The main aim of this study is to find out the safety, tolerability and pharmacokinetics (PK) of maribavir for the treatment of CMV infection in children and teenagers after HSCT or SOT and to identify the optimal dose of maribavir using a 200 milligrams (mg) tablet formulation or powder for oral suspension. The participants will be treated with maribavir for 8 weeks. Participants need to visit their doctor during 12-week follow-up period.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
80
Participants will receive maribavir.
University of Nebraska Medical Center -985400 Nebraska Medical Center
Omaha, Nebraska, United States
RECRUITINGCincinnati Children's Hospital Medical Center - PIN
Cincinnati, Ohio, United States
RECRUITINGCook Children's Health Care System
Fort Worth, Texas, United States
RECRUITINGUniversity of Texas MD Anderson Cancer Center - 1515 Holcombe Blvd
Houston, Texas, United States
Maximum Observed Plasma Concentration (Cmax) of Maribavir
Cmax of maribavir will be evaluated.
Time frame: Pre-dose; 0.5, 1.5, 3, 4, 6, and 8 hours post-dose on Day 7 (Week 1)
Time to Maximum Observed Concentration (Tmax) of Maribavir
Tmax of maribavir will be evaluated.
Time frame: Pre-dose; 0.5, 1.5, 3, 4, 6, and 8 hours post-dose on Day 7 (Week 1)
Minimum Plasma Concentration (Cmin) of Maribavir
Cmin of maribavir will be evaluated.
Time frame: Pre-dose; (0.5, 1.5, 3, 4, 6, and 8 hours post-dose) on Day 7 (Week 1); Pre-dose on Day 28 (Week 4); Pre-dose; (2 to 4 hours post-dose) on Day 56 (Week 8)
Area Under the Plasma Concentration-Time Curve Over the 1 Dosing Interval of 12 Hours at Steady State (AUC0-tau) of Maribavir
AUC0-tau of maribavir will be evaluated.
Time frame: Pre-dose; 0.5, 1.5, 3, 4, 6, and 8 hours post-dose on Day 7 (Week 1)
Half-Life (t1/2) of Maribavir
t1/2 of maribavir will be evaluated.
Time frame: Pre-dose; 0.5, 1.5, 3, 4, 6, and 8 hours post-dose on Day 7 (Week 1)
Terminal Elimination Rate Constant (lambdaz) of Maribavir
Lambdaz of maribavir will be evaluated.
Time frame: Pre-dose; 0.5, 1.5, 3, 4, 6, and 8 hours post-dose on Day 7 (Week 1)
Apparent Volume of Distribution (Vz/F) of Maribavir
Vz/F of maribavir will be evaluated.
Time frame: Pre-dose; 0.5, 1.5, 3, 4, 6, and 8 hours post-dose on Day 7 (Week 1)
Apparent Oral Clearance (CL/F) of Maribavir
CL/F of maribavir will be evaluated.
Time frame: Pre-dose; 0.5, 1.5, 3, 4, 6, and 8 hours post-dose on Day 7 (Week 1)
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
An AE is any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and that does not necessarily be considered related to investigational product. SAE is any untoward medical occurrence (whether considered related to investigational product or not) that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital abnormality or birth defect, or is an important medical event.
Time frame: From start of study drug administration up to follow-up (Week 20)
Percentage of Participants With Confirmed CMV viremia Clearance at Week 8
Confirmed CMV viremia clearance is defined as plasma CMV DNA concentration below the lower limit of quantification (LLOQ) at a central specialty laboratory, in 2 consecutive postbaseline samples, separated by at least 5 days at Week 8 regardless of the length of study treatment. Percentage of participants with confirmed CMV viremia clearance at Week 8 will be reported.
Time frame: At Week 8
Percentage of Participants who Achieve Maintenance of Confirmed CMV Viremia Clearance and Symptom Control at Week 8 Through Weeks 12, 16 and 20
Confirmed CMV viremia clearance is defined as plasma CMV DNA concentration below the lower LLOQ at a central specialty laboratory, in 2 consecutive postbaseline samples, separated by at least 5 days regardless of the length of study treatment. CMV infection symptom control is defined as resolution or improvement of tissue invasive disease or CMV syndrome for symptomatic participants at baseline, or no new symptoms for asymptomatic participants at baseline. Percentage of participants who achieve maintenance of confirmed CMV viremia clearance and symptom control at Week 8 through Weeks 12, 16 and 20 will be reported.
Time frame: At Week 8 through Weeks 12, 16, and 20
Percentage of Participants With Confirmed Recurrence of CMV Viremia on Study Treatment and Off Study Treatment
Confirmed recurrence of CMV viremia is defined as plasma CMV DNA concentration greater than or equal to (\>=) LLOQ when assessed in 2 consecutive plasma samples at least 5 days apart, after achieving confirmed viremia clearance. Percentage of participants with confirmed recurrence of viremia on study treatment and off study treatment will be reported.
Time frame: Up to Week 20
Time to First Confirmed Viremia Clearance
Confirmed CMV viremia clearance is defined as plasma CMV DNA concentration below the lower LLOQ when assessed at a central specialty laboratory, in 2 consecutive postbaseline samples, separated by at least 5 days. Time to first confirmed viremia clearance at any time during the study will be summarized using the Kaplan-Meier method.
Time frame: Up to Week 20
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Sydney Children's Hospital
Randwick, New South Wales, Australia
RECRUITINGQueensland Children's Hospital
South Brisbane, Queensland, Australia
RECRUITINGRoyal Children's Hospital Melbourne - PIN
Parkville, Victoria, Australia
RECRUITINGPerth Children's Hospital
Nedlands, Western Australia, Australia
RECRUITINGHôpital Universitaire des Enfants Reine Fabiola (HUDERF)
Brussels, Brussels Capital, Belgium
RECRUITINGCliniques Universitaires Saint-Luc
Woluwe-Saint-Lambert, Brussels Capital, Belgium
RECRUITING...and 37 more locations
Percentage of Participants With Confirmed Recurrence of CMV Viremia Treated With Alternative Anti-CMV Treatment During 12-Week Follow-up Period in Participants With Confirmed Viremia Clearance at Week 8
Confirmed recurrence of CMV viremia is defined as plasma CMV DNA concentration \>= LLOQ when assessed in 2 consecutive plasma samples at least 5 days apart, after achieving confirmed viremia clearance. Percentage of participants with confirmed recurrence of CMV viremia treated with alternative anti-CMV treatment in the 12-Week follow-up period in participants with confirmed viremia clearance at Week 8 will be reported.
Time frame: From Week 8 through Week 20
Change From Baseline in Log10 Plasma CMV Deoxyribonucleic Acid (DNA) Load
Change from baseline in log10 plasma CMV DNA on study after receiving study treatment by study week will be reported.
Time frame: Baseline up to Week 20
Number of Participants who Develop CMV Resistance to Maribavir
CMV DNA genotyping will be performed for the UL97, UL54, UL56, and UL27 genes known to confer resistance to conventional anti-CMV therapies or Maribavir. Number of participants who developed post-baseline CMV resistance to maribavir up to Week 12 will be reported.
Time frame: Up to Week 12
Summary Scores for Palatability Assessment of Maribavir
Palatability (taste, feel, smell, ease of swallowing and after-taste) is being measured using a 5-point facial hedonic scale correlated with a 100-point linear visual analogue scale (VAS) ranges from 0: very bad to 100: very good. Scores will be summarized descriptively at Weeks 1, 4 and 8.
Time frame: At Weeks 1, 4, and 8