Efficacy Evaluation of 2LHERP® in Reducing Recurrent Orofacial Herpes Episodes: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial

The primary objective of this randomized, placebo-controlled, double-blind study is the evaluation of the efficacy of **2LHERP®** in reducing the number of recurrent orofacial herpes episodes over a 12-month period. This is clinically relevant as recurrent orofacial herpes infections can significantly impact patient quality of life and may require frequent medical interventions. By assessing the reduction in episode frequency, the study aims to determine the potential of 2LHERP® as a therapeutic option for patients experiencing frequent recurrences.

Secondary objectives include the comparison of the efficacy of 2LHERP® versus placebo based on several parameters:

• Number of episodes at 6 months
• Time to first episode during treatment
• Duration of episodes
• Symptomatology during the entire relapse period
• Use of rescue medication
• Evaluation of impact on quality of life
• Safety issues

The clinical trial involves **participants** aged between 16 and 80 years, comprising both male and female subjects. The study population includes individuals who have experienced recurrent orofacial herpes infections, specifically those with six or more episodes within the 12 months prior to study entry. Participants were selected based on their ability to understand and adhere to the study requirements, and women of childbearing age are required to use effective contraception. The trial does not include a vulnerable population. The sponsor has not provided information regarding the total number of participants. Participants are expected to maintain a stable sexual relationship throughout the study duration. The study aims to evaluate the efficacy of 2LHERP® in reducing the number of recurrent orofacial herpes episodes over a 12-month period.

The clinical trial is designed as a **randomized, placebo-controlled, double-blind** study to evaluate the efficacy of 2LHERP in patients with recurrent orofacial herpes infections. The primary objective is to assess the reduction in the number of recurrent episodes over a 12-month period. The trial will involve participants aged 16 to 80 years who have experienced six or more episodes of orofacial herpes infections in the 12 months preceding study entry. The study will span approximately seven years, with an estimated recruitment start date of March 10, 2020, and an estimated end date of March 31, 2027.

Participants will be randomly assigned to receive either the investigational product, 2LHERP, or a placebo. The investigational product is administered via **oromucosal use** in the form of granules in capsules to be opened. The maximum treatment period is six months, with a maximum daily dose of 380 mg and a total dose of 68.4 g. The study will include several key visits: an initial screening visit to confirm eligibility, regular follow-up visits to monitor progress and collect data, and an end-of-study visit to assess the final outcomes.

The expected length of participant involvement is 12 months, during which the primary endpoint will be the change from baseline in the number of herpes episodes. Secondary endpoints include remaining recurrence-free at six and 12 months, the number of episodes at six months, time to first recurrence, mean duration of episodes, level of pain, use of rescue medication, quality of life, and the occurrence of adverse events (AEs) and serious adverse events (SAEs). Conditions that may lead to early termination from the study include non-compliance with study procedures, withdrawal of consent, or the occurrence of significant adverse events that warrant discontinuation of the investigational product.

The clinical trial involves the administration of **2LHERP granules en gélules à ouvrir**, an experimental medication developed by Labo'Life Belgium. This pharmaceutical product is presented in the form of granules within capsules that are designed to be opened. The active substances in 2LHERP include **deoxyribonucleic acid (DNA)**, **ribonucleic acid (RNA)**, and specific nucleic acids targeting herpes simplex virus types I and II, as well as human leukocyte antigens types I and II. The maximum daily dose of 2LHERP is 380 mg, with a total maximum dose of 68.4 g over the treatment period. The medication is administered via the oromucosal route, and the treatment duration is capped at six months. Participant compliance with the dosing schedule is monitored throughout the study.

The study also includes a **placebo** as a comparator treatment. The placebo is utilized to maintain the double-blind nature of the trial, ensuring that neither the participants nor the investigators are aware of the treatment assignments. The placebo does not contain any active substances and is used to evaluate the efficacy of 2LHERP by providing a baseline for comparison. The administration route and frequency for the placebo are designed to match those of the experimental medication to ensure consistency in the study protocol.

The efficacy of the investigational product, 2LHERP, in the treatment of recurrent orofacial herpes infections will be assessed through a randomized, placebo-controlled, double-blind clinical trial. The primary endpoint for evaluating efficacy is the change from baseline in the number of episodes of herpes infections observed over a 12-month period. The baseline value is defined as the number of episodes experienced in the 12 months preceding study enrollment.

Secondary endpoints include several parameters: the proportion of patients remaining herpes infection recurrence-free at 6 and 12 months post-treatment initiation, the number of herpes infection episodes observed at 6 months, the time to first recurrence during treatment, the mean duration of episodes, the level of pain during episodes, the use of rescue medication, quality of life assessments, and the occurrence of adverse events (AEs) and serious adverse events (SAEs). These endpoints will be measured and collected at specified intervals throughout the study duration to ensure comprehensive data analysis.