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CompletedNCT00411645Updated Jun 11, 2021Results posted

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

A Phase 3 interventional study of maribavir and placebo in Cytomegalovirus Infections, sponsored by Shire. Completed at 97 sites in 9 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2021-06-11.

Sponsored by Shire · Phase 3, Interventional, and Prevention

Phase
Phase 3
Study type
Interventional
Enrollment
681
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study 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.

Read the 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.

02

Conditions studied

  • Cytomegalovirus Infections

Keywords

  • prevention
  • prophylaxis
  • Cytomegalovirus
  • CMV
  • allogeneic stem cell transplant
  • SCT
03

In context

Cytomegalovirus Infections

359 studies on the registry are indexed under Cytomegalovirus Infections; 59 are open to participants now.

This study's enrollment of 681 is above the median of 60 across 233 interventional studies indexed under Cytomegalovirus Infections.

Browse Cytomegalovirus Infections studies →

Lead sponsor

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.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Allogeneic stem cell transplant recipient
  • Recipient or donor CMV seropositive
  • Have transplant engraftment
  • Able to swallow tablets

Exclusion criteria

Exclusion Criteria:

  • CMV organ disease
  • HIV infection
  • Use of other anti-CMV therapy post-transplant
05

Study design

Phase
Phase 3
Primary purpose
Prevention
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Triple (Participant, Care provider, Investigator)
Enrollment
681 participants (actual)

Study arms

  • Experimental
    A

    Drug: maribavir

  • Placebo comparator
    B

    Other: placebo

Interventions

  • Drugmaribavir

    100 mg twice daily for up to 12 weeks

  • Otherplacebo

    twice daily for up to 12 weeks

06

What researchers measure

Primary outcomes

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

    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.

    Time frame: 6 months post-transplant

Secondary outcomes

  1. Number of Participants With CMV Infection or EC-confirmed CMV Disease Within 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.

    Time frame: 6 months post-transplant

  2. Time to Onset of CMV Infection or EC-confirmed CMV Disease Within 6 Months Post- Transplantation

    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.

    Time frame: 6 months post-transplant

  3. Number of Participants With Investigator-determined CMV Disease

    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.

    Time frame: Through 12 months post-transplant (Day 1 to 100 days, 6 months, and 12 months post-transplant)

  4. Number of Participants With CMV Infection or EC-confirmed CMV Disease Within 100 Days Post-Transplantation

    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.

    Time frame: 100 days post-transplant

  5. Number of Participants With EC-confirmed CMV Disease Within 12 Months Post-Transplantation

    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.

    Time frame: 12 months post-transplant

  6. Percent of Participants With Acute Graft-Versus-Host Disease (GVHD)

    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.

    Time frame: Through 6 months post-transplant (Days 1 to 100 and 6 months post-transplant)

  7. Percent of Participants With Chronic Graft-Versus-Host Disease (GVHD)

    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.

    Time frame: Through 6 months post-transplant (Days 1 to 100 and 6 months post-transplant)

  8. Number of Participants Who Died Within 12 Months Post-Transplantation

    Time frame: Through 12 months post-transplant (Days 1 to 100, 6 months, and 12 months post-transplant)

  9. Plasma Concentration of Maribavir During 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.

    Time frame: 12 hours post-dose after 1 and 4 weeks of treatment

  10. Plasma Concentration of Maribavir Metabolite VP 44469 During 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 frame: 12 hours post-dose after 1 and 4 weeks of treatment

07

Results

Posted Jun 3, 2015

Participant flow

Participant flow — Overall Study
MilestonePlaceboMaribavir 100 mg BID
Started227454
Completed146290
Not completed81164
Withdrew: Consent withdrawn1322
Withdrew: Death56135
Withdrew: Investigator/sponsor decision107
Withdrew: Lost to follow-up20

Outcome measures

PrimaryNumber of Participants With Endpoint Committee (EC)-Confirmed Cytomegalovirus (CMV) Disease Within 6 Months Post-Transplantation

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.

