Safety assessment of oral letermovir in infants with congenital CMV infection

A Phase I Pharmacokinetic and Safety Assessment of Oral Letermovir in Infants With Symptomatic Congenital Cytomegalovirus Disease

This study is testing if the medication letermovir is safe for infants with congenital CMV infection and figuring out the right dose for them.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 12 (estimated)
• Ages: 0 Days to 90 Days
• Sex: All
• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) (NIH)
• Locations: 10 sites (Birmingham, Alabama and 9 other locations)
• Trial ID: NCT06118515 on ClinicalTrials.gov

What this trial studies

This Phase 1 open-label study evaluates the safety and pharmacokinetics of oral letermovir in neonates diagnosed with symptomatic congenital Cytomegalovirus (CMV) disease. The study involves two groups, with the first group receiving a single dose of letermovir followed by a 24-hour monitoring period to assess drug levels in the blood. If the pharmacokinetic results indicate adequate drug exposure, participants will then receive a 14-day course of letermovir. The study aims to determine the appropriate dosing and safety profile of letermovir in this vulnerable population.

Who should consider this trial

Good fit: Ideal candidates for this study are infants aged 90 days or younger with confirmed symptomatic congenital CMV disease.

Not a fit: Patients who are older than 90 days or do not have symptomatic congenital CMV disease will not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a new treatment option that improves outcomes for infants suffering from symptomatic congenital CMV infection.

How similar studies have performed: While this approach is novel in this specific population, previous studies have shown promise in treating CMV infections with antiviral therapies.

Eligibility criteria

Inclusion Criteria:

1. Signed informed consent from parent(s) or legal guardian(s)
2. Cytomegalovirus (CMV) confirmation by culture, shell vial, or Polymerase Chain Reaction (PCR) tests from a specimen obtained at \</= 30 days of life from saliva, blood, or urine
3. Symptomatic congenital CMV disease\*
4. Age at study enrollment:

   1. \</= 83 days for Group 1 subjects\*\*
   2. \</= 90 days for Group 2 subjects
5. Weight at study enrollment 2.6 kg to \< 8.0 kg
6. Gestational age \>/= 32 weeks at birth
7. Intention by patient's physician to clinically treat infant with oral valganciclovir for 6 months for symptomatic congenital CMV disease

   * Manifested by one or more of the following: thrombocytopenia; petechiae; hepatomegaly; splenomegaly; intrauterine growth restriction; hepatitis; or Central Nervous System (CNS) involvement such as microcephaly, radiographic abnormalities indicative of CMV CNS disease, abnormal cerebrospinal fluid (CSF) indices for age, chorioretinitis, hearing deficits as detected by formal brainstem evoked response, and/or positive CMV Polymerase Chain Reaction (PCR) from CSF \*\*Group 1 subjects must enroll and receive the Dose Finding Day dose of letermovir on or before 83 days of life so that oral valganciclovir can be started prior to 12 weeks 6 days (which is 90 days) of life, as is standard of care. For this study, the date of birth is counted as day of life 0

Exclusion Criteria:

1. Imminent demise
2. Infants known to be born to women who are HIV positive (but HIV testing is not required for study entry)
3. Current receipt of other investigational drugs
4. Grade 3 or 4 alanine aminotransferase (ALT) utilizing Division of AIDS (DAIDS) Toxicity Table
5. Grade 3 or 4 total bilirubin utilizing DAIDS Toxicity Table
6. Gastrointestinal abnormality which might preclude absorption of an oral medication (e.g., a history of necrotizing enterocolitis)
7. Anticipated concomitant administration of carbamazepine (Tegretol), nafcillin, phenobarbital, or phenytoin (Dilantin) during the period of study drug administration

Where this trial is running

Birmingham, Alabama and 9 other locations

• Children's of Alabama Child Health Research Unit (CHRU) — Birmingham, Alabama, United States (Recruiting)
• Children's National Medical Center - Sheikh Zayed Campus - Infectious Disease — Washington D.C., District of Columbia, United States (Withdrawn)
• Emory University School of Medicine — Atlanta, Georgia, United States (Recruiting)
• University of Louisville School of Medicine - Norton Children's Hospital - Infectious Diseases — Louisville, Kentucky, United States (Withdrawn)
• Louisiana State University Health Shreveport - Infectious Diseases — Shreveport, Louisiana, United States (Withdrawn)
• University of Minnesota - Pediatric Infectious Disease — Minneapolis, Minnesota, United States (Withdrawn)
• SUNY Upstate Medical University Hospital - Pediatrics — Syracuse, New York, United States (Withdrawn)
• Nationwide Children's Hosp.-Neonatology-Ctr. for Perinatal Rsrch. — Columbus, Ohio, United States (Withdrawn)
• University of Texas Southwestern Medical Center - Pediatrics — Dallas, Texas, United States (Withdrawn)
• Medical College of Wisconsin — Milwaukee, Wisconsin, United States (Recruiting)

Study contacts

• Study coordinator: David W. Kimberlin

Conditions Congenital Cytomegalovirus Infection; Congenital Cytomegalovirus Disease; Infants; Letermovir; Pharmacokinetic; Phase 1