A Randomized, Open-Label, Placebo-Controlled Trial Evaluating Aciclovir Gel Versus Aciclovir Cream in Recurrent Herpes Labialis Patients

The primary objective of this clinical trial is to evaluate the **efficacy** of Lipovir® Gel (Acyclovir 5%) compared to Zovirax® Cream (Acyclovir 5%) in patients with **recurrent herpes labialis** (RHL). This is clinically relevant as it aims to determine whether Lipovir® Gel is as effective as the established treatment, Zovirax® Cream, in managing RHL, which is a common and recurrent viral infection.

Secondary objectives include:

• Evaluating the local **tolerability** and acceptability of Lipovir® Gel compared to Zovirax® Cream in patients with RHL.
• Assessing the **safety** of Lipovir® Gel compared to Zovirax® Cream in the same patient population.

The clinical trial involves participants diagnosed with **recurrent herpes labialis** (RHL), aiming to assess the efficacy of Lipovir® Gel compared to Zovirax® Cream. The study population includes both male and female subjects aged 18 years and older. Participants are required to have experienced at least three recurrences of herpes labialis within the past year, with at least half of these episodes being preceded by recognizable prodromal symptoms such as itching, redness, burning, tingling, or a sense of irritation, and followed by classical lesions like ulcers, vesicles, or hard crusts. The trial does not involve a vulnerable population. The sponsor has not provided information regarding the total number of participants. Participants must be capable of reading, understanding, and signing the informed consent document, as well as adhering to study procedures, including maintaining a study diary. Lifestyle factors such as diet, physical activity, or habits are not specified as part of the selection criteria.

The clinical trial is designed to evaluate the **efficacy** and tolerability of Lipovir Gel (Acyclovir 5%) compared to Zovirax Cream (Acyclovir 5%) and a placebo in patients with recurrent herpes labialis. This is a multicenter, randomized, open-label trial with blind evaluation, and it is controlled for both active and placebo groups. The trial follows a non-inferiority design to ensure that the new treatment is not worse than the existing standard treatment. The estimated duration of the trial is from June 2024 to October 2025, with participant recruitment starting in June 2024.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as having at least three recurrences of herpes labialis in the past year and being 18 years or older. Following the screening, eligible participants will be randomized into one of the treatment groups. The trial includes follow-up visits to monitor the duration of episodes, local product tolerability, product acceptability, and the incidence of adverse events. The primary endpoint is the duration of the episode, assessed by the investigator through clinical observation and participant diaries. Secondary endpoints include self-reported tolerability and acceptability of the product, as well as the incidence of adverse events.

The expected length of participant involvement is up to 10 days, corresponding to the maximum treatment period. Conditions that may lead to early termination from the study include non-compliance with study procedures or the occurrence of significant adverse events. The trial aims to provide comprehensive data on the comparative efficacy and safety of the treatments, contributing valuable insights into the management of recurrent herpes labialis.

The clinical trial involves the evaluation of **Lipovir 50 mg/g Gel**, an experimental medication containing the active substance **aciclovir**. This pharmaceutical form is a gel, intended for **cutaneous use**. The dosage is 50 mg of aciclovir per gram of gel, with a maximum daily dose of 20 grams and a total maximum dose of 2 grams. The treatment period is limited to a maximum of 10 days. The gel is manufactured by Laboratorios Ojer Pharma, S.L., and is classified under the ATC code D06BB03, indicating its use as an antiviral agent. Participant compliance with the dosing schedule will be monitored throughout the trial.

The comparator treatment in this study is **Zovirax 50 mg/g Cream**, which also contains **aciclovir** as the active ingredient. This cream is similarly intended for **cutaneous use** and is administered at a dosage of 50 mg of aciclovir per gram of cream. The maximum daily and total doses are consistent with those of the experimental gel, at 20 grams and 2 grams, respectively, over a treatment period of up to 10 days. Zovirax Cream is produced by Haleon Spain, S.A., and shares the same ATC classification as Lipovir Gel, serving as an antiviral treatment.

A **placebo** is also utilized in this trial to serve as a control. The placebo does not contain any active substance and is used to assess the efficacy and tolerability of the active treatments by providing a baseline for comparison. The placebo is administered in a manner consistent with the active treatments, although specific details regarding its pharmaceutical form and administration route are not applicable.

The efficacy of the investigational products in the clinical trial will be assessed using the **Duration of Episode (DOE)** as the primary endpoint. This parameter will be evaluated by the investigator through clinical observation and review of the participant's diary. For vesicular lesions, DOE is defined as the time from treatment initiation to healing, marked by the loss of crust, although residual erythema may still be present. For non-vesicular lesions, DOE is the time from treatment initiation to the return to normal skin or cessation of symptoms, whichever occurs last.

Secondary endpoints include local product tolerability, which will be self-reported by the participant, product acceptability as assessed by the participant, and the incidence of adverse events. These secondary endpoints will provide additional insights into the overall efficacy and safety profile of the treatments under investigation. The trial is designed to compare the efficacy and tolerability of Lipovir® Gel (Acyclovir 5%) with Zovirax® Cream (Acyclovir 5%) in patients with Recurrent Herpes Labialis.