Maribavir Versus Oral Ganciclovir For The Prevention of Cytomegalovirus (CMV) Disease in Liver Transplant Recipients

Cytomegalovirus Infections Clinical Trial

Official title:

A Randomized, Double-blind Study To Assess The Efficacy And Safety Of Prophylactic Use Of Maribavir Versus Oral Ganciclovir For The Prevention Of Cytomegalovirus Disease In Recipients Of Orthotopic Liver Transplants

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00497796
• Other study ID #: 1263-301
• Secondary ID: 2007-004729-16SH
• Status: Completed
• Phase: Phase 3
• Start date: July 23, 2007
• Est. completion date: September 14, 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 oral maribavir is safe and effective compared to oral ganciclovir for preventing CMV disease when administered for up to 14 weeks in patients who have had a liver 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 14 weeks following orthotopic liver transplantation.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 307
• Est. completion date: September 14, 2009
• Est. primary completion date: September 14, 2009
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Orthotopic liver transplant recipient

• Donor CMV seropositive / Recipient CMV seronegative

• Enrolled within 10 days after liver transplant

• Able to swallow tablets

Exclusion Criteria:

• Multiple organ transplant

• HIV infection

• CMV disease

• Use of other anti-CMV therapy at time of enrollment

Related Conditions & MeSH terms

• Cytomegalovirus Infections

Intervention

Drug:
• maribavir
100mg twice a day for 14 weeks.
• ganciclovir
1000mg three times per day for 14 weeks.

Locations

Country	Name	City	State
United States	University of Michigan	Ann Arbor	Michigan
United States	Emory University	Atlanta	Georgia
United States	University of Colorado Health Sciences Center	Aurora	Colorado
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	New England Medical Center	Boston	Massachusetts
United States	Lahey Clinic	Burlington	Massachusetts
United States	University of North Carolina, Chapel Hill	Chapel Hill	North Carolina
United States	Medical University of South Carolina	Charleston	South Carolina
United States	University of Virginia Health System	Charlottesville	Virginia
United States	Northwestern University Medical Center	Chicago	Illinois
United States	Rush University Medical Center	Chicago	Illinois
United States	University of Chicago Medical Center	Chicago	Illinois
United States	University of Illinois at Chicago	Chicago	Illinois
United States	University of Cincinnati Medical Center	Cincinnati	Ohio
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	Baylor University Medical Center (Dallas)	Dallas	Texas
United States	Henry Ford Health System	Detroit	Michigan
United States	Duke University Medical Center	Durham	North Carolina
United States	Baylor College of Medicine (Houston)	Houston	Texas
United States	Methodist Hospital	Houston	Texas
United States	UT Memorial Hermann Hospital and Texas Liver Center	Houston	Texas
United States	University of Iowa Hospitals and Clinics	Iowa City	Iowa
United States	Mayo Clinic College of Medicine	Jacksonville	Florida
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	University of California at San Diego	La Jolla	California
United States	University of Kentucky Chandler Medical Center	Lexington	Kentucky
United States	Cedars-Sinai Medical Center	Los Angeles	California
United States	UCLA Medical Center	Los Angeles	California
United States	Jewish Hospital Louisville	Louisville	Kentucky
United States	Methodist Transplant Institute	Memphis	Tennessee
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	University of Minnesota	Minneapolis	Minnesota
United States	Ochsner Clinic	New Orleans	Louisiana
United States	Tulane University Hospital and Clinic	New Orleans	Louisiana
United States	Columbia University Medical Center	New York	New York
United States	NYU School of Medicine	New York	New York
United States	University of Medicine and Dentistry of New Jersey	Newark	New Jersey
United States	Integris Baptist Medical Center	Oklahoma City	Oklahoma
United States	University of Nebraska	Omaha	Nebraska
United States	University of Pennsylvania Hospital	Philadelphia	Pennsylvania
United States	Mayo Clinic Arizona	Phoenix	Arizona
United States	VA Pittsburgh Healthcare System	Pittsburgh	Pennsylvania
United States	Oregon Health and Sciences University	Portland	Oregon
United States	Virginia Commonwealth University	Richmond	Virginia
United States	Mayo Clinic Rochester	Rochester	Minnesota
United States	University of Rochester Medical Center- Strong Memorial	Rochester	New York
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	University of Texas Health Sciences Center at San Antonio	San Antonio	Texas
United States	University of California at San Francisco	San Francisco	California
United States	Univeristy of Washington Medical Center	Seattle	Washington
United States	Stanford University Medical Center	Stanford	California
United States	Tampa General	Tampa	Florida
United States	New York Medical College	Valhalla	New York
United States	Georgetown University	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Shire

