Prophylactic Use of Maribavir for the Prevention of Cytomegalovirus (CMV) Disease in Stem Cell Transplant Recipients
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| ClinicalTrials.gov Identifier: NCT00411645 |
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Recruitment Status :
Completed
First Posted : December 14, 2006
Results First Posted : June 3, 2015
Last Update Posted : June 11, 2021
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Sponsor:
Shire
Information provided by (Responsible Party):
Takeda ( Shire )
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Brief 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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Cytomegalovirus Infections | Drug: maribavir Other: placebo | Phase 3 |
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.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 681 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Triple (Participant, Care Provider, Investigator) |
| Primary Purpose: | Prevention |
| Official Title: | A Randomized, Double-blind, Placebo-controlled Study to Assess the Efficacy and Safety of Prophylactic Use of Maribavir for the Prevention of Cytomegalovirus Disease in Recipients of Allogeneic Stem Cell Transplants. |
| Actual Study Start Date : | December 13, 2006 |
| Actual Primary Completion Date : | November 10, 2008 |
| Actual Study Completion Date : | May 23, 2009 |
Resource links provided by the National Library of Medicine
MedlinePlus related topics:
Cytomegalovirus Infections
Drug Information available for:
Maribavir
| Arm | Intervention/treatment |
|---|---|
| Experimental: A |
Drug: maribavir
100 mg twice daily for up to 12 weeks |
| Placebo Comparator: B |
Other: placebo
twice daily for up to 12 weeks |
Primary Outcome Measures :
- 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 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.
Secondary Outcome Measures :
- Number of Participants With CMV Infection or EC-confirmed CMV Disease Within 6 Months Post-transplant [ Time Frame: 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 to Onset of CMV Infection or EC-confirmed CMV Disease Within 6 Months Post- Transplantation [ Time Frame: 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 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.
- Number of Participants With Investigator-determined CMV Disease [ Time Frame: Through 12 months post-transplant (Day 1 to 100 days, 6 months, and 12 months post-transplant) ]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.
- Number of Participants With CMV Infection or EC-confirmed CMV Disease Within 100 Days Post-Transplantation [ Time Frame: 100 days 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.
- Number of Participants With EC-confirmed CMV Disease Within 12 Months Post-Transplantation [ Time Frame: 12 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.
- Percent of Participants With Acute Graft-Versus-Host Disease (GVHD) [ Time Frame: Through 6 months post-transplant (Days 1 to 100 and 6 months post-transplant) ]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.
- Percent of Participants With Chronic Graft-Versus-Host Disease (GVHD) [ Time Frame: Through 6 months post-transplant (Days 1 to 100 and 6 months post-transplant) ]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.
- 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) ]
- Plasma Concentration of Maribavir During Treatment [ Time Frame: 12 hours post-dose after 1 and 4 weeks of 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.
- Plasma Concentration of Maribavir Metabolite VP 44469 During Treatment [ Time Frame: 12 hours post-dose after 1 and 4 weeks of 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.
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Allogeneic stem cell transplant recipient
- Recipient or donor CMV seropositive
- Have transplant engraftment
- Able to swallow tablets
Exclusion Criteria:
- CMV organ disease
- HIV infection
- Use of other anti-CMV therapy post-transplant
Information from the National Library of Medicine
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): NCT00411645
Locations
Show 97 study locations
Sponsors and Collaborators
Shire
Investigators
| Study Director: | Study Director | Takeda |
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Shire |
| ClinicalTrials.gov Identifier: | NCT00411645 |
| Obsolete Identifiers: | NCT00430339 |
| Other Study ID Numbers: |
1263-300 2006-005692-18 ( EudraCT Number ) SHP620-300 ( Other Identifier: Shire ) |
| First Posted: | December 14, 2006 Key Record Dates |
| Results First Posted: | June 3, 2015 |
| Last Update Posted: | June 11, 2021 |
| Last Verified: | June 2021 |
Keywords provided by Takeda ( Shire ):
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prevention prophylaxis Cytomegalovirus |
CMV allogeneic stem cell transplant SCT |
Additional relevant MeSH terms:
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Cytomegalovirus Infections Herpesviridae Infections DNA Virus Infections Virus Diseases |
Infections Maribavir Antiviral Agents Anti-Infective Agents |