A Safety Assessment of Oral Letermovir in Infants With Symptomatic Congenital Cytomegalovirus
Status:
Not yet recruiting
Trial end date:
2025-03-04
Target enrollment:
Participant gender:
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.
Phase:
Phase 1
Details
Lead Sponsor:
National Institute of Allergy and Infectious Diseases (NIAID)