Time frame:
6 months post-transplant
Reported as:
Number · participants
Number of Participants With Endpoint Committee (EC)-Confirmed Cytomegalovirus (CMV) Disease Within 6 Months Post-Transplantation
participantsPlaceboMaribavir 100 mg BID
Number of Participants With Endpoint Committee (EC)-Confirmed Cytomegalovirus (CMV) Disease Within 6 Months Post-Transplantation1120
Statistical analysis
  • Placebo vs Maribavir 100 mg BID · Cochran-Mantel-Haenszel · p = 0.789 (The p-value is from the Cochran-Mantel-Haenszel test, adjusting for recipient CMV serostatus (R+ or R-) and transplant type (myeloablative or non-myeloablative/reduced intensity).) · Odds ratio (or): 0.902 · 95% CI 0.424 to 1.920Mantel-Haenszel odds ratio for maribavir versus placebo
SecondaryNumber of Participants With CMV Infection or EC-confirmed CMV Disease Within 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.

Time frame:
6 months post-transplant
Reported as:
Number · participants
Number of Participants With CMV Infection or EC-confirmed CMV Disease Within 6 Months Post-transplant
participantsPlaceboMaribavir 100 mg BID
pp65 antigenemia assay88143
CMV DNA PCR assay77152
pp65 antigenemia or CMV DNA PCR assay101183
Initiation of anti-CMV therapy92172
Statistical analysis
  • Placebo vs Maribavir 100 mg BID · Cochran-Mantel-Haenszel · p = 0.056 (The p-value is from the Cochran-Mantel-Haenszel test, adjusting for recipient CMV serostatus (R+ or R-) and transplant type (myeloablative or non-myeloablative/reduced intensity).) · Odds ratio (or): 0.721 · 95% CI 0.515 to 1.008Mantel-Haenszel odds ratio for maribavir versus placebo
  • Placebo vs Maribavir 100 mg BID · Cochran-Mantel-Haenszel · p = 0.904 (The p-value is from the Cochran-Mantel-Haenszel test, adjusting for recipient CMV serostatus (R+ or R-) and transplant type (myeloablative or non-myeloablative/reduced intensity).) · Odds ratio (or): 0.979 · 95% CI 0.697 to 1.375Mantel-Haenszel odds ratio for maribavir versus placebo
  • Placebo vs Maribavir 100 mg BID · Cochran-Mantel-Haenszel · p = 0.289 (The p-value is from the Cochran-Mantel-Haenszel test, adjusting for recipient CMV serostatus (R+ or R-) and transplant type (myeloablative or non-myeloablative/reduced intensity).) · Odds ratio (or): 0.838 · 95% CI 0.606 to 1.161Mantel-Haenszel odds ratio for maribavir versus placebo
  • Placebo vs Maribavir 100 mg BID · Cochran-Mantel-Haenszel · p = 0.493 (The p-value is from the Cochran-Mantel-Haenszel test, adjusting for recipient CMV serostatus (R+ or R-) and transplant type (myeloablative or non-myeloablative/reduced intensity).) · Odds ratio (or): 0.891 · 95% CI 0.640 to 1.239Mantel-Haenszel odds ratio for maribavir versus placebo
SecondaryTime to Onset of CMV Infection or EC-confirmed CMV Disease Within 6 Months Post- Transplantation

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.

Time frame:
6 months post-transplant
Reported as:
Median · days
Time to Onset of CMV Infection or EC-confirmed CMV Disease Within 6 Months Post- Transplantation
daysPlaceboMaribavir 100 mg BID
Time to Onset of CMV Infection or EC-confirmed CMV Disease Within 6 Months Post- Transplantation21 (5 to 22)22 (6 to 29)
Statistical analysis
  • Placebo vs Maribavir 100 mg BID · Log Rank · p = 0.129
  • Placebo vs Maribavir 100 mg BID · Wald Chi-squared · p = 0.130 (The p-value from Wald Chi-Square test for treatment effect.) · Adjusted hazard ratio: 0.83 · 95% CI 0.65 to 1.06Maribavir versus placebo; based on Cox's proportional hazards regression model: time = recipient CMV serostatus (R+ or R-) + transplant type (myeloablative or non-myeloablative/reduced intensity) + treatment.
SecondaryNumber of Participants With Investigator-determined CMV Disease

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.

