Prophylactic Use of Maribavir for the Prevention of Cytomegalovirus (CMV) Disease in Stem Cell Transplant Recipients

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Shire
ClinicalTrials.gov Identifier:
NCT00411645
First received: December 12, 2006
Last updated: June 3, 2015
Last verified: March 2014
  Purpose

The purpose of this research study is to investigate whether or not maribavir is safe and effective for preventing CMV disease when taken by mouth for up to 12 weeks in patients who have had a stem cell transplant.


Condition Intervention Phase
Cytomegalovirus Infections
Drug: maribavir
Other: placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Prevention
Official Title: A Randomized, Double-blind, Placebo-controlled Study to Assess the Efficacy and Safety of Prophylactic Use of Maribavir for the Prevention of Cytomegalovirus Disease in Recipients of Allogeneic Stem Cell Transplants.

Resource links provided by NLM:


Further study details as provided by Shire:

Primary Outcome Measures:
  • Number of Participants With Endpoint Committee (EC)-Confirmed Cytomegalovirus (CMV) Disease Within 6 Months Post-Transplantation [ Time Frame: 6 months post-transplant ] [ Designated as safety issue: No ]
    All investigator-determined cases of CMV disease (i.e., CMV infection or CMV organ disease), were adjudicated by an independent, blinded EC. CMV infection was assessed by (1) pp65 antigenemia assay; (2) CMV DNA polymerase chain reaction (PCR); (3) either assay (pp65 antigenemia or CMV DNA PCR); or (4) initiation of anti-CMV therapy. CMV infection was defined as: CMV infection detected by a positive result from a CMV laboratory assay from at least one central laboratory assay (pp65 antigenemia or CMV DNA PCR assay in plasma) and fever >/=38 °C on >/=2 occasions >/=24 hours apart within a 7-day period and at least one of the following: new or increased malaise, two successive measurements of leucopenia (white blood cell [WBC] count <3500/mm3 or a WBC count decrease of 20% if the cell count prior to onset of clinical symptoms was >4000/mm3) >/=24 hours apart, atypical lymphocytosis >/=5%, and thrombocytopenia. CMV organ disease was defined as described by Ljungman et al., 2002.


Secondary Outcome Measures:
  • Number of Participants With CMV Infection or EC-confirmed CMV Disease Within 6 Months Post-transplant [ Time Frame: 6 months post-transplant ] [ Designated as safety issue: No ]
    All investigator-determined cases of CMV disease (i.e., CMV infection or CMV organ disease), were adjudicated by an independent, blinded EC. CMV infection was assessed by (1) pp65 antigenemia assay; (2) CMV DNA polymerase chain reaction (PCR); (3) either assay (pp65 antigenemia or CMV DNA PCR); or (4) initiation of anti-CMV therapy. CMV infection was defined as: CMV infection detected by a positive result from a CMV laboratory assay from at least one central laboratory assay (pp65 antigenemia or CMV DNA PCR assay in plasma) and fever >/=38 °C on >/=2 occasions >/=24 hours apart within a 7-day period and at least one of the following: new or increased malaise, two successive measurements of leucopenia (white blood cell [WBC] count <3500/mm3 or a WBC count decrease of 20% if the cell count prior to onset of clinical symptoms was >4000/mm3) >/=24 hours apart, atypical lymphocytosis >/=5%, and thrombocytopenia. CMV organ disease was defined as described by Ljungman et al., 2002.

  • Time to Onset of CMV Infection or EC-confirmed CMV Disease Within 6 Months Post- Transplantation [ Time Frame: 6 months post-transplant ] [ Designated as safety issue: No ]
    All investigator-determined cases of CMV disease (i.e., CMV infection or CMV organ disease) were adjudicated by an independent, blinded EC. CMV infection was assessed by (1) pp65 antigenemia assay or (2) CMV DNA polymerase chain reaction (PCR). CMV infection was defined as: CMV infection detected by a positive result from a CMV laboratory assay from at least one central laboratory assay (pp65 antigenemia or CMV DNA PCR assay in plasma) and fever >/=38 °C on >/=2 occasions >/=24 hours apart within a 7-day period and at least one of the following: new or increased malaise, two successive measurements of leucopenia (white blood cell [WBC] count <3500/mm3 or a WBC count decrease of 20% if the cell count prior to onset of clinical symptoms was >4000/mm3) >/=24 hours apart, atypical lymphocytosis >/=5%, and thrombocytopenia. CMV organ disease was defined as described by Ljungman et al., 2002.

