Maribavir for Treatment of Resistant or Refractory CMV Infections in Transplant Recipients
- Registration Number
- NCT01611974
- Lead Sponsor
- Shire
- Brief Summary
This study will assess safety, antiviral activity, and pharmacokinetics of different doses of maribavir administered orally for up to 24 weeks for treatment of CMV infections that are resistant or refractory to treatment with ganciclovir/valganciclovir or foscarnet in recipients of stem cell or solid organ transplants.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 120
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Maribavir 400 mg twice daily Maribavir - Maribavir 800 mg twice daily Maribavir - Maribavir 1200 mg twice daily Maribavir -
- Primary Outcome Measures
Name Time Method Number of Participants With a Treatment Emergent Adverse Event (TEAE). 25 weeks Treatment-emergent adverse events are those events that occurred on or after study drug administration through 7 days after the last dose of study drug, or are events that occurred prior to study drug administration and recurred with increased severity after taking study drug through 7 days after the last dose of study drug.
Number of Participants With Confirmed Undetectable Plasma Cytomegalovirus (CMV) Within 6 Weeks 6 weeks Blood samples were collected at the study sites, processed to plasma aliquots, and sent to the central laboratory for quantitative CMV DNA polymerase chain reaction (PCR) testing. Plasma samples were assayed for CMV concentration using a qualified PCR method. This method was linear over 200-100,000 viral copies/mL with a lower limit of quantification (LLOQ) of 200 copies/mL. Results below LLOQ were considered undetectable. Confirmed undetectable plasma CMV DNA within 6 weeks was defined as 2 consecutive post-baseline, on-treatment undetectable results separated by \>/= 5 days (assessed by the central laboratory). Samples were collected on Days 1 and 8, weekly during Weeks 2-6, and once in Weeks 8, 10, 12, 16, 20, 24 (treatment) and Weeks 1, 4, 8, 12 (follow-up). Permissible assessment windows were: Days 8-15 +/- 1 day; Weeks 3-4 +/- 2 days; Weeks 5-6 +/- 3 days; Weeks 8-12 +/- 4 days; Weeks 16-24 +/- 7 days (treatment) and Weeks 1-4 +/- 2 days; Weeks 8-12 +/- 4 days (follow-up).
- Secondary Outcome Measures
Name Time Method Time to First Confirmed Undetectable Plasma CMV DNA Within 6 Weeks and at Any Time During The Study 6 weeks after start of treatment, within 36 weeks of start of treatment Blood samples were collected at the study sites, processed to plasma aliquots, and sent to the central laboratory for quantitative CMV DNA polymerase chain reaction (PCR) testing. Plasma samples were assayed for CMV concentration using a qualified PCR method. The time to event was defined as the time from first dose of study drug to first undetectable plasma CMV DNA within 6 weeks and at any time during the study, defined as the date of the first of at least 2 consecutive post-baseline, on-treatment undetectable results (\<200 copies/mL) separated by at least 5 days; as assessed by the central laboratory. The median values are Kaplan-Meier estimates.
Time to CMV Recurrence 36 weeks Blood samples were collected at the study sites, processed to plasma aliquots, and sent to the central laboratory for quantitative CMV DNA polymerase chain reaction (PCR) testing. Plasma samples were assayed for CMV concentration using a qualified PCR method. The time to event was defined as the time of the first of at least 2 consecutive samples, separated by at least 5 days, with detectable plasma CMV DNA after achievement of undetectable plasma CMV DNA in at least 2 consecutive samples, separated by at least 5 days, at any time after Day 1; as assessed by the central laboratory. Participants assessed for recurrence (n= 29, 27, 30) are the subset of the ITT-S who had at least 2 consecutive undetectable plasma CMV DNA results separated by at least 5 days, including early withdrawn qualified subjects. The median values are Kaplan-Meier estimates.