Time frame:
Through 12 months post-transplant (Day 1 to 100 days, 6 months, and 12 months post-transplant)
Reported as:
Number · participants
Number of Participants With Investigator-determined CMV Disease
participantsPlaceboMaribavir 100 mg BID
100 days post-tranplant616
6 months post-transplant1126
12 months post-transplant1328
Statistical analysis
  • Placebo vs Maribavir 100 mg BID · Cochran-Mantel-Haenszel · p = 0.542 (The p-value is from the Cochran-Mantel-Haenszel test, adjusting for recipient CMV serostatus (R+ or R-) and transplant type (myeloablative or non-myeloablative/reduced intensity).)
  • Placebo vs Maribavir 100 mg BID · Cochran-Mantel-Haenszel · p = 0.637 (The p-value is from the Cochran-Mantel-Haenszel test, adjusting for recipient CMV serostatus (R+ or R-) and transplant type (myeloablative or non-myeloablative/reduced intensity).)
  • Placebo vs Maribavir 100 mg BID · Cochran-Mantel-Haenszel · p = 0.825 (The p-value is from the Cochran-Mantel-Haenszel test, adjusting for recipient CMV serostatus (R+ or R-) and transplant type (myeloablative or non-myeloablative/reduced intensity).)
SecondaryNumber of Participants With CMV Infection or EC-confirmed CMV Disease Within 100 Days Post-Transplantation

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.

Time frame:
100 days post-transplant
Reported as:
Number · participants
Number of Participants With CMV Infection or EC-confirmed CMV Disease Within 100 Days Post-Transplantation
participantsPlaceboMaribavir 100 mg BID
pp65 antigenemia assay79120
CMV DNA PCR assay69126
pp65 antigenemia assay or CMV DNA PCR assay92157
Initiation of anti-CMV therapy85139
EC-confirmed disease611
Statistical analysis
  • Placebo vs Maribavir 100 mg BID · Cochran-Mantel-Haenszel · p = 0.022 (The p-value is from the Cochran-Mantel-Haenszel test, adjusting for recipient CMV serostatus (R+ or R-) and transplant type (myeloablative or non-myeloablative/reduced intensity).) · Odds ratio (or): 0.669 · 95% CI 0.474 to 0.946Mantel-Haenszel odds ratio for maribavir versus placebo
  • Placebo vs Maribavir 100 mg BID · Cochran-Mantel-Haenszel · p = 0.468 (The p-value is from the Cochran-Mantel-Haenszel test, adjusting for recipient CMV serostatus (R+ or R-) and transplant type (myeloablative or non-myeloablative/reduced intensity).) · Odds ratio (or): 0.878 · 95% CI 0.617 to 1.247Mantel-Haenszel odds ratio for maribavir versus placebo
  • Placebo vs Maribavir 100 mg BID · Cochran-Mantel-Haenszel · p = 0.125 (The p-value is from the Cochran-Mantel-Haenszel test, adjusting for recipient CMV serostatus (R+ or R-) and transplant type (myeloablative or non-myeloablative/reduced intensity).) · Odds ratio (or): 0.772 · 95% CI 0.555 to 1.075Mantel-Haenszel odds ratio for maribavir versus placebo
  • Placebo vs Maribavir 100 mg BID · Cochran-Mantel-Haenszel · p = 0.069 (The p-value is from the Cochran-Mantel-Haenszel test, adjusting for recipient CMV serostatus (R+ or R-) and transplant type (myeloablative or non-myeloablative/reduced intensity).) · Odds ratio (or): 0.731 · 95% CI 0.521 to 1.026Mantel-Haenszel odds ratio for maribavir versus placebo
  • Placebo vs Maribavir 100 mg BID · Cochran-Mantel-Haenszel · p = 0.860 (The p-value is from the Cochran-Mantel-Haenszel test, adjusting for recipient CMV serostatus (R+ or R-) and transplant type (myeloablative or non-myeloablative/reduced intensity).) · Odds ratio (or): 0.913 · 95% CI 0.332 to 2.508Mantel-Haenszel odds ratio for maribavir versus placebo
SecondaryNumber of Participants With EC-confirmed CMV Disease Within 12 Months Post-Transplantation

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.

