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

Phase 3

Completed

Conditions: Cytomegalovirus Infections

Interventions: Other: placebo
Drug: maribavir

Registration Number: NCT00411645

Lead Sponsor: Shire

Brief 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.

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 681

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
B	placebo	-
A	maribavir	-

Primary Outcome Measures

Name	Time	Method
Number of Participants With Endpoint Committee (EC)-Confirmed Cytomegalovirus (CMV) Disease Within 6 Months Post-Transplantation	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.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With CMV Infection or EC-confirmed CMV Disease Within 6 Months Post-transplant	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.
Percent of Participants With Acute Graft-Versus-Host Disease (GVHD)	Through 6 months post-transplant (Days 1 to 100 and 6 months post-transplant)	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)	Through 6 months post-transplant (Days 1 to 100 and 6 months post-transplant)	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.
Plasma Concentration of Maribavir During Treatment	12 hours post-dose after 1 and 4 weeks of 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.
Number of Participants With CMV Infection or EC-confirmed CMV Disease Within 100 Days Post-Transplantation	100 days 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.
Plasma Concentration of Maribavir Metabolite VP 44469 During Treatment	12 hours post-dose after 1 and 4 weeks of 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.
Time to Onset of CMV Infection or EC-confirmed CMV Disease Within 6 Months Post- Transplantation	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 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	Through 12 months post-transplant (Day 1 to 100 days, 6 months, and 12 months post-transplant)	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	12 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.
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)

Trial Locations

Locations (97): University of Arkansas Myeloma Institute
🇺🇸
Little Rock, Arkansas, United States
City of Hope Medical Center
🇺🇸
Duarte, California, United States
Scripps Green Hospital
🇺🇸
La Jolla, California, United States
UCSD Moores Center
🇺🇸
La Jolla, California, United States
UCLA Medical Center
🇺🇸
Los Angeles, California, United States
University of California, San Francisco
🇺🇸
San Francisco, California, United States
Stanford University Medical Center
🇺🇸
Stanford, California, United States
Rocky Mountain Cancer Center
🇺🇸
Denver, Colorado, United States
Shands Hospital
🇺🇸
Gainesville, Florida, United States
H. Lee Moffitt Cancer Center
🇺🇸
Tampa, Florida, United States
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University of Arkansas Myeloma Institute
🇺🇸Little Rock, Arkansas, United States