  • Number of Participants With Investigator-determined CMV Disease [ Time Frame: Through 12 months post-transplant (Day 1 to 100 days, 6 months, and 12 months post-transplant) ] [ Designated as safety issue: No ]
    CMV infection was assessed by (1) pp65 antigenemia assay; (2) CMV DNA polymerase chain reaction (PCR); (3) either assay (pp65 antigenemia or CMV DNA PCR); or (4) initiation of anti-CMV therapy. CMV infection was defined as: CMV infection detected by a positive result from a CMV laboratory assay from at least one central laboratory assay (pp65 antigenemia or CMV DNA PCR assay in plasma) and fever >/=38 °C on >/=2 occasions >/=24 hours apart within a 7-day period and at least one of the following: new or increased malaise, two successive measurements of leucopenia (white blood cell [WBC] count <3500/mm3 or a WBC count decrease of 20% if the cell count prior to onset of clinical symptoms was >4000/mm3) >/=24 hours apart, atypical lymphocytosis >/=5%, and thrombocytopenia. CMV organ disease was defined as described by Ljungman et al., 2002.

  • Number of Participants With CMV Infection or EC-confirmed CMV Disease Within 100 Days Post-Transplantation [ Time Frame: 100 days post-transplant ] [ Designated as safety issue: No ]
    All investigator-determined cases of CMV disease (i.e., CMV infection or CMV organ disease), were adjudicated by an independent, blinded EC. CMV infection was assessed by (1) pp65 antigenemia assay; (2) CMV DNA polymerase chain reaction (PCR); (3) either assay (pp65 antigenemia or CMV DNA PCR); or (4) initiation of anti-CMV therapy. CMV infection was defined as: CMV infection detected by a positive result from a CMV laboratory assay from at least one central laboratory assay (pp65 antigenemia or CMV DNA PCR assay in plasma) and fever >/=38 °C on >/=2 occasions >/=24 hours apart within a 7-day period and at least one of the following: new or increased malaise, two successive measurements of leucopenia (white blood cell [WBC] count <3500/mm3 or a WBC count decrease of 20% if the cell count prior to onset of clinical symptoms was >4000/mm3) >/=24 hours apart, atypical lymphocytosis >/=5%, and thrombocytopenia. CMV organ disease was defined as described by Ljungman et al., 2002.

  • Number of Participants With EC-confirmed CMV Disease Within 12 Months Post-Transplantation [ Time Frame: 12 months post-transplant ] [ Designated as safety issue: No ]
    All investigator-determined cases of CMV disease (i.e., CMV infection or CMV organ disease), were adjudicated by an independent, blinded EC. CMV infection was assessed by (1) pp65 antigenemia assay; (2) CMV DNA polymerase chain reaction (PCR); (3) either assay (pp65 antigenemia or CMV DNA PCR); or (4) initiation of anti-CMV therapy. CMV infection was defined as: CMV infection detected by a positive result from a CMV laboratory assay from at least one central laboratory assay (pp65 antigenemia or CMV DNA PCR assay in plasma) and fever >/=38 °C on >/=2 occasions >/=24 hours apart within a 7-day period and at least one of the following: new or increased malaise, two successive measurements of leucopenia (white blood cell [WBC] count <3500/mm3 or a WBC count decrease of 20% if the cell count prior to onset of clinical symptoms was >4000/mm3) >/=24 hours apart, atypical lymphocytosis >/=5%, and thrombocytopenia. CMV organ disease was defined as described by Ljungman et al., 2002.

