Prenatal Treatment of Congenital Cytomegalovirus Infection With Letermovir Versus Valaciclovir

NCT05446571 | Recruiting Phase 3 DMC

• 2 other identifiers: APHP180592_step22020-002924-35
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 1

Brief Summary

The investigators' hypothesis is that maternal treatment with Letermovir will inhibit fetal CMV replication better than Valaciclovir in infected fetuses and lead to a higher proportion of negative CMV PCR at birth in neonatal blood collected in the first day of life or in cord blood in case of termination of pregnancy (TOP). The main objective is to demonstrate that Letermovir administered to women carrying a CMV infected fetus following a maternal infection of the first trimester increases the proportion of neonates with a negative CMV PCR in neonatal blood collected in the first day of life or in cord blood in case of termination of pregnancy (TOP) compared to Valaciclovir. In each group , the proportion of asymptomatic neonates and the number and type of long-term sequelae at 2 years will also be assessed and compared.

Conditions

Pregnant Women; CMV Infected Fetuses

Keywords

cytomegalovirus; pregnant women

Outcome Measures

Primary Outcomes (2)

• CMV PCR in neonatal blood collected

  Negative CMV PCR (\<500 IU/ml) in neonatal blood

  in the first day of life

• CMV PCR in neonatal blood collected

  Negative CMV PCR (\<500 IU/ml) in cord blood

  At Termination of pregnancy

Secondary Outcomes (38)

• Number of asymptomatic neonates

  in the first day of life

• Birthweight

  at birth

• placental weight

  at birth

• number of long-term sequelae

  at 2 years of life

• type of long-term sequelae

  at 2 years of life

Study Arms (2)

Letermovir

EXPERIMENTAL

Maternal daily administration of letermovir + placebo of valaciclovir

Drug: Letermovir

Valaciclovir

ACTIVE COMPARATOR

Maternal daily administration of valaciclovir + placebo of letermovir

Drug: Valacyclovir

Interventions

Letermovir DRUG

Maternal daily administration of 240 milligrams of letermovir (1x240 mg-tablets) up-until delivery or TOP Placebo of Valaciclovir ; daily administration of 8 grams of valaciclovir (2 g (4 x500 mg-tablets) every 6 hours) up-until delivery or TOP

Letermovir

Valacyclovir DRUG

Maternal daily administration of 8 grams of valaciclovir (2 g (4 x500 mg-tablets) every 6 hours) up-until delivery or TOP Placebo of letermovir : (1x240 mg-tablets) up-until delivery or TOP

Valaciclovir

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead
• URC-CIC Paris Descartes Necker Cochin: collaborator

Study Sites (1)

Hopital Necker - Enfants malades

Paris, 75015, France

RECRUITING

MeSH Terms

Interventions

letermovir; Valacyclovir

Intervention Hierarchy (Ancestors)

Acyclovir; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Marianne LERUEZ-VILLE, MD, PhD

  Virology laboratory- reference national Lab for CMV infection -Hôpital Necker-Enfants malades, Paris

  STUDY CHAIR

Central Study Contacts

Yves VILLE, MD, PhD

CONTACT

+33 1 71 19 63 32; ville.yves@gmail.com

Aminata TRAORE

CONTACT

+33 1 48 19 27 34; aminata.traore6@aphp.fr

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 7, 2022
• First Posted: July 6, 2022
• Study Start: October 20, 2023
• Primary Completion (Estimated): August 1, 2029
• Study Completion (Estimated): August 1, 2029
• Last Updated: March 31, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)