Clinical Trial Details
— Status: Not yet recruiting
Administrative data
| NCT number |
NCT06118515 |
| Other study ID # |
21-0027 |
| Secondary ID |
|
| Status |
Not yet recruiting |
| Phase |
Phase 1
|
| First received |
|
| Last updated |
|
| Start date |
November 16, 2023 |
| Est. completion date |
March 4, 2025 |
Study information
| Verified date |
August 2023 |
| Source |
National Institute of Allergy and Infectious Diseases (NIAID) |
| Contact |
David W. Kimberlin |
| Phone |
12059966097 |
| Email |
dkimberlin[@]peds.uab.edu |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial 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 = 100,000 ngxhr/mL (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 Study Day 0. 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 = 2.5 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 > 100,000
ngxhr/mL, the once-daily oral letermovir dose that will be used will be adjusted down in 2.5
mg increments. Oral valganciclovir (16 mg/kg/dose 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 Study Day 0). 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.
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 = 100,000 ngxhr/mL (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 Study Day 0. 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 = 2.5 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 > 100,000
ngxhr/mL, the once-daily oral letermovir dose that will be used will be adjusted down in 2.5
mg increments. Oral valganciclovir (16 mg/kg/dose 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 Study Day 0). 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 mg/kg/dose 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 34,400 ngxhr/mL (or above 100,000 ngxhr/mL), then the subjects enrolled in
Group 2 will receive once-daily oral letermovir at a dose that has been adjusted upward (or
downward) in 2.5 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.