  • Percent of Participants With Acute Graft-Versus-Host Disease (GVHD) [ Time Frame: Through 6 months post-transplant (Days 1 to 100 and 6 months post-transplant) ] [ Designated as safety issue: No ]
    Analysis of acute GVHD was based on reported adverse events that mapped to the relevant MedDRA dictionary terms for acute GVHD. The percentage reported is for the occurrence of any grade of acute GVHD.

  • Percent of Participants With Chronic Graft-Versus-Host Disease (GVHD) [ Time Frame: Through 6 months post-transplant (Days 1 to 100 and 6 months post-transplant) ] [ Designated as safety issue: No ]
    Analysis of chronic GVHD was based on reported adverse events that mapped to the relevant MedDRA dictionary terms for chronic GVHD. The percentage reported is for the occurrence of any grade of chronic GVHD.

  • Number of Participants Who Died Within 12 Months Post-Transplantation [ Time Frame: Through 12 months post-transplant (Days 1 to 100, 6 months, and 12 months post-transplant) ] [ Designated as safety issue: No ]
  • Plasma Concentration of Maribavir During Treatment [ Time Frame: 12 hours post-dose after 1 and 4 weeks of treatment ] [ Designated as safety issue: No ]
    Pharmacokinetic (PK) profile sampling was performed to evaluate plasma concentrations of Maribavir. During the study drug administration period, blood samples for this purpose were collected on Day 7 (Week 1) and at Week 4. Every effort was made to ensure that doses were administered 12 hours apart on the day before and on the day of PK sampling. Permissible assessment windows for PK profile sampling purposes were +/- 3 days and +/- 5 days for the 1- and 4- week samples, respectively. Samples were analyzed by a validated liquid chromatography tandem mass spectrometry (LC/MS/MS) method. The validated lower limit of quantitation (LLOQ) in plasma was 0.2 μg/mL.

  • Plasma Concentration of Maribavir Metabolite VP 44469 During Treatment [ Time Frame: 12 hours post-dose after 1 and 4 weeks of treatment ] [ Designated as safety issue: No ]
    Pharmacokinetic (PK) profile sampling was performed to evaluate plasma concentrations of VP 44469, a metabolite of Maribavir. During the study drug administration period, blood samples for this purpose were collected on Day 7 (Week 1) and at Week 4. Every effort was made to ensure that doses were administered 12 hours apart on the day before and on the day of PK sampling. Permissible assessment windows for PK profile sampling purposes were +/- 3 days and +/- 5 days for the 1- and 4- week samples, respectively. Samples were analyzed by a validated liquid chromatography tandem mass spectrometry (LC/MS/MS) method. The validated lower limit of quantitation (LLOQ) in plasma was 0.2 μg/mL.


Enrollment: 681
Study Start Date: December 2006
Study Completion Date: May 2009
Primary Completion Date: November 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A Drug: maribavir
100 mg twice daily for up to 12 weeks
Placebo Comparator: B Other: placebo
twice daily for up to 12 weeks

Detailed Description:

Cytomegalovirus (CMV) infections remain a significant problem following various types of transplants that are associated with strong immunosuppressive therapy. Maribavir is a new oral anti-CMV drug with a novel mechanism of action compared to currently available anti-CMV drugs. This study will test the safety and efficacy of maribavir for the prevention of CMV disease when given as prophylaxis for up to 12 weeks following allogeneic stem cell transplant.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Allogeneic stem cell transplant recipient
  • Recipient or donor CMV seropositive
  • Have transplant engraftment
  • Able to swallow tablets

Exclusion Criteria:

  • CMV organ disease
  • HIV infection
  • Use of other anti-CMV therapy post-transplant
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00411645

