Ignite Creation Date:
2024-05-06 @ 7:44 PM
Last Modification Date:
2024-10-26 @ 3:13 PM
Study NCT ID:
NCT06118515
Status:
RECRUITING
Last Update Posted:
2023-11-07
First Post:
2023-11-01
Brief Title:
A Safety Assessment of Oral Letermovir in Infants With Symptomatic Congenital Cytomegalovirus
Sponsor:
National Institute of Allergy and Infectious Diseases NIAID
Organization:
National Institute of Allergy and Infectious Diseases NIAID
Study Overview
Official Title:
A Phase I Pharmacokinetic and Safety Assessment of Oral Letermovir in Infants With Symptomatic Congenital Cytomegalovirus Disease
Status:
RECRUITING
Status Verified Date:
2024-06
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This is a Phase 1 single-arm open-label study of letermovir in neonates with symptomatic congenital Cytomegalovirus CMV disease There will be two groups enrolled Group 1 will be comprised of 4 subjects Following documentation study inclusion and signing of informed consent Group 1 subjects will receive one dose of oral letermovir Study Day 0 using the dose bands A full pharmacokinetics PK profile will then be obtained over the next 24 hours and blood specimens will be shipped immediately to the University of Alabama at Birmingham UAB Pharmacokinetic Lab and processed in real time Within 7 days pharmacokinetics PK results will be conveyed to the study site If the Area Under the Curve AUC24 is 100000 ngxhrmL see footnote a in Table 1 the subject will initiate a 14-day course of once-daily oral letermovir at the same dose as utilized on Dose Finding Day This duration of letermovir therapy was selected based upon our earlier observation in this population that patients with symptomatic congenital Cytomegalovirus CMV disease who achieve viral suppression to 25 log by day 14 of valganciclovir therapy and then maintain it over the next 4 months are statistically more likely to have improved hearing across the first two years of life 22 If the observed letermovir exposure of the subject is 100000 ngxhrmL the once-daily oral letermovir dose that will be used will be adjusted down in 25 mg increments Oral valganciclovir 16 mgkgdose BID will begin within the first month of life as standard of care initiation of valganciclovir can be concomitant with or prior to initiation of the 14-day course of letermovir but will not start before obtaining the pharmacokinetics PK specimens following the single dose of letermovir on the Dose Finding Day This is similar to the intensification approach that has been evaluated in the management of patients infected with human immunodeficiency virus 23-25 The day that the 14-day course of letermovir begins for Group 1 subjects will be known as Study Day 1 Serial blood samples will be obtained on Study Days 1 5 10 and 14 for safety chemistry and hematology labs and for Cytomegalovirus CMV viral loads Cytomegalovirus CMV viral load will be followed as well on Study Days 21 and 42 to assess for rebound in Cytomegalovirus CMV following cessation of letermovir treatment on Study Day 14 Saliva and urine viral loads will be followed at these timepoint as well Full pharmacokinetics PK profiles for both letermovir and ganciclovir will be obtained on Study Day 10 In addition sparse pharmacokinetics PK sampling will be obtained on Study Days 1 5 and 14 Adverse events will be assessed at each study visit during treatment and at Study Days 21 and 42 4 weeks after the last study drug dose Subjects then will continue on oral valganciclovir as routine clinical care to complete an anticipated 6 month duration of total therapy The primary Objective is to determine the systemic exposure AUC24 of letermovir following administration of oral letermovir granules in infants with symptomatic congenital CMV disease
Detailed Description:
This is a Phase 1 single-arm open-label study of letermovir in neonates with symptomatic congenital Cytomegalovirus CMV disease There will be two groups enrolled Group 1 will be comprised of 4 subjects Following documentation study inclusion and signing of informed consent Group 1 subjects will receive one dose of oral letermovir Study Day 0 using the dose bands A full pharmacokinetics PK profile will then be obtained over the next 24 hours and blood specimens will be shipped immediately to the University of Alabama at Birmingham UAB Pharmacokinetic Lab and processed in real time Within 7 days pharmacokinetics PK results will be conveyed to the study site If the Area Under the Curve AUC24 is 100000 