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

Cytomegalovirus Infections Clinical Trial

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00411645
• Other study ID #: 1263-300
• Secondary ID: 2006-005692-18SH
• Status: Completed
• Phase: Phase 3
• Start date: December 13, 2006
• Est. completion date: May 23, 2009

Study information

• Verified date: June 2021
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Other known NCT identifiers

• NCT00430339

Recruitment information / eligibility

• Status: Completed
• Enrollment: 681
• Est. completion date: May 23, 2009
• Est. primary completion date: November 10, 2008
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cytomegalovirus Infections

Intervention

Drug:
• maribavir
100 mg twice daily for up to 12 weeks

Other:
• placebo
twice daily for up to 12 weeks

Locations

Country	Name	City	State
Belgium	ZNA Stuivenberg	Antwerp
Belgium	AZ Sint Jan, Department of Hematology	Brugge
Belgium	Cliniques Universitaires St,Luc Dept Hematology	Brussels
Belgium	UZ Gasthuisberg	Leuven
Belgium	CHU Sart -Tilman Department of Medicine, Hematology	Liege
Canada	QEII Health Sciences Center	Halifax	Nova Scotia
Canada	McMaster University Medical Center	Hamilton	Ontario
Canada	London Health Sciences Centre	London	Ontario
Canada	Ottawa General Campus	Ottawa,	Ontario
Canada	Hopital l'Enfant Jesus	Quebec
France	Hopital Henri Mondor	Créteil
France	Edouard Herriot Hopital	Lyon, Cedex 03
France	Institut Paoli Calmettes	Marseille Cedex 9
France	Hopital Hotel Dieu	Nantes, Cedex 1
France	Hopital St. Louis	Paris Cedex 10
France	Hopital Haut-Leveque	Pessac
Germany	Univ. Clinic Dresden	Dresden
Germany	University Clinic of Dresden	Dresden
Germany	University of Essen	Essen
Germany	University of Freiburg	Freiburg
Germany	University of Hamburg-Eppendorf	Hamburg
Germany	Hannover, Medizinische Hochschule	Hannover
Germany	University of Heidelberg	Heidelberg
Germany	Universitaetsklinikum Koeln, Clinic I for internal Medicine	Koeln
Germany	Johannes-Gutenberg University	Mainz
Germany	University Clinic of Ulm	Ulm
Italy	Careggi University Hospital	Firenze
Italy	University of San Martino Hospital	Genova
Italy	San Raffaele del Monte Tabor	Milano
Italy	Pescara Hospital	Pescara
Italy	Bianchi-Melacrino-Morelli Hospital	Reggio Calabria
Spain	Barcelona Hospital	Barcelona
Spain	Duran i Reynals Hospital	Barcelona
Spain	University of Salamanca	Salamanca
Sweden	Sahlgrenska University Hospital	Goteborg
Sweden	Karolinska University Hospital	Huddinge	Stockholm
Sweden	Karolinska University Hospital,Huddinge	Stockholm
Sweden	Akademiska Sjukhuset, Dept Hematology	Uppsala
United Kingdom	Hammersmith Hospital	London
United Kingdom	Royal Free Hospital	London
United Kingdom	University College Hospital	London
United States	University of Michigan	Ann Arbor	Michigan
United States	Emory University	Atlanta	Georgia
United States	Greenbaum Cancer Center	Baltimore	Maryland
United States	St Francis Hospital	Beech Grove	Indiana
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	Massachusettes General	Boston	Massachusetts
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	University of North Carolina Hospital	Chapel Hill	North Carolina
United States	Northwestern University Medical Center	Chicago	Illinois
United States	University of Chicago	Chicago	Illinois
United States	The Jewish Hospital	Cincinnati	Ohio
United States	Ireland Cancer Center Case Western Reserve University	Cleveland	Ohio
United States	Baylor University Medical Center	Dallas	Texas
United States	Rocky Mountain Cancer Center	Denver	Colorado
United States	Henry Ford Health System	Detroit	Michigan
United States	Wayne State Medical Center	Detroit	Michigan
United States	City of Hope Medical Center	Duarte	California
United States	Duke Medical Center	Durham	North Carolina
United States	Shands Hospital	Gainesville	Florida
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	Penn State Milton S. Hershey Medical Center	Hershey	Pennsylvania
United States	MD Anderson Cancer Center	Houston	Texas
United States	Methodist Hospital	Houston	Texas
United States	University of Iowa Hospitals and Clinics	Iowa City	Iowa
United States	Scripps Green Hospital	La Jolla	California
United States	UCSD Moores Center	La Jolla	California
United States	University of Kentucky Chandler Medical Center	Lexington	Kentucky
United States	University of Arkansas Myeloma Institute	Little Rock	Arkansas
United States	UCLA Medical Center	Los Angeles	California
United States	University Medical Center University of Louisville Hospital	Louisville	Kentucky
United States	Loyola University	Maywood	Illinois
United States	University of Minnesota	Minneapolis	Minnesota
United States	West Virginia University Hospital	Morgantown	West Virginia
United States	Vanderbilt Medical Center	Nashville	Tennessee
United States	Memorial Sloan-Kettering Cancer Center	New York	New York
United States	Mount Sinai Hospital	New York	New York
United States	New York Presbyterian Hospital,Weill Cornell Medical Center	New York	New York
United States	University of Oklahoma	Oklahoma City	Oklahoma
United States	Jeanes Hospital - Temple	Philadelphia	Pennsylvania
United States	Thomas Jefferson	Philadelphia	Pennsylvania
United States	University of Pittsburgh Cancer Institute	Pittsburgh	Pennsylvania
United States	Western Pennsylvania Cancer Institute	Pittsburgh	Pennsylvania
United States	Oregon Health and Sciences University	Portland	Oregon
United States	Medical College of Virginia	Richmond	Virginia
United States	Mayo Clinic College of Medicine	Rochester	Minnesota
United States	University of Rochester Medical Center	Rochester	New York
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Latter Day Saints Hospital	Salt Lake City	Utah
United States	Texas Transplant Institute	San Antonio	Texas
United States	University of California, San Francisco	San Francisco	California
United States	Fred Hutchinson Cancer Research Center	Seattle	Washington
United States	VA Puget Sound Health Center	Seattle	Washington
United States	Stanford University Medical Center	Stanford	California
United States	H. Lee Moffitt Cancer Center	Tampa	Florida
United States	Wake Forest Medical Center	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Shire

