Maribavir Versus Oral Ganciclovir For The Prevention of Cytomegalovirus (CMV) Disease in Liver Transplant Recipients
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ClinicalTrials.gov Identifier: NCT00497796 |
Recruitment Status
:
Completed
First Posted
: July 9, 2007
Results First Posted
: June 4, 2015
Last Update Posted
: June 4, 2015
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Condition or disease | Intervention/treatment | Phase |
---|---|---|
Cytomegalovirus Infections | Drug: maribavir Drug: ganciclovir | Phase 3 |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 307 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | Triple (Participant, Care Provider, Investigator) |
Primary Purpose: | Prevention |
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 |
Study Start Date : | July 2007 |
Actual Primary Completion Date : | May 2009 |
Actual Study Completion Date : | September 2009 |
Arm | Intervention/treatment |
---|---|
Experimental: 1 |
Drug: maribavir
100mg twice a day for 14 weeks.
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Active Comparator: 2 |
Drug: ganciclovir
1000mg three times per day for 14 weeks.
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- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- Number of Participants With Retransplantation [ Time Frame: 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) ]
- 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.
- Number of Participants Who Died Within 6 Months Post-Transplantation [ Time Frame: 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.
- 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.
- 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.

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Ages Eligible for Study: | 18 Years and older (Adult, Senior) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
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

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00497796

Study Director: | Stephen A Villano, MD | ViroPharma |
Responsible Party: | Shire |
ClinicalTrials.gov Identifier: | NCT00497796 History of Changes |
Other Study ID Numbers: |
1263-301 2007-004729-16 ( EudraCT Number ) SHP620-301 ( Other Identifier: Shire ) |
First Posted: | July 9, 2007 Key Record Dates |
Results First Posted: | June 4, 2015 |
Last Update Posted: | June 4, 2015 |
Last Verified: | March 2014 |
Keywords provided by Shire:
cytomegalovirus CMV prophylaxis liver liver transplant |
Additional relevant MeSH terms:
Cytomegalovirus Infections Herpesviridae Infections DNA Virus Infections Virus Diseases Ganciclovir Ganciclovir triphosphate |
Antiviral Agents Anti-Infective Agents Nucleic Acid Synthesis Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action |