ngxhrmL see footnote a in Table 1 the subject will initiate a 14-day course of once-daily oral letermovir at the same dose as utilized on the Dose Finding Day This duration of letermovir therapy was selected based upon our earlier observation in this population that patients with symptomatic congenital Cytomegalovirus CMV disease who achieve viral suppression to 25 log by day 14 of valganciclovir therapy and then maintain it over the next 4 months are statistically more likely to have improved hearing across the first two years of life 22 If the observed letermovir exposure of the subject is 100000 ngxhrmL the once-daily oral letermovir dose that will be used will be adjusted down in 25 mg increments Oral valganciclovir 16 mgkgdose BID will begin within the first month of life as standard of care initiation of valganciclovir can be concomitant with or prior to initiation of the 14-day course of letermovir but will not start before obtaining the pharmacokinetics PK specimens following the single dose of letermovir on the Dose Finding Day This is similar to the intensification approach that has been evaluated in the management of patients infected with human immunodeficiency virus 23-25 The day that the 14-day course of letermovir begins for Group 1 subjects will be known as Study Day 1 Serial blood samples will be obtained on Study Days 1 5 10 and 14 for safety chemistry and hematology labs and for Cytomegalovirus CMV viral loads Cytomegalovirus CMV viral load will be followed as well on Study Days 21 and 42 to assess for rebound in Cytomegalovirus CMV following cessation of letermovir treatment on Study Day 14 Saliva and urine viral loads will be followed at these timepoint as well Full pharmacokinetics PK profiles for both letermovir and ganciclovir will be obtained on Study Day 10 In addition sparse pharmacokinetics PK sampling will be obtained on Study Days 1 5 and 14 Adverse events will be assessed at each study visit during treatment and at Study Days 21 and 42 4 weeks after the last study drug dose Subjects then will continue on oral valganciclovir as routine clinical care to complete an anticipated 6 month duration of total therapy Following enrollment of the 4 subjects in Group 1 the Safety Monitoring Committee SMC will review all safety and pharmacokinetic data If no halting rules are met and no other safety concerns are identified then additional subjects will be enrolled in Group 2 Subjects in Group 2 will initiate a 14-day course of once-daily oral letermovir using the dose bands listed in Table 1 at the same time that oral valganciclovir 16 mgkgdose BID is initiated as standard of care initiation of valganciclovir can be concomitant with or prior to initiation of the 14-day course of letermovir If the median of observed letermovir exposures of subjects in Group 1 is below 34400 ngxhrmL or above 100000 ngxhrmL then the subjects enrolled in Group 2 will receive once-daily oral letermovir at a dose that has been adjusted upward or downward in 25 mg increments The day that the 14-day course of letermovir begins for Group 2 will be known as Study Day 1 Serial blood samples will be obtained on Study Days 1 5 10 and 14 for safety chemistry and hematology labs and for Cytomegalovirus CMV viral loads Cytomegalovirus CMV viral load will be followed as well on Study Days 21 and 42 to assess for rebound in Cytomegalovirus CMV following cessation of letermovir treatment on Study Day 14 Saliva and urine viral loads will be followed at these timepoint as well Full pharmacokinetics PK profiles for both letermovir and ganciclovir will be obtained on Study Day 10 In addition sparse pharmacokinetics PK sampling will be obtained on Study Days 1 5 and 14 Adverse events will be assessed at each study visit during treatment and at Study Days 21 and 42 4 weeks after the last study drug dose Subjects then will continue on oral valganciclovir as routine clinical care to complete an anticipated 6 month duration of total therapy The primary Objective is to determine the systemic exposure AUC24 of letermovir following administration of oral letermovir granules in infants with symptomatic congenital CMV disease the secondary objectives are 1 To determine the other pharmacokinetic parameters of letermovir following administration of oral letermovir granules in infants with symptomatic congenital CMV disease 2 To evaluate the safety of letermovir oral granules in infants
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
None