Time frame:
12 months post-transplant
Reported as:
Number · participants
Number of Participants With EC-confirmed CMV Disease Within 12 Months Post-Transplantation
participantsPlaceboMaribavir 100 mg BID
Number of Participants With EC-confirmed CMV Disease Within 12 Months Post-Transplantation1322
Statistical analysis
  • Placebo vs Maribavir 100 mg BID · Cochran-Mantel-Haenszel · p = 0.617 (The p-value is from the Cochran-Mantel-Haenszel test, adjusting for recipient CMV serostatus (R+ or R-) and transplant type (myeloablative or non-myeloablative/reduced intensity).) · Odds ratio (or): 0.835 · 95% CI 0.411 to 1.693Mantel-Haenszel odds ratio for maribavir versus placebo
SecondaryPercent of Participants With Acute Graft-Versus-Host Disease (GVHD)

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.

Time frame:
Through 6 months post-transplant (Days 1 to 100 and 6 months post-transplant)
Reported as:
Number · percentage of participants
Percent of Participants With Acute Graft-Versus-Host Disease (GVHD)
percentage of participantsPlaceboMaribavir 100 mg BID
100 days post-transplant3940
6 months post-transplant4344
Statistical analysis
  • Placebo vs Maribavir 100 mg BID · Cochran-Mantel-Haenszel · p = 0.7808 (The p-value is from the Cochran-Mantel-Haenszel test, adjusting for recipient CMV serostatus (R+ or R -) and transplant type (myeloablative or non-myeloablative/reduced intensity).) · Odds ratio (or): 1.048 · 95% CI 0.754 to 1.457Mantel-Haenszel odds ratio for maribavir versus placebo
  • Placebo vs Maribavir 100 mg BID · Cochran-Mantel-Haenszel · p = 0.6946 (The p-value is from the Cochran-Mantel-Haenszel test, adjusting for recipient CMV serostatus (R+ or R -) and transplant type (myeloablative or non-myeloablative/reduced intensity).) · Odds ratio (or): 1.068 · 95% CI 0.771 to 1.479Mantel-Haenszel odds ratio for maribavir versus placebo
SecondaryPercent of Participants With Chronic Graft-Versus-Host Disease (GVHD)

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.

Time frame:
Through 6 months post-transplant (Days 1 to 100 and 6 months post-transplant)
Reported as:
Number · percentage of participants
Percent of Participants With Chronic Graft-Versus-Host Disease (GVHD)
percentage of participantsPlaceboMaribavir 100 mg BID
100 days post-transplant56
6 months post-transplant2519
Statistical analysis
  • Placebo vs Maribavir 100 mg BID · Cochran-Mantel-Haenszel · p = 0.6304 (The p-value is from the Cochran-Mantel-Haenszel test, adjusting for recipient CMV serostatus (R+ or R -) and transplant type (myeloablative or non-myeloablative/reduced intensity).) · Odds ratio (or): 1.186 · 95% CI 0.592 to 2.375Mantel-Haenszel odds ratio for maribavir versus placebo
  • Placebo vs Maribavir 100 mg BID · Cochran-Mantel-Haenszel · p = 0.1019 (The p-value is from the Cochran-Mantel-Haenszel test, adjusting for recipient CMV serostatus (R+ or R -) and transplant type (myeloablative or non-myeloablative/reduced intensity).) · Odds ratio (or): 0.726 · 95% CI 0.495 to 1.066Mantel-Haenszel odds ratio for maribavir versus placebo
SecondaryNumber of Participants Who Died Within 12 Months Post-Transplantation
Time frame:
Through 12 months post-transplant (Days 1 to 100, 6 months, and 12 months post-transplant)
Reported as:
Number · participants
Number of Participants Who Died Within 12 Months Post-Transplantation
participantsPlaceboMaribavir 100 mg BID
100 days post-transplant1930
6 months post-transplant3788
12 months post-transplant59139
SecondaryPlasma Concentration of Maribavir During 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.