Countries where clinical trial is conducted

United States,  Belgium,  Canada,  France,  Germany,  Italy,  Spain,  Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Endpoint Committee (EC)-Confirmed Cytomegalovirus (CMV) Disease Within 6 Months Post-Transplantation	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.	6 months post-transplant
Secondary	Number of Participants With CMV Infection or EC-confirmed CMV Disease Within 6 Months Post-transplant	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.	6 months post-transplant
Secondary	Time to Onset of CMV Infection or EC-confirmed CMV Disease Within 6 Months Post- Transplantation	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.	6 months post-transplant
Secondary	Number of Participants With Investigator-determined CMV Disease	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.	Through 12 months post-transplant (Day 1 to 100 days, 6 months, and 12 months post-transplant)
Secondary	Number of Participants With CMV Infection or EC-confirmed CMV Disease Within 100 Days Post-Transplantation	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.	100 days post-transplant
Secondary	Number of Participants With EC-confirmed CMV Disease Within 12 Months Post-Transplantation	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.	12 months post-transplant
Secondary	Percent of Participants With Acute Graft-Versus-Host Disease (GVHD)	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.	Through 6 months post-transplant (Days 1 to 100 and 6 months post-transplant)
Secondary	Percent of Participants With Chronic Graft-Versus-Host Disease (GVHD)	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.	Through 6 months post-transplant (Days 1 to 100 and 6 months post-transplant)
Secondary	Number of Participants Who Died Within 12 Months Post-Transplantation		Through 12 months post-transplant (Days 1 to 100, 6 months, and 12 months post-transplant)
Secondary	Plasma Concentration of Maribavir During Treatment	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.	12 hours post-dose after 1 and 4 weeks of treatment
Secondary	Plasma Concentration of Maribavir Metabolite VP 44469 During Treatment	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.	12 hours post-dose after 1 and 4 weeks of treatment