Phase 3 Randomized Double-Blind Study of Sodium Sulfide Nonahydrate and Saccharomyces Cerevisiae Type D Extract in Acute Rhinitis, Rhinopharyngitis, and Rhinosinusitis

The primary objective of this study is to evaluate the **efficacy** of Actisoufre nasal spray, administered in a pressurized container, compared to placebo in adult and pediatric subjects over 6 years of age with acute rhinitis, rhinopharyngitis, and rhinosinusitis not requiring antibiotic therapy. This evaluation is clinically relevant as it aims to determine the therapeutic potential of Actisoufre in managing symptoms of these common upper respiratory conditions, potentially offering a non-antibiotic treatment option.

Secondary objectives include:

• Evaluating Actisoufre's effect on sleep, which is important for understanding its impact on overall patient well-being.
• Assessing the patient's subjective impression of Actisoufre's efficacy in resolving symptoms of acute rhinitis, rhinopharyngitis, and rhinosinusitis, providing insight into patient satisfaction and perceived benefit.
• Evaluating Actisoufre's effect on quality of life, which is crucial for determining the broader implications of treatment on daily functioning and health-related quality of life.
• Evaluating the safety of Actisoufre, ensuring that the treatment is not only effective but also safe for use in the specified population.

The clinical trial involves a study population comprising both **male** and **female** subjects, including children aged 6-18 years and adults aged 18-70 years. The participants are individuals diagnosed with acute rhinitis, rhinopharyngitis, or rhinosinusitis, conditions that do not require antibiotic therapy. The trial population was selected based on their clinical diagnosis and the sudden onset of at least two relevant symptoms, such as nasal blockage, obstruction, congestion, or rhinorrhea, occurring within 48 hours prior to enrollment. Participants are required to have the cognitive and functional abilities to answer symptom-specific questions and must be willing to comply with study procedures. Additionally, they must agree to use acceptable birth control methods during the study. The sponsor has not provided information regarding the total number of participants. The study includes a vulnerable population, and both genders are represented. Lifestyle considerations such as diet and physical activity are not specified in the available data.

The clinical trial is designed as a **randomized**, **double-blind**, controlled, two-arm, parallel-group, multicenter, phase 3 study. It aims to evaluate the efficacy of Actisoufre nasal spray compared to a placebo in treating **acute rhinitis**, **rhinopharyngitis**, and **rhinosinusitis** in individuals over 6 years old who do not require antibiotic therapy. The trial will involve both adult and pediatric populations, with the treatment administered three times daily for a duration of 7 days. The study is expected to commence recruitment on September 17, 2025, and conclude by March 31, 2026.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on specific criteria, such as age, sex, and clinical diagnosis. The primary inclusion criteria require participants to have a sudden onset of at least two relevant symptoms, such as nasal blockage or rhinorrhea, for no more than 48 hours prior to enrollment. Participants must also be willing to comply with study procedures and use acceptable birth control methods if applicable. The primary exclusion criteria are not specified in the provided data.

Following the screening, participants will be randomly assigned to receive either the Actisoufre nasal spray or a placebo. The primary endpoint will assess changes in nasal symptoms using the Common Cold Symptoms Severity Questionnaire (CCSS) at various time points, including baseline (Day 1), Day 2, Day 3, Day 4, and Day 8. Secondary endpoints will evaluate changes in sleep quality, quality of life, onset of immediate relief, use of nasal decongestants, concomitant medication use, and the occurrence of adverse events.

The expected length of participant involvement is approximately 8 days, with study visits scheduled at baseline, Day 4, and Day 8. Conditions that may lead to early termination from the study include non-compliance with study procedures or the occurrence of serious adverse events. The trial's design ensures that neither the participants nor the investigators will know which treatment is being administered, maintaining the integrity of the double-blind methodology.

The clinical trial involves the evaluation of **Actisoufre**, a nasal/oromucosal spray solution, which is administered in a pressurized container. The active substances in this experimental medication are **sodium sulfide nonahydrate** and **Saccharomyces cerevisiae type D extract**. The pharmaceutical form of Actisoufre is a nasal/oromucosal spray, and it is applied as a nasal spray. The dosage regimen involves administering the spray three times daily into each nostril over a period of 7 days. The maximum daily dose is 6.6 ml, with a total maximum dose of 46.2 ml over the treatment period. The product is manufactured by Laboratoires Grimberg and has undergone blinding, which includes a change in labeling to maintain the integrity of the study.

The study also includes a placebo comparator, referred to as Actisoufre Placebo. This placebo is used to assess the efficacy of the experimental treatment by providing a control for comparison. The placebo does not contain any active substances and is designed to mimic the appearance and administration route of the experimental medication. The placebo is administered following the same schedule as the experimental treatment, ensuring consistency in the trial protocol. The use of a placebo is critical in maintaining the double-blind nature of the study, where neither the participants nor the investigators are aware of the treatment assignments.

The efficacy of Actisoufre nasal spray will be assessed in a phase 3, randomized, double-blind, placebo-controlled clinical trial involving adult and pediatric participants over 6 years old with acute rhinitis, rhinopharyngitis, and rhinosinusitis not requiring antibiotic therapy. The primary endpoint for evaluating efficacy is the change in nasal symptoms, including nasal obstruction, rhinorrhea, thick mucus, sneezing, and cough. These symptoms will be assessed using the "Common Cold Symptoms Severity Questionnaire" (CCSS) at multiple time points: Baseline (Day 1), Day 2, Day 3, Day 4, and Day 8.

Secondary endpoints include changes in the quality of sleep and patient's Quality of Life, assessed using the Visual Analog Scale (VAS) at Baseline (Day 1), Day 4, and Day 8. The onset of immediate relief will be evaluated after the product application is completed at Day 1 and once daily up to Day 4. The need for nasal decongestants as emergency treatment will be recorded on Day 8, and the use of concomitant medications will be assessed from Baseline to the end of the study. Additionally, the number of Adverse Events and Serious Adverse Events will be compared between the intervention and control groups at Baseline, Day 4, and Day 8.