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

June 2, 2021 updated by: Shire

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 14 weeks following orthotopic liver transplantation.

Study Type

Interventional

Enrollment (Actual)

307

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Arizona
      • Phoenix, Arizona, United States, 85006
        • Mayo Clinic Arizona
    • California
      • La Jolla, California, United States, 92103
        • University of California at San Diego
      • Los Angeles, California, United States, 90048
        • Cedars-Sinai Medical Center
      • Los Angeles, California, United States, 90095
        • UCLA Medical Center
      • San Francisco, California, United States, 94143
        • University of California at San Francisco
      • Stanford, California, United States, 94305
        • Stanford University Medical Center
    • Colorado
      • Aurora, Colorado, United States, 80045
        • University of Colorado Health Sciences Center
    • District of Columbia
      • Washington, District of Columbia, United States, 20007
        • Georgetown University
    • Florida
      • Jacksonville, Florida, United States, 32224
        • Mayo Clinic College of Medicine
      • Tampa, Florida, United States, 33606
        • Tampa General
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Emory University
    • Illinois
      • Chicago, Illinois, United States, 60612
        • University of Illinois at Chicago
      • Chicago, Illinois, United States, 60612
        • Rush University Medical Center
      • Chicago, Illinois, United States, 60637
        • University Of Chicago Medical Center
      • Chicago, Illinois, United States, 60611
        • Northwestern University Medical Center
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • University of Iowa Hospitals and Clinics
    • Kansas
      • Kansas City, Kansas, United States, 66160
        • University of Kansas Medical Center
    • Kentucky
      • Lexington, Kentucky, United States, 40536
        • University of Kentucky Chandler Medical Center
      • Louisville, Kentucky, United States, 40202
        • Jewish Hospital Louisville
    • Louisiana
      • New Orleans, Louisiana, United States, 70121
        • Ochsner Clinic
      • New Orleans, Louisiana, United States, 70112
        • Tulane University Hospital and Clinic
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Beth Israel Deaconess Medical Center
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital
      • Boston, Massachusetts, United States, 02111
        • New England Medical Center
      • Burlington, Massachusetts, United States, 01805
        • Lahey Clinic
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • University Of Michigan
      • Detroit, Michigan, United States, 48202
        • Henry Ford Health System
    • Minnesota
      • Minneapolis, Minnesota, United States, 55455
        • University of Minnesota
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic Rochester
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Washington University School of Medicine
    • Nebraska
      • Omaha, Nebraska, United States, 68198
        • University of Nebraska
    • New Jersey
      • Newark, New Jersey, United States, 07101
        • University of Medicine and Dentistry of New Jersey
    • New York
      • New York, New York, United States, 10032
        • Columbia University Medical Center
      • New York, New York, United States, 10016
        • NYU School of Medicine
      • Rochester, New York, United States, 14642
        • University of Rochester Medical Center- Strong Memorial
      • Valhalla, New York, United States, 10595
        • New York Medical College
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27599
        • University of North Carolina, Chapel Hill
      • Durham, North Carolina, United States, 27710
        • Duke University Medical Center
    • Ohio
      • Cincinnati, Ohio, United States, 45267
        • University of Cincinnati Medical Center
      • Cleveland, Ohio, United States, 44195
        • Cleveland Clinic Foundation
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73112
        • Integris Baptist Medical Center
    • Oregon
      • Portland, Oregon, United States, 97239
        • Oregon Health and Sciences University
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • University of Pennsylvania Hospital
      • Pittsburgh, Pennsylvania, United States, 15240
        • VA Pittsburgh Healthcare System
    • South Carolina
      • Charleston, South Carolina, United States, 29425
        • Medical University of South Carolina
    • Tennessee
      • Memphis, Tennessee, United States, 38104
        • Methodist Transplant Institute
    • Texas
      • Dallas, Texas, United States, 75246
        • Baylor University Medical Center (Dallas)
      • Houston, Texas, United States, 77030
        • Methodist Hospital
      • Houston, Texas, United States, 77030
        • Baylor College of Medicine (Houston)
      • Houston, Texas, United States, 77030
        • UT Memorial Hermann Hospital and Texas Liver Center
      • San Antonio, Texas, United States, 78229
        • University of Texas Health Sciences Center at San Antonio
    • Virginia
      • Charlottesville, Virginia, United States, 22908
        • University of Virginia Health System
      • Richmond, Virginia, United States, 23298
        • Virginia Commonwealth University
    • Washington
      • Seattle, Washington, United States, 98195-7110
        • Univeristy of Washington Medical Center
    • Wisconsin
      • Milwaukee, Wisconsin, United States, 53226
        • Medical College of Wisconsin

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 1
Drug: maribavir
100mg twice a day for 14 weeks.
Active Comparator: 2
Drug: ganciclovir
1000mg three times per day for 14 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With Endpoint Committee (EC)-Confirmed Cytomegalovirus (CMV) Disease Within 6 Months Post-Transplantation
Time Frame: 6 months post-transplant
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With CMV Infection or EC-confirmed CMV Disease Within 6 Months Post-Transplantation
Time Frame: 6 months post-transplant
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
Time to Onset of CMV Infection or EC-confirmed CMV Disease Within 6 Months Post-Transplantation
Time Frame: 6 months post-transplant
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
Number of Participants With Investigator-determined CMV Disease
Time Frame: Through 6 months post-transplant (Day 1 to 100 days and 6 months post-transplant)
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)
Number of Participants With EC-confirmed CMV Disease Within 100 Days Post-Transplantation
Time Frame: 100 days post-transplant
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
Number of Participants With CMV Infection or EC-confirmed CMV Disease Within 100 Days Post-Transplantation
Time Frame: 100 days post-transplant
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
Number of Participants With Retransplantation
Time Frame: Through 6 months post-transplant (From Day 1 to 100 days and 6 months post-transplant)
Through 6 months post-transplant (From Day 1 to 100 days and 6 months post-transplant)
Number of Participants With Graft Failure Related Death
Time Frame: Through 6 months post-transplant (From Day 1 to 100 days and 6 months post-transplant)
Through 6 months post-transplant (From Day 1 to 100 days and 6 months post-transplant)
Number of Participants With Acute Graft Rejection
Time Frame: 26 weeks post-transplant
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
Number of Participants Who Died Within 6 Months Post-Transplantation
Time Frame: 6 months post-transplant
6 months post-transplant
Percent of Participants With Signs of Bone Marrow Suppression
Time Frame: 15 weeks
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
Plasma Concentration of Maribavir During Treatment
Time Frame: 12 hours post-dose after 2, 6, and 10 weeks of 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
Plasma Concentration of Maribavir Metabolite VP 44469 During Treatment
Time Frame: 12 hours post-dose after 2, 6, and 10 weeks of 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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Shire

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 23, 2007

Primary Completion (Actual)

September 14, 2009

Study Completion (Actual)

September 14, 2009

Study Registration Dates

First Submitted

July 5, 2007

First Submitted That Met QC Criteria

July 5, 2007

First Posted (Estimate)

July 9, 2007

Study Record Updates

Last Update Posted (Actual)

June 11, 2021

Last Update Submitted That Met QC Criteria

June 2, 2021

Last Verified

June 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 1263-301
  • 2007-004729-16 (EudraCT Number)
  • SHP620-301 (Other Identifier: Shire)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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