Treating pregnant women with CMV-infected fetuses using Letermovir or Valaciclovir

Prenatal Treatment of Congenital Cytomegalovirus Infection With Letermovir Randomized Against Valaciclovir (Step 2)

This study tests whether the medications Letermovir or Valaciclovir are better at treating pregnant women whose babies have a cytomegalovirus infection to see which one leads to healthier outcomes for the babies at birth and later on.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 46 (estimated)
• Ages: 18 Years and up
• Sex: Female
• Sponsor: Assistance Publique - Hôpitaux de Paris (Academic / other)
• Locations: 1 site (Paris)
• Trial ID: NCT05446571 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to compare the effectiveness of Letermovir and Valaciclovir in treating pregnant women whose fetuses are infected with cytomegalovirus (CMV). The study will assess whether Letermovir can better inhibit fetal CMV replication compared to Valaciclovir, leading to a higher rate of negative CMV PCR results at birth. Additionally, the trial will evaluate the long-term outcomes of neonates, including the incidence of neurological deficiencies and hearing loss, at two years of age. Participants will be monitored for compliance with study visits and procedures throughout the trial.

Who should consider this trial

Good fit: Ideal candidates are pregnant women aged 18 and older who have a confirmed CMV infection in the first trimester and an infected fetus without severe cerebral ultrasound features.

Not a fit: Patients who may not benefit include those with maternal CMV infection after 15 weeks or those with severe fetal brain abnormalities.

Why it matters

Potential benefit: If successful, this treatment could significantly reduce the incidence of long-term neurological issues in neonates born to mothers with CMV infections.

How similar studies have performed: Previous studies have shown modest benefits of antiviral treatments in symptomatic neonates, but this approach using Letermovir is novel and untested in this specific context.

Eligibility criteria

Inclusion Criteria:

* Pregnant woman ≥ 18 years old,
* CMV infection in the 1st trimester
* with an infected fetus at 15 -28 weeks (positive CMV PCR in the amniotic fluid) With a fetus presenting without any severe cerebral ultrasound feature (ventriculomegaly ≥15 mm, hydrocephalus, periventricular hyperechogenicity, microcephaly\<-3SD, vermian hypoplasia, porencephaly, lissencephaly, corpus callosum dysgenesis, cystic leukomalacia)
* affiliation to a social security regime//health insurance
* Given consent for the study
* Patient must be able and willing to comply with study visits and procedures

Exclusion Criteria

* Participation to another interventional drug trial (category 1)
* Subject protected by law under guardianship or curatorship
* Maternal CMV infection after 15 weeks'
* Creatinine clearance \<50 ml/mn/1,73m²
* Liver insufficiency (Child Pugh grade C), AST, ALT 5 x ULN, bilirubin 2 x ULN.
* Woman with known allergy to Letermovir or Valaciclovir
* Contraindication for the administration of Letermovir and Valaciclovir listed in the SmPC of Prevymis® and Zelitrex®
* Women with hypersensitivity to aciclovir
* Concomitant administration of St John's wort
* Woman treated by pimozide, ergot alkaloids, dabigatran, atorvastatin, simvastatin, rosuvastatin, pitavastatin or cyclosporin.
* Woman with hereditary intolerance to galactose, with lactose lapp deficiency, glucose or galactose malabsorption syndrome

Where this trial is running

Paris

• Hopital Necker - Enfants malades — Paris, France (Recruiting)

Study contacts

• Study coordinator: Yves VILLE, MD, PhD

Conditions Pregnant Women; CMV Infected Fetuses; cytomegalovirus; pregnant women