Efficacy and Safety of Valaciclovir in Dose-Dependent Prevention and Treatment of Primary Cytomegalovirus Infection in Pregnant Women

The primary objective of this study is to compare the **efficacy** and **safety** of valacyclovir in the prevention of transmission and treatment of intrauterine infection in pregnant women with primary **cytomegalovirus (CMV) infection** in a dose-dependent manner. This is clinically relevant as it aims to determine the optimal dosing strategy for valacyclovir, potentially improving maternal and fetal outcomes by reducing the risk of CMV transmission and associated complications.

Secondary objectives include:

• Comparison of the efficacy of valacyclovir in the prevention of transmission and treatment of intrauterine infection in pregnant women with primary CMV infection according to the drug dose used.
• Safety evaluation of valacyclovir depending on the drug dose used.
• Evaluation of patients' adherence to therapeutic recommendations depending on the drug dose used.

The clinical trial focuses on **pregnant women** aged 18 years and older, specifically targeting those with a **primary cytomegalovirus (CMV) infection**. The study population is exclusively female, as the trial is concerned with the prevention and treatment of intrauterine infection. Participants are required to have seroconverted, indicated by the presence of IgG antibodies to CMV, which were previously negative in the current pregnancy. Additionally, antibodies to CMV in the IgM and IgG classes must exhibit low avidity, and these antibodies should be present before 16 weeks of pregnancy. The trial involves a vulnerable population, as it includes pregnant women, and requires confirmed singleton pregnancies. Participants must provide written informed consent to be included in the study. The sponsor has not provided information regarding the total number of participants or specific lifestyle considerations such as diet or physical activity.

The clinical trial is designed to evaluate the **efficacy** and safety of **valaciclovir** in the prevention and treatment of intrauterine infection in pregnant women with primary **cytomegalovirus (CMV) infection**. This is a Phase IV, randomized, double-blind, controlled trial with a non-inferiority design. The trial will span approximately 32 months, with an estimated recruitment start date of January 1, 2024, and an estimated end date of August 31, 2026. Participants will be randomly assigned to receive different doses of valaciclovir, administered orally in the form of film-coated tablets.

The study will include several key visits: an initial screening visit, multiple follow-up visits, and an end-of-study visit. During the screening visit, eligibility will be confirmed based on criteria such as age (18 years and older), seroconversion of CMV IgG antibodies, and confirmed singleton pregnancy. Participants will provide written informed consent. Follow-up visits will assess primary and secondary endpoints, including the percentage of newborns without detectable CMV DNA in amniotic fluid and the level of CMV DNA replication in fetal and maternal blood. The end-of-study visit will conclude the participant's involvement, which is expected to last up to 16 weeks, corresponding to the maximum treatment period.

Participants may be withdrawn from the study if they experience significant adverse events, fail to adhere to the study protocol, or withdraw consent. The primary endpoint will be evaluated at visits 4 and 5, while secondary endpoints will be assessed throughout the study. The trial aims to provide valuable insights into the dose-dependent effects of valaciclovir on CMV transmission and treatment efficacy, contributing to improved management strategies for pregnant women with primary CMV infection.

The clinical trial involves the administration of **valaciclovir**, marketed under the name VACICLOR 500 MG, in the form of **film-coated tablets**. Each tablet contains 500 mg of the active substance, valaciclovir, which is a chemical compound. The medication is administered orally. The maximum daily dose is 8 grams, with a total maximum dose of 896 grams over the course of the treatment. The treatment period is limited to a maximum of 16 weeks. The pharmaceutical product is manufactured by Actavis Group PTC EHF and is not a pediatric formulation. The trial aims to evaluate the efficacy and safety of valaciclovir in preventing the transmission and treatment of intrauterine infection in pregnant women with primary cytomegalovirus (CMV) infection, with a focus on dose dependency.

In addition to the experimental treatment, the study may involve the use of non-experimental treatments, such as standard-of-care therapies, which include nucleosides and nucleotides, excluding reverse transcriptase inhibitors. These treatments are not the primary focus of the study but may be used as comparator treatments or to ensure comprehensive care for participants. Compliance with the dosing schedule will be monitored throughout the trial to ensure adherence to the prescribed regimen and to assess the impact of the treatment on the study's objectives.

The clinical trial aims to assess the efficacy of **valaciclovir** in preventing the transmission and treatment of intrauterine infection in pregnant women with primary cytomegalovirus (CMV) infection. Efficacy will be evaluated using both primary and secondary endpoints. The primary endpoint is the percentage of newborns in whom CMV DNA is not detected in the amniotic fluid, assessed at visits 4 and 5. Secondary endpoints include the level of CMV DNA replication in fetal blood compared to maternal blood, platelet count in the fetus depending on the drug dose, the percentage of missed doses in the compared groups, and the percentage of newborns without detectable CMV DNA in the amniotic fluid depending on virus replication levels, all assessed at specified visits. Additionally, the frequency of adverse events in the study groups will be evaluated.