Time frame:
12 hours post-dose after 1 and 4 weeks of treatment
Reported as:
Mean · μg/mL
Plasma Concentration of Maribavir During Treatment
μg/mLMaribavir 100 mg BID
1 week post-dose, n=632.11 ± 2.10
4 weeks post-dose, n=482.19 ± 1.99
SecondaryPlasma Concentration of Maribavir Metabolite VP 44469 During 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 frame:
12 hours post-dose after 1 and 4 weeks of treatment
Reported as:
Mean · μg/mL
Plasma Concentration of Maribavir Metabolite VP 44469 During Treatment
μg/mLMaribavir 100 mg BID
1 week post-dose, n=630.56 ± 0.36
4 weeks post-dose, n=480.65 ± 0.47

Adverse events

Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Placebo—98/223 (43.9%)192/223 (86.1%)
Maribavir 100 mg BID—197/451 (43.7%)408/451 (90.5%)
Most frequent serious events
Showing 10 of 169
Most frequent serious events
EventPlaceboMaribavir 100 mg BID
Acute Graft Versus Host DiseaseImmune system disorders25/22356/451
PyrexiaGeneral disorders14/22328/451
Relapse of underlying diseaseBlood and lymphatic system disorders13/22321/451
Leukaemia RecurrentBlood and lymphatic system disorders6/22315/451
Renal FailureRenal and urinary disorders4/22314/451
Febrile NeutropeniaBlood and lymphatic system disorders6/2234/451
Cytomegalovirus InfectionInfections and infestations4/22310/451
BacteraemiaInfections and infestations3/2239/451
Staphylococcal BacteraemiaInfections and infestations3/2239/451
Non-Hodgkin's Lymphoma RecurrentBlood and lymphatic system disorders4/2235/451
Most frequent other events
Showing 10 of 35
Most frequent other events
EventPlaceboMaribavir 100 mg BID
Acute Graft Versus Host DiseaseImmune system disorders50/223117/451
DiarrhoeaGastrointestinal disorders41/22386/451
FatigueGeneral disorders22/22373/451
NauseaGastrointestinal disorders33/22368/451
DysgeusiaGastrointestinal disorders13/22366/451
RashSkin and subcutaneous tissue disorders30/22359/451
AnaemiaBlood and lymphatic system disorders17/22360/451
Weight DecreasedInvestigations29/22341/451
Oedema PeripheralGeneral disorders28/22358/451
PyrexiaGeneral disorders28/22346/451

Baseline characteristics

Age, Continuous
Age, Continuous(years)PlaceboMaribavir 100 mg BIDTotal
Mean49 ± 13.149 ± 12.549 ± 12.7
Age, Customized
Age, Customized(Participants)PlaceboMaribavir 100 mg BIDTotal
18 to 44 years74136210
45 to 64 years134286420
65 to 75 years183250
> 75 years101
Sex: Female, Male
Sex: Female, Male(Participants)PlaceboMaribavir 100 mg BIDTotal
Female98189287
Male129265394
08

