were actually enrolled in Part 1 of the study.
Following the safety and antiviral activity analyses of the 5 cohorts in Part 1 and the number of subjects enrolled in each of those cohorts, Part 2 of the study was not conducted.
Tipo de estudio
Intervencionista
Inscripción (Actual)
239
Fase
- Fase 2
Contactos y Ubicaciones
Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.
Ubicaciones de estudio
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Alabama
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Birmingham, Alabama, Estados Unidos, 35294
- The University of Alabama at Birmingham
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California
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La Jolla, California, Estados Unidos, 92093
- Moores UCSD Cancer Center
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Los Angeles, California, Estados Unidos, 90095
- UCLA Medical Center
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Colorado
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Aurora, Colorado, Estados Unidos, 80045
- University of Colorado Denver
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Georgia
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Atlanta, Georgia, Estados Unidos, 30322
- Winship Cancer Institute at Emory University
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Illinois
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Chicago, Illinois, Estados Unidos, 60637
- University Of Chicago Medical Center
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Massachusetts
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Boston, Massachusetts, Estados Unidos, 02115
- Brigham and Womens Hospital, Division of Infectious Disease
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Michigan
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Ann Arbor, Michigan, Estados Unidos, 48109
- University of Michigan Medical School
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Detroit, Michigan, Estados Unidos, 48201
- Harper University Hospital
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Minnesota
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Minneapolis, Minnesota, Estados Unidos, 55455
- University of Minnesota Medical Center
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Nebraska
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Omaha, Nebraska, Estados Unidos, 68198-5130
- Nebraska Medical Center
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New Jersey
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Hackensack, New Jersey, Estados Unidos, 07601
- Hackensack University Medical Center
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New York
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Bronx, New York, Estados Unidos, 10467
- Montefiore Medical Center Oncology
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New York, New York, Estados Unidos, 10065
- Memorial Sloan Kettering Cancer Center
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New York, New York, Estados Unidos, 10029
- Mt. Sinai School of Medicine
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Rochester, New York, Estados Unidos, 14642
- University of Rochester Medical Center
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North Carolina
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Chapel Hill, North Carolina, Estados Unidos, 27599
- UNC Health Care Center
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Durham, North Carolina, Estados Unidos, 27710
- Duke University Medical Center
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Winston-Salem, North Carolina, Estados Unidos, 27517
- Wake Forest University School of Medicine
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Ohio
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Cleveland, Ohio, Estados Unidos, 44195
- The Cleveland Clinic
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Oregon
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Portland, Oregon, Estados Unidos, 97239
- Oregon Health and Science University
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Texas
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Dallas, Texas, Estados Unidos, 75246
- Baylor University Medical Center
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Dallas, Texas, Estados Unidos, 75390-8565
- UT Southwestern Medical Center at Dallas
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Houston, Texas, Estados Unidos, 77030
- University of Texas, MD Anderson Cancer Center
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Utah
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Salt Lake City, Utah, Estados Unidos, 84088
- Utah Cancer Specialists - Intermountain Healthcare
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Washington
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Seattle, Washington, Estados Unidos, 98109
- Fred Hutchinson Cancer Research Center
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Criterios de participación
Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.
Criterio de elegibilidad
Edades elegibles para estudiar
18 años y mayores (Adulto, Adulto Mayor)
Acepta Voluntarios Saludables
No
Géneros elegibles para el estudio
Todos
Descripción
Inclusion Criteria
For inclusion into the study, all prospective subjects were required to fulfill all of the following criteria (as applicable):
- Were aged ≥18 years. Males must have been able and willing to use adequate contraceptive methods throughout the treatment and follow-up phases of the study.
- Were cytomegalovirus (CMV) seropositive before allogeneic hematopoietic stem cell transplantation (HCT) (i.e., R+ subjects).
- Were less than 30 days post qualifying transplant.
- Had evidence of engraftment before randomization and receiving their first dose of study drug.
- Were able to ingest and absorb oral medication (in the judgment of the investigator and based on lack of significant gastrointestinal [GI] events).
- Were willing and able to understand and provide written informed consent.
- To the best of his or her knowledge, were willing and able to participate in all required study activities for the duration of the study.
Exclusion Criteria
Subjects meeting any of the following exclusion criteria were to be excluded from participation in the study:
- Females who were pregnant or currently nursing.
- Had a body mass index >35 kg/m2. [Note: This criterion was removed per Protocol Amendment 2 dated 27 August 2010.]
- Had hypersensitivity to cidofovir (CDV) or brincidofovir.
- Recipients for whom the current, predose clinical course of CMV infection suggested that the investigator would not be able to withhold treatment for CMV for a minimum of 5, but preferably 7 days following the subject's first dose of study drug.
Received any of the following:
- Ganciclovir, valganciclovir, foscarnet or CDV within 14 days prior to enrollment;
- Any anti-CMV therapy following transplantation (including Cytogam®1);
- Any CMV vaccine;
- Any investigational drug with antiviral activity against double-stranded DNA (dsDNA) viruses within 14 days prior to enrollment. [Note: An investigational drug was defined as a drug that was not approved for any indication by the Food and Drug Administration.]; or
- Any other investigational drug (i.e., those without any "anti-dsDNA virus" activity; e.g., anti-influenza compounds) within 14 days prior to enrollment without the prior written consent of the medical monitor. The use of investigational drugs in certain circumstances was added per Protocol Amendment 1 dated 15 January 2010.
- Received high dose acyclovir (>2000 mg total oral daily dose or >5 mg/kg intravenously 3 times daily) or valacyclovir (Valtrex; >3000 mg total daily dose) at the time of dosing.
