Dose-Finding Study of Atropine Sulfate Eye Drops for Inhibition of Myopia Progression in European Pediatric Population

The primary objective of this study is to evaluate the optimal dose of low-dose **atropine** eye drops compared to placebo for the inhibition of **myopia** progression in children. This is clinically relevant as myopia is a common refractive error in children that can lead to significant visual impairment if not effectively managed. Identifying the optimal dose of atropine could provide a valuable therapeutic option for slowing the progression of myopia, potentially reducing the risk of associated complications and improving long-term visual outcomes.

Secondary objectives include evaluating the anatomical and functional effects of low-dose atropine eye drops compared to placebo. This assessment is crucial for understanding the broader impact of atropine treatment on ocular health and function, beyond its role in inhibiting myopia progression.

The clinical trial focuses on evaluating the optimal dose of low-dose atropine eye drops for inhibiting **myopia progression in children**. The study population comprises both male and female subjects aged 6 to 12 years. Participants are required to have myopia between -1.0 and -4.0 diopters, with documented progression within the past 12 months in at least one eye. The trial includes children who are considered a vulnerable population, and both genders are represented. The selection criteria ensure that female participants of childbearing potential adhere to highly effective contraceptive methods. The sponsor has not provided information regarding the total number of participants. Parents or legal guardians must provide informed consent for their children's participation. The trial does not specify any particular lifestyle considerations such as diet or physical activity.

The clinical trial is designed as a **randomized, double-blind, placebo-controlled** study to evaluate the optimal dose of low-dose **atropine sulfate** eye drops for inhibiting myopia progression in children. The trial will involve multiple doses of atropine sulfate (0.05%, 0.025%, 0.01%, and 0.005%) compared to a placebo, with all formulations administered as eye drops in a single-dose container. The study is set to span approximately 379 days, with participant involvement expected to last for the entire duration unless early termination criteria are met. Such criteria may include adverse reactions or non-compliance with the study protocol.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to assess eligibility based on criteria such as age (6 to 12 years), myopia range, and progression history. Following successful screening, participants will be randomized to receive one of the atropine doses or placebo. The primary endpoint is the change in myopia, measured by spherical equivalent via autorefractor with cycloplegia over 12 months. Secondary endpoints include changes in axial eye growth, anterior chamber depth, and other ocular parameters, as well as safety assessments such as intraocular pressure and incidence of adverse events.

Follow-up visits will be scheduled periodically to monitor efficacy and safety, with assessments including visual acuity tests and pupil size measurements under various lighting conditions. The end-of-study visit will conclude the trial, where final evaluations will be conducted to gather comprehensive data on the treatment's impact. The trial's estimated recruitment start date was August 1, 2022, with an anticipated end date of June 3, 2025. Participants' involvement is contingent upon adherence to the study protocol, and any deviation may result in withdrawal from the trial.

The clinical trial involves the administration of several formulations of **atropine sulfate** eye drops, each provided in a single-dose container. The experimental medications include Atropine Sulfate 0.025% Eye Drops, Atropine Sulfate 0.005% Eye Drops, Atropine Sulfate 0.01% Eye Drops, and Atropine Sulfate 0.05% Eye Drops. Each formulation is presented as an eye drop solution, intended for **topical** administration. The dosage for each formulation is one drop per day, with a maximum treatment period of 379 days. The active substance, atropine sulfate, is of chemical origin, and the pharmaceutical form is consistent across all experimental treatments. Participant compliance with the dosing schedule will be monitored throughout the study.

In addition to the experimental treatments, a **placebo** eye drop solution is utilized as a comparator in this double-blind, placebo-controlled study. The placebo is also provided in a single-dose container and is administered topically as one drop per day, mirroring the administration schedule of the experimental treatments. The placebo is designed to be indistinguishable from the active formulations in appearance and administration method, ensuring the integrity of the blinding process. The placebo contains no active pharmaceutical ingredient and is classified as a structurally diverse substance.

The efficacy of the clinical trial will be assessed through both primary and secondary endpoints. The primary efficacy endpoint is the change in **myopia** as determined by the spherical equivalent, measured using an autorefractor with cycloplegia over a 12-month period following the initiation of low-dose atropine treatment. This measurement will provide a quantitative assessment of the progression of myopia in the study participants.

Secondary efficacy endpoints include a range of ocular parameters: changes in axial eye growth, anterior chamber depth, IOL-power for Spheris 209, lens thickness, pupil size under photopic and scotopic conditions, accommodation, and visual acuity metrics such as best corrected visual acuity and distance corrected near visual acuity. Additionally, the effects of atropine as a function of iris pigmentation will be evaluated over the same 12-month treatment period. These endpoints will be measured using appropriate ophthalmic instruments and validated scales to ensure accuracy and reliability of the data collected.