Country where clinical trial is conducted

United States, 

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 (protocol-defined) cases of CMV disease (i.e., symptomatic CMV infection or CMV organ disease), were adjudicated by an independent, blinded EC. Symptomatic 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 polymerase chain reaction [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-Transplantation	Incidence of CMV infection or EC-confirmed CMV disease within the 6-month post-transplant period included in this section were defined (1) with infection assessed by pp65 antigenemia assay; (2) with infection assessed by CMV DNA PCR; (3) with infection assessed by either assay (pp65 antigenemia or CMV DNA PCR); and (4) with infection assessed by initiation of anti-CMV therapy.	6 months post-transplant
Secondary	Time to Onset of CMV Infection or EC-confirmed CMV Disease Within 6 Months Post-Transplantation	All investigator-determined (protocol-defined) cases of CMV disease (i.e., symptomatic CMV infection or CMV organ disease) were adjudicated by an independent, blinded EC. CMV infection was assessed by pp65 Antigenemia or CMV DNA PCR from a central or local lab. 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	Symptomatic 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 polymerase chain reaction [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 6 months post-transplant (Day 1 to 100 days and 6 months post-transplant)
Secondary	Number of Participants With EC-confirmed CMV Disease Within 100 Days Post-Transplantation	All investigator-determined (protocol-defined) cases of CMV disease (i.e., symptomatic CMV infection or CMV organ disease), were adjudicated by an independent, blinded EC. Symptomatic 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 polymerase chain reaction [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 CMV Infection or EC-confirmed CMV Disease Within 100 Days Post-Transplantation	Incidence of CMV infection or EC-confirmed CMV disease within the 6-month post-transplant period included in this section were defined (1) with infection assessed by pp65 antigenemia assay; (2) with infection assessed by CMV DNA PCR; (3) with infection assessed by either assay (pp65 antigenemia or CMV DNA PCR); and (4) with infection assessed by initiation of anti-CMV therapy.	100 days post-transplant
Secondary	Number of Participants With Retransplantation		Through 6 months post-transplant (From Day 1 to 100 days and 6 months post-transplant)
Secondary	Number of Participants With Graft Failure Related Death		Through 6 months post-transplant (From Day 1 to 100 days and 6 months post-transplant)
Secondary	Number of Participants With Acute Graft Rejection	Rejection was assessed by examining a liver biopsy sample. Diagnosis of graft rejection included a global assessment grade and a rejection activity index score.	26 weeks post-transplant
Secondary	Number of Participants Who Died Within 6 Months Post-Transplantation		6 months post-transplant
Secondary	Percent of Participants With Signs of Bone Marrow Suppression	Bone marrow suppression was assessed by the occurrence of adverse events (AEs) of investigator-reported leukopenia, neutropenia, thrombocytopenia, and pancytopenia; absolute neutrophil count (ANC) <1000/mm3; white blood cell (WBC) count toxicity grade shifts from 0-2 at baseline to a maximum of 3-4 post-baseline; and use of hematopoietic growth factors during the 6 month post-transplant period.	15 weeks
Secondary	Plasma Concentration of Maribavir During Treatment	For the first 16 subjects to have PK profiling performed, PK sampling was collected at Weeks 2, 6 and 10. For subsequent subjects that have PK profiling performed, PK sampling was collected at Weeks 2 and 6. Samples were collected 12 hours after the morning dose of maribavir. Permissible assessment windows for pharmacokinetic profile sampling purposes were +/- 5 days for each sampling day. Samples for determination of maribavir concentration were analyzed by a validated liquid chromatography tandem mass spectrometry (LC/MS/MS) method. For plasma, the minimum detectable concentration for maribavir was 0.2 µg/mL.	12 hours post-dose after 2, 6, and 10 weeks of treatment
Secondary	Plasma Concentration of Maribavir Metabolite VP 44469 During Treatment	For the first 16 subjects to have PK profiling performed, PK sampling was collected at Weeks 2, 6 and 10. For subsequent subjects that have PK profiling performed, PK sampling was collected at Weeks 2 and 6. Samples were collected 12 hours after the morning dose of maribavir. Permissible assessment windows for pharmacokinetic profile sampling purposes were +/- 5 days for each sampling day. Samples for determination of VP 44469 (a metabolite of maribavir) concentration were analyzed by a validated liquid chromatography tandem mass spectrometry (LC/MS/MS) method. For plasma, the minimum detectable concentration for VP 44469 was 0.2 µg/mL.	12 hours post-dose after 2, 6, and 10 weeks of treatment