A Phase 3 interventional study of maribavir and ganciclovir in Cytomegalovirus Infections, sponsored by Shire. Completed at 55 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2021-06-11.
Sponsored by Shire · Phase 3, Interventional, and Prevention
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.
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.
359 studies on the registry are indexed under Cytomegalovirus Infections; 59 are open to participants now.
This study's enrollment of 307 is above the median of 60 across 233 interventional studies indexed under Cytomegalovirus Infections.
Browse Cytomegalovirus Infections studies →Shire is the lead sponsor of 346 studies on the registry; 2 are open to participants now.
Of its 47 completed or terminated interventional studies of FDA-regulated products, 47 (100%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
Drug: maribavir
Drug: ganciclovir
100mg twice a day for 14 weeks.
1000mg three times per day for 14 weeks.
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.
Time frame: 6 months post-transplant
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.
Time frame: 6 months post-transplant
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.
Time frame: 6 months post-transplant
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.
Time frame: 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
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.
Time frame: 100 days post-transplant
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.
Time frame: 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)
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
Rejection was assessed by examining a liver biopsy sample. Diagnosis of graft rejection included a global assessment grade and a rejection activity index score.
Time frame: 26 weeks post-transplant
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
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.
Time frame: 15 weeks
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.
Time frame: 12 hours post-dose after 2, 6, and 10 weeks of treatment
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.
Time frame: 12 hours post-dose after 2, 6, and 10 weeks of treatment
| Milestone | Maribavir 100 mg BID | Ganciclovir 1000 mg TID |
|---|---|---|
| Started | 147 | 160 |
| Completed | 62 | 101 |
| Not completed | 85 | 59 |
| Withdrew: Adverse event (not related) | 9 | 9 |
| Withdrew: Adverse event (related) | 5 | 4 |
| Withdrew: Cmv infection or disease treatment | 30 | 4 |
| Withdrew: Consent withdrawn | 10 | 3 |
| Withdrew: Investigator/sponsor discretion | 31 | 34 |
| Withdrew: Lost to follow-up | 0 | 1 |
| Withdrew: Not applicable (randomized not treated) | 0 | 4 |
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 event | Maribavir 100 mg BID | Ganciclovir 1000 mg TID |
|---|---|---|
| Number of Participants With Endpoint Committee (EC)-Confirmed Cytomegalovirus (CMV) Disease Within 6 Months Post-Transplantation | 14 | 10 |
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.
| participants | Maribavir 100 mg BID | Ganciclovir 1000 mg TID |
|---|---|---|
| pp65 antigenemia assay | 63 | 49 |
| CMV DNA PCR assay | 72 | 52 |
| pp65 antigenemia or CMV DNA PCR assay | 81 | 64 |
| Initiation of anti-CMV therapy | 46 | 39 |
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.
| days | Maribavir 100 mg BID | Ganciclovir 1000 mg TID |
|---|---|---|
| Time to Onset of CMV Infection or EC-confirmed CMV Disease Within 6 Months Post-Transplantation | 45 (41 to 68) | 127 (125 to 161) |
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.
| participants | Maribavir 100 mg BID | Ganciclovir 1000 mg TID |
|---|---|---|
| 100 days post-transplant | 17 | 3 |
| 6 months post-transplant | 22 | 18 |
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.
| participants | Maribavir 100 mg BID | Ganciclovir 1000 mg TID |
|---|---|---|
| Number of Participants With EC-confirmed CMV Disease Within 100 Days Post-Transplantation | 10 | 0 |
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.
| participants | Maribavir 100 mg BID | Ganciclovir 1000 mg TID |
|---|---|---|
| pp65 antigenemia assay | 49 | 19 |
| CMV DNA PCR assay | 59 | 18 |
| pp65 antigenemia or CMV DNA PCR assay | 68 | 24 |
| Initiation of anti-CMV therapy | 37 | 5 |
| participants | Maribavir 100 mg BID | Ganciclovir 1000 mg TID |
|---|---|---|
| At 100 days post-transplant | 1 | 2 |
| At 6 months post-transplant | 2 | 2 |
| participants | Maribavir 100 mg BID | Ganciclovir 1000 mg TID |
|---|---|---|
| 100 days post-transplant | 0 | 2 |
| 6 months post-transplant | 1 | 2 |
Rejection was assessed by examining a liver biopsy sample. Diagnosis of graft rejection included a global assessment grade and a rejection activity index score.