Study locations

97 sites
  • University of Arkansas Myeloma Institute
    Little Rock, Arkansas 72205, United States
  • City of Hope Medical Center
    Duarte, California 91010, United States
  • Scripps Green Hospital
    La Jolla, California 92037, United States
  • UCSD Moores Center
    La Jolla, California 92093-0960, United States
  • UCLA Medical Center
    Los Angeles, California 90095-1678, United States
  • University of California, San Francisco
    San Francisco, California 94143, United States
  • Stanford University Medical Center
    Stanford, California 94305, United States
  • Rocky Mountain Cancer Center
    Denver, Colorado 80218, United States
  • Shands Hospital
    Gainesville, Florida 32610, United States
  • H. Lee Moffitt Cancer Center
    Tampa, Florida 33612, United States
  • Emory University
    Atlanta, Georgia 30322, United States
  • Northwestern University Medical Center
    Chicago, Illinois 60611, United States
  • University of Chicago
    Chicago, Illinois 60637, United States
  • Loyola University
    Maywood, Illinois 60153, United States
  • St Francis Hospital
    Beech Grove, Indiana 46107, United States
  • University of Iowa Hospitals and Clinics
    Iowa City, Iowa 52242, United States
  • University of Kentucky Chandler Medical Center
    Lexington, Kentucky 40536, United States
  • University Medical Center University of Louisville Hospital
    Louisville, Kentucky 40202, United States
  • Greenbaum Cancer Center
    Baltimore, Maryland 21201-1595, United States
  • Massachusettes General
    Boston, Massachusetts 02114, United States
  • Brigham and Women's Hospital
    Boston, Massachusetts 02115, United States
  • Beth Israel Deaconess Medical Center
    Boston, Massachusetts 02215, United States
  • University of Michigan
    Ann Arbor, Michigan 48109-0914, United States
  • Wayne State Medical Center
    Detroit, Michigan 48201, United States
  • Henry Ford Health System
    Detroit, Michigan 48202, United States
  • University of Minnesota
    Minneapolis, Minnesota 55455, United States
  • Mayo Clinic College of Medicine
    Rochester, Minnesota 55905, United States
  • Washington University School of Medicine
    Saint Louis, Missouri 63110, United States
  • Hackensack University Medical Center
    Hackensack, New Jersey 07601, United States
  • Roswell Park Cancer Institute
    Buffalo, New York 14263, United States
  • Memorial Sloan-Kettering Cancer Center
    New York, New York 10021, United States
  • New York Presbyterian Hospital,Weill Cornell Medical Center
    New York, New York 10021, United States
  • Mount Sinai Hospital
    New York, New York 10029, United States
  • University of Rochester Medical Center
    Rochester, New York 14642, United States
  • University of North Carolina Hospital
    Chapel Hill, North Carolina 27599, United States
  • Duke Medical Center
    Durham, North Carolina 27710, United States
  • Wake Forest Medical Center
    Winston-Salem, North Carolina 27157, United States
  • The Jewish Hospital
    Cincinnati, Ohio 45236, United States
  • Ireland Cancer Center Case Western Reserve University
    Cleveland, Ohio 44106, United States
  • University of Oklahoma
    Oklahoma City, Oklahoma 73104, United States
  • Oregon Health and Sciences University
    Portland, Oregon 97239-3098, United States
  • Penn State Milton S. Hershey Medical Center
    Hershey, Pennsylvania 17033, United States
  • Thomas Jefferson
    Philadelphia, Pennsylvania 19107, United States
  • Jeanes Hospital - Temple
    Philadelphia, Pennsylvania 19111, United States
  • Western Pennsylvania Cancer Institute
    Pittsburgh, Pennsylvania 15224, United States
  • University of Pittsburgh Cancer Institute
    Pittsburgh, Pennsylvania 15232, United States
  • Vanderbilt Medical Center
    Nashville, Tennessee 37232, United States
  • Baylor University Medical Center
    Dallas, Texas 75246, United States
  • MD Anderson Cancer Center
    Houston, Texas 77030-4009, United States
  • Methodist Hospital
    Houston, Texas 77030, United States
  • Texas Transplant Institute