- Were diagnosed with active CMV disease within 6 months prior to enrollment; patients with CMV DNAemia requiring intervention with antiviral therapy at the time of enrollment.
- Were HIV positive; patients with active hepatitis C virus (HCV) or hepatitis B virus (HBV) infection as evidenced by plasma levels of HCV RNA or HBV DNA, respectively.
- Received another allogeneic HCT within the past 2 years, other than the qualifying HCT.
- Had renal insufficiency as evidenced by glomerular filtration rate (GFR) <30 mL/min.
- Had a current diagnosis of hypotony, uveitis, or retinitis or any intraocular pathology that would predispose the subject to any one of these conditions.
- Had hepatic dysfunction as evidenced by alanine aminotransferase or aspartate aminotransferase >5 x the upper limit of normal (ULN) or direct bilirubin >2.5 x the ULN.
- Had any of the following active autoimmune disorders: myasthenia gravis, Addison's disease, Wegener's granulomatosis, primary biliary cirrhosis, bullous pemphigoid, autoimmune hemolytic anemia, autoimmune hepatitis, multiple sclerosis, Goodpasture's syndrome, idiopathic thrombocytopenic purpura, lupus erythematosus, dermatomyositis, polymyositis, or vasculitis.
- Had active solid tumor malignancies with the exception of basal cell carcinoma or the condition under treatment (e.g., lymphomas).
- Had 1 or more episode of hyperglycemic coma or diabetic ketoacidosis within the 6 months prior to enrollment.
- Had cardiovascular disease which, in the opinion of the investigator, would interfere with the conduct of the study.
- Had Grade 3 or 4 graft versus host disease of the GI tract; subjects with any GI disease that would, in the judgment of the investigator, preclude the subject from taking or absorbing oral medication (e.g. clinically active Crohn's disease, ischemic colitis, moderate or severe ulcerative colitis, or any condition expected to require abdominal surgery during the course of study participation).
- Any other condition including abnormal laboratory values that would have, in the judgment of the investigator, put the subject at increased risk for participating in the trial, or interferes with the conduct of the trial.
Plan de estudios
Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Prevención
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación Secuencial
- Enmascaramiento: Doble
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
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Comparador de placebos: Placebo
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Subjects received their first dose of study drug within 30 (+5) days post-transplant and were treated through Week 13 post-transplant. Matching placebo administered for each cohort. |
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Experimental: Brincidofovir
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Subjects received their first dose of study drug of brincidofovir (BCV) within 30 (+5) days post-transplant and were treated through Week 13 post-transplant.
Otros nombres:
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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Number of Participants With Clinically Significant CMV Infection
Periodo de tiempo: Randomization to Week 8 post-treatment (~19 weeks)
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The primary efficacy endpoint was a binomial outcome of failure to prevent cytomegalovirus (CMV) infection defined as CMV DNAemia >200 copies/mL obtained at the time of the last treatment with study drug or diagnosis of CMV disease at some point during the treatment phase.
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Randomization to Week 8 post-treatment (~19 weeks)
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Colaboradores e Investigadores
Aquí es donde encontrará personas y organizaciones involucradas en este estudio.
Patrocinador
Publicaciones y enlaces útiles
La persona responsable de ingresar información sobre el estudio proporciona voluntariamente estas publicaciones. Estos pueden ser sobre cualquier cosa relacionada con el estudio.
Publicaciones Generales
- Lanier ER, Foster S, Brundage T, Chou S, Prichard MN, Kleiboeker S, Wilson C, Colville D, Mommeja-Marin H. Analysis of Mutations in the Gene Encoding Cytomegalovirus DNA Polymerase in a Phase 2 Clinical Trial of Brincidofovir Prophylaxis. J Infect Dis. 2016 Jul 1;214(1):32-5. doi: 10.1093/infdis/jiw073. Epub 2016 Mar 3.
- Marty FM, Winston DJ, Rowley SD, Vance E, Papanicolaou GA, Mullane KM, Brundage TM, Robertson AT, Godkin S, Mommeja-Marin H, Boeckh M; CMX001-201 Clinical Study Group. CMX001 to prevent cytomegalovirus disease in hematopoietic-cell transplantation. N Engl J Med. 2013 Sep 26;369(13):1227-36. doi: 10.1056/NEJMoa1303688.
- Tippin TK, Morrison ME, Brundage TM, Mommeja-Marin H. Brincidofovir Is Not a Substrate for the Human Organic Anion Transporter 1: A Mechanistic Explanation for the Lack of Nephrotoxicity Observed in Clinical Studies. Ther Drug Monit. 2016 Dec;38(6):777-786. doi: 10.1097/FTD.0000000000000353.
Fechas de registro del estudio
Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.
Fechas importantes del estudio
Inicio del estudio (Actual)
1 de octubre de 2009
Finalización primaria (Actual)
1 de enero de 2012
Finalización del estudio (Actual)
1 de enero de 2012
Fechas de registro del estudio
Enviado por primera vez
17 de julio de 2009
Primero enviado que cumplió con los criterios de control de calidad
17 de julio de 2009
Publicado por primera vez (Estimar)
20 de julio de 2009
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
16 de julio de 2021
Última actualización enviada que cumplió con los criterios de control de calidad
28 de junio de 2021
Última verificación
1 de junio de 2021
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
Otros números de identificación del estudio
- CMX001-201
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
No
Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto farmacéutico regulado por la FDA de EE. UU.
Sí
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
No
Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .