Congenital CMV treated with valaciclovir during pregnancy: a prospective cohort study

The primary objective of this study is to evaluate the **effectivity** of valaciclovir in preventing vertical transmission of **cytomegalovirus (CMV)** during pregnancy, specifically in cases of first trimester primary maternal CMV infections. This is clinically relevant as congenital CMV infection can lead to significant neonatal morbidity and long-term developmental issues. By assessing the efficacy of valaciclovir, the study aims to provide insights into potential preventive strategies for reducing the incidence of congenital CMV.

Secondary objectives include: - Assessing the long-term safety of valaciclovir treatment during pregnancy for both the mother and the fetus. - Increasing patient awareness of CMV during pregnancy. - Standardizing first trimester CMV screening for pregnant women. - Recalculating the cost-effectiveness of population screening for CMV during pregnancy in Flanders.

The clinical trial focuses on a study population consisting exclusively of **female** participants, aged 18 years or older, who have a proven first trimester primary **cytomegalovirus (CMV)** infection. The trial aims to assess the effectiveness of valaciclovir in preventing vertical CMV transmission during pregnancy. The participants are selected based on their voluntary written informed consent, either personally or through a legally authorized representative. The study does not include male participants and involves a vulnerable population, given the nature of the condition and the demographic involved. The sponsor has not provided information regarding the total number of participants. Lifestyle considerations such as diet, physical activity, or habits are not specified in the available data.

The clinical trial is designed to evaluate the **effectivity** of **valaciclovir** in preventing vertical transmission of **congenital CMV infection** during pregnancy, specifically in cases of first trimester primary maternal CMV infections. This is a Phase 3, prospective cohort study, which is not categorized as low intervention. The trial will employ a controlled design, with participants receiving **valaciclovir** in the form of 500 mg film-coated tablets administered orally. The maximum daily dose is set at 8 grams, with a total treatment period not exceeding 11 days. The trial is expected to conclude by July 2031, with recruitment having commenced in August 2023.

Participants will undergo a series of study visits, beginning with an inclusion visit where eligibility is confirmed through criteria such as age (18 years or older) and proven first trimester primary CMV infection. Informed consent must be obtained prior to any screening procedures. Follow-up visits will include assessments at 20 weeks gestation, where the primary endpoint of vertical transmission rate will be evaluated via CMV PCR on amniotic fluid. This will be reconfirmed postnatally with a urine sample PCR. Secondary endpoints include imaging assessments for transmission indicators, maternal and fetal safety evaluations, and long-term effects such as hearing and neurodevelopmental follow-ups.

The expected duration of participant involvement extends from the first trimester of pregnancy through to postnatal assessments, with long-term follow-up continuing until the child reaches five years of age. Conditions that may lead to early termination from the study include withdrawal of consent or any adverse events that compromise participant safety. The study is structured to ensure rigorous monitoring and data collection throughout the trial period, adhering to ethical standards and regulatory requirements.

The clinical trial involves the administration of **Valaciclovir**, marketed under the name Valaciclovir Sandoz 500 mg filmomhulde tabletten. This experimental medication is presented in the form of a **film-coated tablet**. The active substance, **valaciclovir**, is of chemical origin. The medication is administered orally. The maximum daily dose is 8 grams, with a total maximum dose of 90 grams over the course of the treatment. The treatment period is limited to a maximum of 11 days. The pharmaceutical product is not a pediatric formulation and is not classified as an orphan drug. The trial aims to assess the effectiveness of valaciclovir in preventing vertical transmission of congenital cytomegalovirus (CMV) during pregnancy, specifically in cases of first trimester primary maternal CMV infections.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are utilized. The focus is solely on the administration of the experimental medication, Valaciclovir Sandoz. Participant compliance with the dosing schedule is monitored to ensure adherence to the prescribed regimen. The trial does not involve any additional medicinal products or devices. The study is conducted under the authorization of SANDOZ N.V., with the product holding a marketing authorization number BE341327 in Belgium.

Efficacy in this clinical trial will be assessed by evaluating the primary and secondary endpoints related to the prevention of vertical **Cytomegalovirus (CMV)** transmission during pregnancy. The primary endpoint is the rate of vertical transmission, which will be assessed using CMV PCR on amniotic fluid collected during an amniocentesis at 20 weeks of gestation. This result will be reconfirmed by PCR on a urine sample postnatally. Secondary endpoints include imaging abnormalities indicative of vertical transmission, assessed via ultrasound every two weeks and MRI at 30 weeks of gestational age. Maternal safety will be evaluated through blood analysis, including hematology, liver function, and kidney function, as well as clinical assessments. Fetal safety will be assessed prenatally by ultrasound, at birth through blood analysis on umbilical cord blood, postnatal urine samples, and MRI postnatally. Long-term effects will be monitored through hearing assessments conducted yearly until the child reaches four years of age and neurodevelopmental follow-up at 1, 2, and 5 years of age.