  Hide Study Locations
Locations
United States, Arkansas
University of Arkansas Myeloma Institute
Little Rock, Arkansas, United States, 72205
United States, California
City of Hope Medical Center
Duarte, California, United States, 91010
Scripps Green Hospital
La Jolla, California, United States, 92037
UCSD Moores Center
La Jolla, California, United States, 92093-0960
UCLA Medical Center
Los Angeles, California, United States, 90095-1678
University of California, San Francisco
San Francisco, California, United States, 94143
Stanford University Medical Center
Stanford, California, United States, 94305
United States, Colorado
Rocky Mountain Cancer Center
Denver, Colorado, United States, 80218
United States, Florida
Shands Hospital
Gainsville, Florida, United States, 32610
H. Lee Moffitt Cancer Center
Tampa, Florida, United States, 33612
United States, Georgia
Emory University
Atlanta, Georgia, United States, 30322
United States, Illinois
Northwestern University Medical Center
Chicago, Illinois, United States, 60611
University of Chicago
Chicago, Illinois, United States, 60637
Loyola University
Maywood, Illinois, United States, 60153
United States, Indiana
St Francis Hospital
Beech Grove, Indiana, United States, 46107
United States, Iowa
University of Iowa Hospitals and Clinics
Iowa City, Iowa, United States, 52242
United States, Kentucky
University of Kentucky Chandler Medical Center
Lexington, Kentucky, United States, 40536
University Medical Center University of Louisville Hospital
Louisville, Kentucky, United States, 40202
United States, Maryland
Greenbaum Cancer Center
Baltimore, Maryland, United States, 21201-1595
United States, Massachusetts
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02215
Brigham and Women's Hospital
Boston, Massachusetts, United States, 02115
Massachusettes General
Boston, Massachusetts, United States, 02114
United States, Michigan
University of Michigan
Ann Arbor, Michigan, United States, 48109-0914
Henry Ford Health System
Detroit, Michigan, United States, 48202
Wayne State Medical Center
Detroit, Michigan, United States, 48201
United States, Minnesota
University of Minnesota
Minneapolis, Minnesota, United States, 55455
Mayo Clinic College of Medicine
Rochester, Minnesota, United States, 55905
United States, Missouri
Washington University School of Medicine
St. Louis, Missouri, United States, 63110
United States, New Jersey
Hackensack University Medical Center
Hackensack, New Jersey, United States, 07601
United States, New York
Roswell Park Cancer Institute
Buffalo, New York, United States, 14263
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10021
Mount Sinai Hospital
New York, New York, United States, 10029
New York Presbyterian Hospital,Weill Cornell Medical Center
New York, New York, United States, 10021
University of Rochester Medical Center
Rochester, New York, United States, 14642
United States, North Carolina
University of North Carolina Hospital
Chapel Hill, North Carolina, United States, 27599
Duke Medical Center
Durham, North Carolina, United States, 27710
Wake Forest Medical Center
Winston-Salem, North Carolina, United States, 27157
United States, Ohio
The Jewish Hospital
Cincinnati, Ohio, United States, 45236
Ireland Cancer Center Case Western Reserve University
Cleveland, Ohio, United States, 44106
United States, Oklahoma
University of Oklahoma
Oklahoma City, Oklahoma, United States, 73104
United States, Oregon
Oregon Health and Sciences University
Portland, Oregon, United States, 97239-3098
United States, Pennsylvania
Penn State Milton S. Hershey Medical Center
Hershey, Pennsylvania, United States, 17033
Jeanes Hospital - Temple
Philadelphia, Pennsylvania, United States, 19111
Thomas Jefferson
Philadelphia, Pennsylvania, United States, 19107
University of Pittsburgh Cancer Institute
Pittsburgh, Pennsylvania, United States, 15232
Western Pennsylvania Cancer Institute
Pittsburgh, Pennsylvania, United States, 15224
United States, Tennessee
