Evaluation of Safety and Efficacy of Fluocinolone Acetonide Intravitreal Implant in Pediatric Patients with Recurrent Non-Infectious Uveitis of the Posterior Segment

The primary objective of this study is to evaluate the **safety** and **efficacy** of ILUVIEN® 190 micrograms intravitreal implant in pediatric subjects aged 6 to less than 18 years with recurrent non-infectious uveitis affecting the posterior segment of the eye. This is clinically relevant as non-infectious uveitis can lead to significant visual impairment and the management of this condition in a pediatric population is crucial for preventing long-term ocular complications.

Secondary objectives include:

• Assessing the incidence of recurrence of non-infectious uveitis affecting the posterior segment in the study eye.
• Evaluating the incidence and onset of secondary lens opacity and extraction.
• Assessing the incidence of secondary intraocular pressure (IOP) elevation.

The clinical trial involves a total of **15 participants** diagnosed with **non-infectious uveitis** affecting the posterior segment of the eye. The study population comprises both male and female subjects aged between 6 and 18 years. Participants were selected based on specific criteria, including a history of recurrent non-infectious uveitis in the study eye, not adequately controlled by standard care due to adverse effects or poor response. The trial population includes individuals who have been treated with systemic corticosteroids or other systemic therapies for at least three months within the previous year. Participants are required to have a visual acuity of at least 35 letters on the ETDRS chart in the study eye and no evidence of medically unstable systemic disease. The study does not include individuals planning elective ocular surgery during the trial or those expecting to relocate outside the clinical center's coverage area within the next 36 months. The trial is designed to evaluate the safety and efficacy of ILUVIEN® 190μg in pediatric subjects, with an emphasis on compliance with treatment and follow-up procedures.

The clinical trial is a **non-randomised**, open-label, uncontrolled, multi-centre, phase IIIb study designed to evaluate the safety and efficacy of **fluocinolone acetonide** 190 micrograms intravitreal implant in pediatric subjects aged 6 to less than 18 years with recurrent non-infectious uveitis affecting the posterior segment of the eye. The trial is expected to commence recruitment on December 1, 2023, and conclude by December 1, 2027, with an overall duration of 36 months for each participant. The study involves a series of visits, beginning with an inclusion (screening) visit to assess eligibility based on criteria such as age, medical history, and current health status. Participants must not plan to undergo elective ocular surgery during the trial and must have a history of recurrent uveitis not adequately controlled by standard care.

Following the screening, eligible participants will receive the intravitreal implant and undergo regular follow-up visits to monitor treatment outcomes and safety. These visits will assess primary endpoints, including the absence of cystoid macular oedema and a decrease in vitreous haze grade, as well as secondary endpoints such as changes in visual acuity and the incidence of ocular adverse events. The end-of-study visit will evaluate the long-term effects of the treatment and document any recurrence of uveitis. Participants are expected to remain in the study for the full duration unless conditions such as significant adverse events or non-compliance with the protocol necessitate early termination. The trial aims to provide comprehensive data on the implant's efficacy and safety profile in the pediatric population with this specific ocular condition.

The clinical trial involves the use of **ILUVIEN**, a 190 micrograms **intravitreal implant** in an applicator, as the experimental medication. The active substance in ILUVIEN is **fluocinolone acetonide**, a corticosteroid of chemical origin. The pharmaceutical form of the product is an implant, specifically designed for **intravitreal use**. The implant is administered directly into the vitreous cavity of the eye. The maximum total dose of the implant is 190 micrograms, with a maximum daily dose of 0.2 micrograms. The treatment period for the implant is up to 36 months. The outer packaging of the investigational medicinal product (IMP) will be labeled "for clinical trial use only" to ensure compliance with trial protocols.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are utilized. The trial is designed as a non-randomised, open-label, uncontrolled, multi-centre, phase IIIb study. The primary objective is to evaluate the safety and efficacy of ILUVIEN in paediatric subjects aged 6 to less than 18 years with recurrent non-infectious **uveitis** affecting the posterior segment of the eye. Participant compliance with the dosing schedule will be monitored throughout the study to ensure adherence to the treatment protocol.

The efficacy of the **fluocinolone acetonide** 190 micrograms intravitreal implant will be assessed in a phase IIIb clinical trial involving pediatric subjects with recurrent non-infectious uveitis affecting the posterior segment of the eye. The primary endpoints for evaluating efficacy include the absence of cystoid macular oedema as determined by Optical Coherence Tomography, a decrease from baseline in vitreous haze grade by at least two steps or the absence of vitreous haze, the rate of cataract formation, and the rate of intraocular pressure (IOP) elevation. IOP changes will be monitored for significant increases, including thresholds of IOP >21 mmHg, >25 mmHg, >30 mmHg, and increases from baseline of 10 mmHg or more.

Secondary endpoints will further assess efficacy by evaluating the absence of cystoid macular oedema and changes in vitreous haze at study completion, the recurrence rate of uveitis post-treatment compared to the 12 months prior to enrollment, and the time to recurrence of non-infectious uveitis in the study eye. Additional secondary measures include changes in macular oedema, Best Corrected Visual Acuity, vitreous haze, anterior chamber cell grade, and the incidence of secondary increases in IOP, including those requiring surgical intervention. The study will also monitor the incidence and onset of secondary lens opacity and extraction, the number of adjunctive treatments required for uveitis recurrences, the presence of active chorioretinal and retinal vascular lesions, the incidence of ocular infection, changes in the cup-to-disc ratio, and the incidence of ocular and non-ocular adverse events.