LETERMOVIR for Congenital cytomegalovirus infection | Maternal cytomegalovirus infection

Inclusion criteria

• {"criterion_text":"- Step1:\n- Pregnant woman ≥ 18 years old\n- in her second trimester of pregnancy\n- undergoing TOP for any fetal abnormality\n- no evidence of placental dysfunction.\n- affiliation to a social security regime//health insurance\n- given consent for the study.\n- patient must be able and willing to comply with study visits and procedures\n- Step2:\n- Pregnant woman ≥ 18 years old,\n- CMV infection in the 1st trimester\n- with an infected fetus at 15 -28 weeks (positive CMV PCR in the amniotic fluid)\n- With a fetus presenting without any severe cerebral ultrasound feature (ventriculomegaly ≥15 mm, hydrocephalus, periventricular hyperechogenicity, microcephaly<-3SD, vermian hypoplasia, porencephaly, lisencephaly, corpus callosum dysgenesis, cystic leukomalacia, Mega-cisterna magna >10 mm)\n- affiliation to a social security regime//health insurance\n- Given consent for the study\n- Patient must be able and willing to comply with study visits and procedures"}

Exclusion criteria

• {"criterion_text":"- Step1:\n- Participation to another interventional drug trial (category 1)\n- Subject protected by law under guardianship or curatorship\n- Woman with creatinine clearance <75 ml/mn/1,73m²\n- Woman with liver insufficiency (Child Pugh grade C), AST, ALT 5 x ULN, bilirubin 2 x ULN.\n- Woman with known allergy to Letermovir\n- Contraindication for the administration of Letermovir listed in the SmPC of Prevymis®\n- Woman treated by pimozide, ergot alkaloids, dabigatran, atorvastatin, simvastatin, rosuvastatin, pitavastatine or cyclosporine.\n- Concomitant administration of millepertuis\n- Woman with hereditary intolerance to galactose, with lactose lapp deficiency, glucose or galactose malabsorption syndrome\n- Step2:\n- Participation to another interventional drug trial (category 1)\n- Subject protected by law under guardianship or curatorship\n- Maternal CMV infection after 15 weeks\n- creatinine clearance <75 ml/mn/1,73m²\n- liver insufficiency (Child Pugh grade C), AST, ALT 5 x ULN, bilirubin 2 x ULN.\n- Woman with known allergy to Letermovir or Valaciclovir\n- Contraindication for the administration of Letermovir and valaciclovirlisted in the SmPC of Prevymis® and Zelitrex®\n- Women with hypersensitivity to aciclovir\n- Concomitant administration of millepertuis\n- woman treated by pimozidee, ergot alkaloids, dabigatran, atorvastatin, simvastatin, rosuvastatin, pitavastatine or cyclosporine.\n- Woman with hereditary intolerance to galactose, with lactose lapp deficiency, glucose or galactose malabsorption syndrome"}

Primary endpoints

• {"endpoint_text":"- Primary endpoint: Negative CMV PCR (<500 IU/ml) in neonatal blood collected in the first day of life or in cord blood at termination of pregnancy","definition_or_measurement_approach":"Negative CMV PCR defined as <500 IU/ml measured in neonatal blood collected on the first day of life or in cord blood at termination of pregnancy (PCR assay threshold <500 IU/ml)."}

Secondary endpoints

• {"endpoint_text":"- Secondary objectives: (step 2) The following are to be compared between the 2 arms: -Proportion of asymptomatic neonates\n- Overall growth\n- Proportion of long-term sequelae at 2 years\n- Tolerance of treatment for mothers, fetuses and neonates\n- Adherence to treatment\n- Evolution of ultrasound features between Day0 and Week 2, Week 4, and Week 6 of treatment\n- Changes in cerebral and placental features between Day 1st magnetic resonance imaging (MRI) within the first month of inclusion and 2nd MR","definition_or_measurement_approach":"Comparative assessments between study arms using clinical evaluation for symptomatic status, growth measurements, longitudinal follow-up for sequelae at 2 years, safety/tolerability assessments for mothers/fetuses/neonates, treatment adherence measures, serial ultrasound assessments at Day 0, Week 2, Week 4, Week 6, and MRI comparison between the first-month MRI and the second MRI as specified."}

Other endpoints

• {"endpoint_text":"- Post-mortem examination in cases with medical termination of pregnancy (TOP)\n- CMV DNA levels in amniotic fluid and fetal blood (if done) at diagnosis (inclusion); amniotic fluid and saliva at birth; blood at day 3; saliva at day 3 and at M1 with the doctor discretion; urine retrieved in the first 3 days of life; saliva sampled at M6 (+/-2), M12 (+/-3), M18 (+/-3) and M24 (+/-3)\n- Anti-viral Letermovir transfer from mother to fetus\n- Search for mutation(s) in CMV genes associated with Letermovir resistance (UL56 and UL89)","definition_or_measurement_approach":"Laboratory measurements: quantitative CMV PCR on specified sample types and timepoints as listed; measurement of letermovir concentrations in maternal and fetal compartments to assess transfer; post-mortem examinations where applicable; genetic sequencing of CMV UL56 and UL89 to search for resistance-associated mutations."}

France

Earliest CTIS Part Ii Submission Date

19-06-2024

Latest Decision Or Authorization Date

13-04-2026

Processing Time Days

663

Number Of Sites

2

Number Of Participants

46

Primary sponsor

Full Name

Assistance Publique Hopitaux De Paris

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France