Evaluation of Low-Dose Atropine Sulfate Eye Drops for Myopia Progression Control in Pediatric Caucasian Patients: A Randomized, Placebo-Controlled Trial

The primary objective of this study is to demonstrate the **superiority** of low-dose atropine 0.02% eye drops compared to placebo in controlling **progressive myopia** in children of Caucasian origin. This is measured by the change in cycloplegic refraction per year, expressed in diopters per year (D/year), after one year of treatment. This objective is clinically relevant as it addresses the need for effective interventions in managing myopia progression, which can lead to significant visual impairment and increased risk of ocular complications.

Secondary objectives include:

• Comparing atropine 0.02% and placebo with respect to the increase in axial eye length per year (mm/year).
• Assessing visual acuity at both distance and near.
• Evaluating changes in pupil size.
• Investigating accommodation capabilities.
• Ensuring safety regarding ocular and systemic side effects.

The clinical trial focuses on children of **Caucasian** origin diagnosed with **progressive myopia**. The study population includes both male and female participants aged 8 to 12 years, up to the day before their 13th birthday. Participants are required to have myopia ranging from -1 D to -6 D, with a documented or reported annual progression of at least 0.5 D. The trial involves a vulnerable population, as it includes children. The sponsor has not provided information regarding the total number of participants. Selection criteria necessitate that participants and their guardians provide written informed consent, and that participants have the ability to understand and comply with trial procedures. Lifestyle considerations such as diet, physical activity, or habits are not specified in the available data.

The clinical trial is designed to evaluate the efficacy of **low-dose atropine sulfate** eye drops in controlling **progressive myopia** in children. This is a Phase III, randomized, double-blind, placebo-controlled study. The trial will involve the administration of atropine sulfate 0.02% and 0.01% eye drops, as well as a placebo, all formulated as eye drops for **ophthalmic use**. The primary objective is to demonstrate the superiority of atropine sulfate 0.02% over placebo in reducing the progression of myopia, measured as the change in cycloplegic refraction per year after one year of treatment. Secondary endpoints include the change in axial eye length per year and the categorized rate of change in refraction and eye length after one year.

The trial is expected to last until October 31, 2027, with recruitment having commenced on October 19, 2021. Participants will be involved in the study for a maximum treatment period of 24 months. The study will include several key visits: an initial screening visit to confirm eligibility, regular follow-up visits to monitor progress and adherence to the treatment regimen, and an end-of-study visit to assess the final outcomes. Inclusion criteria require participants to be male or female children aged 8 to 12 years with myopia ranging from -1 D to -6 D and a documented annual progression of at least 0.5 D. Written informed consent must be obtained from the participants and their legal guardians.

Participants may be withdrawn from the study if they fail to comply with the trial procedures, experience adverse effects that necessitate discontinuation, or if they or their guardians choose to withdraw consent. The study is conducted under strict adherence to international guidelines and local laws to ensure the safety and well-being of all participants. The trial's design and methodology are structured to provide robust data on the efficacy of low-dose atropine sulfate in managing progressive myopia in the pediatric population.

The clinical trial involves the use of **Atropine Sulfate 0.02% eye drops, solution** as the experimental medication. This pharmaceutical form is an eye drop solution intended for **ophthalmic use**. The active substance, **atropine sulfate**, is of chemical origin. The maximum daily dose is 0.02% weight/volume, with a total treatment period of up to 24 months. The administration route is strictly ophthalmic, and the medication is not formulated specifically for pediatric use. Participant compliance will be monitored through regular follow-ups and assessments to ensure adherence to the dosing schedule.

Another experimental treatment in the study is **Atropine Sulfate 0.01% eye drops, solution**. Similar to the 0.02% formulation, this medication is also an eye drop solution for ophthalmic use, containing the same active substance, atropine sulfate, of chemical origin. The maximum daily dose for this formulation is 0.01% weight/volume, with a treatment duration of up to 24 months. The administration and compliance monitoring procedures are consistent with those of the 0.02% formulation.

The study also includes a **placebo** treatment, which is an eye drop solution identical to the investigational medicinal product (IMP) except for the absence of the active substance. This placebo is administered via the ophthalmic route, with a maximum treatment period of 12 months. The placebo is used to assess the efficacy of the experimental treatments by providing a baseline for comparison. Compliance with the placebo administration will be monitored in the same manner as the active treatments.

Efficacy in the clinical trial titled "Low-dose AtropIne for Myopia control in children" will be assessed using specific primary and secondary endpoints. The primary endpoint is the change in **cycloplegic refraction** per year, measured in diopters per year (D/year), after one year of treatment. This endpoint aims to demonstrate the superiority of low-dose atropine 0.02% eye drops compared to placebo in controlling myopia progression in children of Caucasian origin.

Secondary endpoints include the change in axial eye length per year, measured in millimeters per year (mm/year), and the categorized rate of change in refraction and eye length after one year. These measurements will provide additional insights into the efficacy of the treatment in altering the physical parameters associated with myopia progression.