Area Under The Plasma Concentration Versus Time Curve From The Time of Dosing to The Last Measurable Concentration (AUClast) of Maribavir pre-dose and 1, 2, 3, 4, 6, 8, and 12 hours post-dose on Day 8 and the Week 4 visit For the subset of participants who had pharmacokinetic (PK) profiling performed, non-compartmental PK analyses were used to determine Cmax, time to Cmax (tmax), time of last non-zero concentration (tlast), area under the plasma concentration versus time curve from the time of dosing to the last measurable concentration (AUClast), and half-life (t½). Values below the LLOQ post-baseline were replaced with a value of 0 ug/mL. Values below the LLOQ at baseline were replaced with zero as it was assumed that subjects had no levels of maribavir at baseline. At the designated timepoints, the PK sample was obtained 2-4 hours after the dose of study drug; for subjects who were inpatients, a pre-dose PK sample also was collected. These samples were not required at Day 8 and Week 4 for subjects who had PK profiles performed on those days.
Number of Participants With CMV Recurrence 36 weeks Blood samples were collected at the study sites, processed to plasma aliquots, and sent to the central laboratory for quantitative CMV DNA polymerase chain reaction (PCR) testing. Plasma samples were assayed for CMV concentration using a qualified PCR method. CMV recurrence was defined as achievement of undetectable plasma CMV DNA at any time after Day 1 in at least 2 consecutive samples separated by at least 5 days, followed by detectable plasma CMV DNA in at least 2 consecutive samples separated by at least 5 days (assessed by the central laboratory). For the analyses of CMV recurrence, the first of 2 consecutive confirmed undetectable plasma CMV DNA results had to be on-treatment. CMV DNA PCR values of ≥200 copies/mL were considered detectable. Participants assessed for recurrence (n= 29, 27, 30) are the subset of the ITT-S who had at least 2 consecutive undetectable plasma CMV DNA results separated by at least 5 days, including early withdrawn qualified subjects.
Half-Life (T½) of Maribavir pre-dose and 1, 2, 3, 4, 6, 8, and 12 hours post-dose on Day 8 and the Week 4 visit For the subset of participants who had pharmacokinetic (PK) profiling performed, non-compartmental PK analyses were used to determine Cmax, time to Cmax (tmax), time of last non-zero concentration (tlast), area under the plasma concentration versus time curve from the time of dosing to the last measurable concentration (AUClast), and half-life (t½). Values below the LLOQ post-baseline were replaced with a value of 0 ug/mL. Values below the LLOQ at baseline were replaced with zero as it was assumed that subjects had no levels of maribavir at baseline. At the designated timepoints, the PK sample was obtained 2-4 hours after the dose of study drug; for subjects who were inpatients, a pre-dose PK sample also was collected. These samples were not required at Day 8 and Week 4 for subjects who had PK profiles performed on those days.
Maximum Concentration (Cmax) of Maribavir pre-dose and 1, 2, 3, 4, 6, 8, and 12 hours post-dose on Day 8 and the Week 4 visit For the subset of participants who had pharmacokinetic (PK) profiling performed, non-compartmental PK analyses were used to determine Cmax, time to Cmax (tmax), time of last non-zero concentration (tlast), area under the plasma concentration versus time curve from the time of dosing to the last measurable concentration (AUClast), and half-life (t½). Values below the LLOQ post-baseline were replaced with a value of 0 ug/mL. Values below the LLOQ at baseline were replaced with zero as it was assumed that subjects had no levels of maribavir at baseline. At the designated timepoints, the PK sample was obtained 2-4 hours after the dose of study drug; for subjects who were inpatients, a pre-dose PK sample also was collected. These samples were not required at Day 8 and Week 4 for subjects who had PK profiles performed on those days.