    San Antonio, Texas 78229, United States
  • Latter Day Saints Hospital
    Salt Lake City, Utah 84103, United States
  • Medical College of Virginia
    Richmond, Virginia 23298, United States
  • VA Puget Sound Health Center
    Seattle, Washington 98108, United States
  • Fred Hutchinson Cancer Research Center
    Seattle, Washington 98109, United States
  • West Virginia University Hospital
    Morgantown, West Virginia 26506-9162, United States
  • ZNA Stuivenberg
    Antwerp, 2060, Belgium
  • AZ Sint Jan, Department of Hematology
    Brugge, 8000, Belgium
  • Cliniques Universitaires St,Luc Dept Hematology
    Brussels, 1200, Belgium
  • UZ Gasthuisberg
    Leuven, 3000, Belgium
  • CHU Sart -Tilman Department of Medicine, Hematology
    Liege, 4000, Belgium
  • QEII Health Sciences Center
    Halifax, Nova Scotia B3H2Y9, Canada
  • McMaster University Medical Center
    Hamilton, Ontario L8N 3Z5, Canada
  • London Health Sciences Centre
    London, Ontario N6A 4G5, Canada
  • Ottawa General Campus
    Ottawa,, Ontario K1H 8L6, Canada
  • Hopital l'Enfant Jesus
    Quebec, G1J 1Z4, Canada
  • Hopital Henri Mondor
    Créteil, 94010, France
  • Edouard Herriot Hopital
    Lyon, Cedex 03, 69437, France
  • Institut Paoli Calmettes
    Marseille Cedex 9, 13273, France
  • Hopital Hotel Dieu
    Nantes, Cedex 1, 44093, France
  • Hopital St. Louis
    Paris Cedex 10, 75475, France
  • Hopital Haut-Leveque
    Pessac, 33600, France
  • Univ. Clinic Dresden
    Dresden, 01307, Germany
  • University Clinic of Dresden
    Dresden, 01307, Germany
  • University of Essen
    Essen, 45122, Germany
  • University of Freiburg
    Freiburg, 79106, Germany
  • University of Hamburg-Eppendorf
    Hamburg, 20246, Germany
  • Hannover, Medizinische Hochschule
    Hannover, 30625, Germany
  • University of Heidelberg
    Heidelberg, 69120, Germany
  • Universitaetsklinikum Koeln, Clinic I for internal Medicine
    Koeln, 50937, Germany
  • Johannes-Gutenberg University
    Mainz, 55131, Germany
  • University Clinic of Ulm
    Ulm, 89081, Germany
  • Careggi University Hospital
    Firenze, 50134, Italy
  • University of San Martino Hospital
    Genova, 16132, Italy
  • San Raffaele del Monte Tabor
    Milano, 20132, Italy
  • Pescara Hospital
    Pescara, 65123, Italy
  • Bianchi-Melacrino-Morelli Hospital
    Reggio Calabria, 89100, Italy
  • Barcelona Hospital
    Barcelona, 08036, Spain
  • Duran i Reynals Hospital
    Barcelona, 08907, Spain
  • University of Salamanca
    Salamanca, E-37007, Spain
  • Karolinska University Hospital
    Huddinge, Stockholm 14186, Sweden
  • Sahlgrenska University Hospital
    Goteborg, S-413 45, Sweden
  • Karolinska University Hospital,Huddinge
    Stockholm, 141 86, Sweden
  • Akademiska Sjukhuset, Dept Hematology
    Uppsala, 751 85, Sweden
  • University College Hospital
    London, NW1 2BU, United Kingdom
  • Royal Free Hospital
    London, NW3 2QG, United Kingdom
  • Hammersmith Hospital
    London, W12 OHS, United Kingdom
09

References and documents

Publications

  • Marty FM, Ljungman P, Papanicolaou GA, Winston DJ, Chemaly RF, Strasfeld L, Young JA, Rodriguez T, Maertens J, Schmitt M, Einsele H, Ferrant A, Lipton JH, Villano SA, Chen H, Boeckh M; Maribavir 1263-300 Clinical Study Group. Maribavir prophylaxis for prevention of cytomegalovirus disease in recipients of allogeneic stem-cell transplants: a phase 3, double-blind, placebo-controlled, randomised trial. Lancet Infect Dis. 2011 Apr;11(4):284-92. doi: 10.1016/S1473-3099(11)70024-X. Epub 2011 Mar 21. Erratum In: Lancet Infect Dis. 2011 May;11(5):343. PubMed 21414843 ↗
10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jun 11, 2021, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT00411645
Lead sponsor
Shire
Responsible party
Sponsor
First posted
Dec 14, 2006
Start date
Dec 13, 2006
Primary completion
Nov 10, 2008
Completion
May 23, 2009
Results posted
Jun 3, 2015
Last update
Jun 11, 2021

Study contacts

Study Director
study director · Takeda

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

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