| participants | Maribavir 100 mg BID | Ganciclovir 1000 mg TID |
|---|---|---|
| 100 days post-transplant | 16 | 19 |
| 6 months post-transplant | 20 | 23 |
| participants | Maribavir 100 mg BID | Ganciclovir 1000 mg TID |
|---|---|---|
| Number of Participants Who Died Within 6 Months Post-Transplantation | 9 | 6 |
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.
| percent of participants | Maribavir 100 mg BID | Ganciclovir 1000 mg TID |
|---|---|---|
| Hematology AEs | 14 | 21 |
| ANC <1000/mm3 | 9 | 16 |
| WBC count toxicity grade shifts | 16 | 21 |
| Use of hematopoietic growth factors | 15 | 20 |
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.
| μg/mL | Maribavir 100 mg BID |
|---|---|
| 2 weeks, n=10 | 1.65 ± 2.01 |
| 6 weeks, n=7 | 1.36 ± 1.25 |
| 10 weeks, n=8 | 1.55 ± 1.17 |
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.
| μg/mL | Maribavir 100 mg BID |
|---|---|
| 2 weeks, n=10 | 0.609 ± 0.648 |
| 6 weeks, n=7 | 0.506 ± 0.224 |
| 10 weeks, n=8 | 0.666 ± 0.656 |
Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Maribavir 100 mg BID | — | 71/147 (48.3%) | 127/147 (86.4%) |
| Ganciclovir 1000 mg TID | — | 76/156 (48.7%) | 140/156 (89.7%) |
| Event | Maribavir 100 mg BID | Ganciclovir 1000 mg TID |
|---|---|---|
| Cytomegalovirus InfectionInfections and infestations | 12/147 | 2/156 |
| Liver Transplant RejectionImmune system disorders | 4/147 | 12/156 |
| Hepatic Enzyme IncreasedInvestigations | 8/147 | 4/156 |
| PyrexiaGeneral disorders | 4/147 | 7/156 |
| Bile Duct StenosisHepatobiliary disorders | 4/147 | 2/156 |
| Post Procedural Bile LeakHepatobiliary disorders | 4/147 | 2/156 |
| Renal FailureRenal and urinary disorders | 4/147 | 3/156 |
| AnaemiaBlood and lymphatic system disorders | 1/147 | 4/156 |
| DiarrhoeaGastrointestinal disorders | 2/147 | 4/156 |
| AscitesHepatobiliary disorders | 3/147 | 4/156 |
| Event | Maribavir 100 mg BID | Ganciclovir 1000 mg TID |
|---|---|---|
| DiarrhoeaGastrointestinal disorders | 41/147 | 36/156 |
| HeadacheNervous system disorders | 20/147 | 29/156 |
| NauseaGastrointestinal disorders | 14/147 | 28/156 |
| TremorNervous system disorders | 25/147 | 20/156 |
| DysgeusiaGastrointestinal disorders | 22/147 | 20/156 |
| Urinary Tract InfectionRenal and urinary disorders | 22/147 | 11/156 |
| HyperkalaemiaMetabolism and nutrition disorders | 19/147 | 21/156 |
| HypertensionVascular disorders | 18/147 | 21/156 |
| Oedema PeripheralGeneral disorders | 19/147 | 15/156 |
| LeukopeniaBlood and lymphatic system disorders | 12/147 | 19/156 |
The Intent-to-Treat Safety (ITT-S) population, defined as all randomized subjects who received at least one dose of study drug, regardless of whether they had any post-baseline evaluations.
| Age, Continuous(years) | Maribavir 100 mg BID | Ganciclovir 1000 mg TID | Total |
|---|---|---|---|
| Mean | 55 ± 9.0 | 53 ± 8.9 | 54 ± 9.0 |
| Sex: Female, Male(Participants) | Maribavir 100 mg BID | Ganciclovir 1000 mg TID | Total |
|---|---|---|---|
| Female | 27 | 37 | 64 |
| Male | 120 | 119 | 239 |
| Distribution of age(Participants) | Maribavir 100 mg BID | Ganciclovir 1000 mg TID | Total |
|---|---|---|---|
| 18 to 44 years | 19 | 22 | 41 |
| 45 to 64 years | 109 | 123 | 232 |
| 65 to 75 years | 19 | 11 | 30 |
This study is completed, as verified in Jun 2021. You cannot join it, but the record below documents what was studied.
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