Time of Last Non-Zero Concentration (Tlast) of Maribavir pre-dose and 1, 2, 3, 4, 6, 8, and 12 hours post-dose on Day 8 and the Week 4 visit For the subset of participants who had pharmacokinetic (PK) profiling performed, non-compartmental PK analyses were used to determine Cmax, time to Cmax (tmax), time of last non-zero concentration (tlast), area under the plasma concentration versus time curve from the time of dosing to the last measurable concentration (AUClast), and half-life (t½). Values below the LLOQ post-baseline were replaced with a value of 0 ug/mL. Values below the LLOQ at baseline were replaced with zero as it was assumed that subjects had no levels of maribavir at baseline. At the designated timepoints, the PK sample was obtained 2-4 hours after the dose of study drug; for subjects who were inpatients, a pre-dose PK sample also was collected. These samples were not required at Day 8 and Week 4 for subjects who had PK profiles performed on those days.
Time to Maximum Concentration (Tmax) of Maribavir pre-dose and 1, 2, 3, 4, 6, 8, and 12 hours post-dose on Day 8 and the Week 4 visit For the subset of participants who had pharmacokinetic (PK) profiling performed, non-compartmental PK analyses were used to determine Cmax, time to Cmax (tmax), time of last non-zero concentration (tlast), area under the plasma concentration versus time curve from the time of dosing to the last measurable concentration (AUClast), and half-life (t½). Values below the LLOQ post-baseline were replaced with a value of 0 ug/mL. Values below the LLOQ at baseline were replaced with zero as it was assumed that subjects had no levels of maribavir at baseline. At the designated timepoints, the PK sample was obtained 2-4 hours after the dose of study drug; for subjects who were inpatients, a pre-dose PK sample also was collected. These samples were not required at Day 8 and Week 4 for subjects who had PK profiles performed on those days.
Trial Locations
- Locations (32)
University of Chicago
🇺🇸Chicago, Illinois, United States
Brigham and Women's Hospital
🇺🇸Boston, Massachusetts, United States
Emory University
🇺🇸Atlanta, Georgia, United States
Johns Hopkins Hospital
🇺🇸Baltimore, Maryland, United States
Columbia University
🇺🇸New York, New York, United States
University of Nebraska
🇺🇸Omaha, Nebraska, United States
University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
Nationwide Children's Hospital
🇺🇸Columbus, Ohio, United States
Cleveland Clinic Foundation
🇺🇸Cleveland, Ohio, United States
University of Minnesota Medical Center
🇺🇸Minneapolis, Minnesota, United States
University of Washington
🇺🇸Seattle, Washington, United States
Methodist Healthcare System
🇺🇸San Antonio, Texas, United States
Fred Hutchinson Cancer Research Center
🇺🇸Seattle, Washington, United States
University of Utah
🇺🇸Salt Lake City, Utah, United States
Vanderbilt Medical Center
🇺🇸Nashville, Tennessee, United States
Ochsner Clinic Foundation
🇺🇸New Orleans, Louisiana, United States
UCLA Medical Center
🇺🇸Los Angeles, California, United States
Stanford University Medical Center
🇺🇸Stanford, California, United States
University of Colorado
🇺🇸Denver, Colorado, United States
Tampa General Hospital
🇺🇸Tampa, Florida, United States
Yale University
🇺🇸New Haven, Connecticut, United States
University of Florida
🇺🇸Gainesville, Florida, United States
Northwestern University Medical Center
🇺🇸Chicago, Illinois, United States
University of Massachusetts
🇺🇸Worcester, Massachusetts, United States
University of Michigan
🇺🇸Ann Arbor, Michigan, United States
Henry Ford Health Care System
🇺🇸Detroit, Michigan, United States
Albert Einstein Medical Center
🇺🇸Philadelphia, Pennsylvania, United States
University of Pittsburg
🇺🇸Pittsburgh, Pennsylvania, United States
Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
Memorial Sloan-Kettering Cancer Center
🇺🇸New York, New York, United States
Wake Forest Medical Center
🇺🇸Winston-Salem, North Carolina, United States