Vanderbilt Medical Center
Nashville, Tennessee, United States, 37232
United States, Texas
Baylor University Medical Center
Dallas, Texas, United States, 75246
MD Anderson Cancer Center
Houston, Texas, United States, 77030-4009
Methodist Hospital
Houston, Texas, United States, 77030
Texas Transplant Institute
San Antonio, Texas, United States, 78229
United States, Utah
Latter Day Saints Hospital
Salt Lake City, Utah, United States, 84103
United States, Virginia
Medical College of Virginia
Richmond, Virginia, United States, 23298
United States, Washington
Fred Hutchinson Cancer Research Center
Seattle, Washington, United States, 98109
VA Puget Sound Health Center
Seattle, Washington, United States, 98108
United States, West Virginia
West Virginia University Hospital
Morgantown, West Virginia, United States, 26506-9162
Belgium
ZNA Stuivenberg
Antwerp, Belgium, 2060
AZ Sint Jan, Department of Hematology
Brugge, Belgium, 8000
Cliniques Universitaires St,Luc Dept Hematology
Brussels, Belgium, 1200
UZ Gasthuisberg
Leuven, Belgium, 3000
CHU Sart -Tilman Department of Medicine, Hematology
Liege, Belgium, 4000
Canada, Nova Scotia
QEII Health Sciences Center
Halifax, Nova Scotia, Canada, B3H2Y9
Canada, Ontario
McMaster University Medical Center
Hamilton, Ontario, Canada, L8N 3Z5
London Health Sciences Centre
London, Ontario, Canada, N6A 4G5
Ottawa General Campus
Ottawa,, Ontario, Canada, K1H 8L6
Canada
Hopital l'Enfant Jesus
Quebec, Canada, G1J 1Z4
France
Hopital Henri Mondor
Créteil, France, 94010
Edouard Herriot Hopital
Lyon, Cedex 03, France, 69437
Institut Paoli Calmettes
Marseille Cedex 9, France, 13273
Hopital Hotel Dieu
Nantes, Cedex 1, France, 44093
Hopital St. Louis
Paris Cedex 10, France, 75475
Hopital Haut-Leveque
Pessac, France, 33600
Germany
Univ. Clinic Dresden
Dresden, Germany, 01307
University Clinic of Dresden
Dresden, Germany, 01307
University of Essen
Essen, Germany, 45122
University of Freiburg
Freiburg, Germany, 79106
University of Hamburg-Eppendorf
Hamburg, Germany, 20246
Hannover, Medizinische Hochschule
Hannover, Germany, 30625
University of Heidelberg
Heidelberg, Germany, 69120
Universitaetsklinikum Koeln, Clinic I for internal Medicine
Koeln, Germany, 50937
Johannes-Gutenberg University
Mainz, Germany, 55131
University Clinic of Ulm
Ulm, Germany, 89081
Italy
Careggi University Hospital
Firenze, Italy, 50134
University of San Martino Hospital
Genova, Italy, 16132
San Raffaele del Monte Tabor
Milano, Italy, 20132
Pescara Hospital
Pescara, Italy, 65123
Bianchi-Melacrino-Morelli Hospital
Reggio Calabria, Italy, 89100
Spain
Duran i Reynals Hospital
Barcelona, Spain, 08907
Barcelona Hospital
Barcelona, Spain, 08036
University of Salamanca
Salamanca, Spain, E-37007
Sweden
Karolinska University Hospital
Huddinge, Stockholm, Sweden, 14186
Sahlgrenska University Hospital
Goteborg, Sweden, S-413 45
Karolinska University Hospital,Huddinge
Stockholm, Sweden, 141 86
Akademiska Sjukhuset, Dept Hematology
Uppsala, Sweden, 751 85
United Kingdom
Hammersmith Hospital
London, United Kingdom, W12 OHS
Royal Free Hospital
London, United Kingdom, NW3 2QG
University College Hospital
London, United Kingdom, NW1 2BU
Sponsors and Collaborators
Shire
Investigators
Study Director: Stephen A Villano, MD ViroPharma
  More Information

No publications provided by Shire

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Shire
ClinicalTrials.gov Identifier: NCT00411645     History of Changes
Obsolete Identifiers: NCT00430339
Other Study ID Numbers: 1263-300, 2006-005692-18, SHP620-300
Study First Received: December 12, 2006
Results First Received: May 15, 2015
Last Updated: June 3, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by Shire:
prevention
prophylaxis
Cytomegalovirus
CMV
allogeneic stem cell transplant
SCT

Additional relevant MeSH terms:
Cytomegalovirus Infections
DNA Virus Infections
Herpesviridae Infections
Virus Diseases

ClinicalTrials.gov processed this record on July 28, 2015