Efficacy of Intravitreal Bevacizumab as Initial and Adjuvant Therapy in Coats' Disease: A Multicenter Randomized Controlled Trial

The primary objective of this multicenter randomized controlled trial is to compare the **efficacy** of treatment with intravitreal (IVT) injection of anti-VEGF (bevacizumab, Avastin®) on the stage of **Coats' disease**, versus reference treatment with laser photocoagulation, 6 months after initiation of study treatment. This objective is clinically relevant as it aims to determine the potential benefits of bevacizumab in altering the progression of Coats' disease, which could lead to improved management strategies for this condition.

Secondary objectives include: - Comparing the efficacy of IVT injections of anti-VEGF as initial treatment and then adjuvant to laser photocoagulation sessions versus laser photocoagulation treatment alone, at 2 months, 4 months, and 9 months after initiation of study treatment. - Evaluating the safety of intravitreal injections of bevacizumab. - Measuring the agreement between two independent expert ophthalmologist assessors of the stage of Coats' disease at each assessment (at 0, 1, 2, 4, 6, and 9 months).

The clinical trial involves a study population diagnosed with **Coats' disease**, specifically targeting individuals aged 16 years or younger. Both male and female participants are included, and the trial acknowledges the involvement of a vulnerable population. The sponsor has not provided the total number of participants. Participants were selected based on specific criteria, including a confirmed diagnosis of Coats' disease through fundus examination and fluorescein angiography, and must be in stages 2 or 3 according to the Shields classification. Additionally, participants must be naïve to any ocular treatment on the affected eye and beneficiaries of a Social Security scheme. The trial requires the free, informed, written consent of both holders of parental authority. No specific lifestyle considerations such as diet or physical activity are mentioned in the trial data.

The clinical trial is designed as a **randomized**, controlled study to evaluate the efficacy of intravitreal anti-VEGF injections, specifically **bevacizumab**, in the treatment of Coats' disease. The trial will compare this treatment to the reference treatment of laser photocoagulation over a period of six months. The study is structured to include multiple visits, beginning with an inclusion visit where participants are screened based on specific criteria, such as being 16 years or younger, having a confirmed diagnosis of Coats' disease at stages 2 or 3, and being naïve to any ocular treatment on the affected eye. Participants must also have the consent of both holders of parental authority and be beneficiaries of a Social Security scheme.

Following the inclusion visit, participants will undergo a series of follow-up visits at 2, 4, 6, and 9 months after the initiation of the study treatment. These visits are designed to assess the primary endpoint, which is the proportion of patients showing improvement in at least one stage of the disease according to the Shields classification, six months after treatment initiation. Secondary endpoints include comparisons between the two treatment groups regarding disease stage improvement, visual acuity, macular thickness, and the number of patients requiring additional treatment. The trial will also monitor adverse events and calculate the kappa coefficient to measure agreement between expert evaluators.

The expected duration of participant involvement is up to nine months, with the trial estimated to conclude by October 2026. Conditions that may lead to early termination from the study include the progression to stage 5 of the disease, the need for surgical treatment, or any serious adverse event as determined by the investigator. The trial is not classified as low intervention and is categorized as a phase 4 exploratory clinical trial. The study aims to provide valuable insights into the treatment of Coats' disease, potentially influencing future therapeutic approaches.

The clinical trial involves the administration of **Avastin** (bevacizumab), a **concentrate for solution for infusion**. Avastin is provided at a concentration of 25 mg/ml and is intended for **intravitreal use**. The active substance, bevacizumab, is a protein of non-human origin, specifically classified under "Protein - Other." The maximum daily dose of Avastin is 1.25 mg, with a total maximum dose of 6.25 mg over the course of the treatment. The treatment period is limited to a maximum of six months. The administration schedule and dosage are determined based on the specific requirements of the study protocol, ensuring adherence to the defined treatment regimen.

In addition to the experimental treatment with Avastin, the study includes a comparator treatment involving **laser photocoagulation**. This standard-of-care therapy serves as a reference treatment to evaluate the efficacy of Avastin in the management of Coats' disease. The trial is designed to assess the impact of intravitreal anti-VEGF injections as an initial and adjuvant treatment compared to the established laser photocoagulation method. Participant compliance with the treatment regimen is monitored throughout the study to ensure accurate and reliable data collection.

Efficacy in this clinical trial will be assessed by evaluating the impact of **bevacizumab** (Avastin®) on the progression of Coats' disease. The primary endpoint is the proportion of patients who exhibit improvement in at least one stage of the disease according to the Shields classification, measured 6 months after the initiation of study treatment. Secondary endpoints include a comparison between the treatment groups regarding the proportion of patients with stage improvement assessed through multimodal retinal imaging at 2, 4, and 9 months. Additional secondary endpoints involve evaluating specific items defining the Shields stage, such as the presence of telangiectasia, exudates, retinal detachment, glaucoma, and bulbar phthisis at 2, 4, 6, and 9 months.

Visual acuity, expressed in logMAR, will be compared between the groups at 4, 6, and 9 months in children of verbal age. Macular thickness variation, presence of serous detachment, and maximum thickness of fibrosis will be assessed using optical coherence tomography at 2, 4, 6, and 9 months. The number of patients requiring additional treatment and the number of adverse events, including progression to stage 5, need for surgical treatment, cataract, vitreoretinal fibrosis, and tractional retinal detachment, will also be compared between the groups at 9 months. The kappa coefficient will be calculated to measure the agreement between two independent expert ophthalmologists evaluating the Coats' disease stage at 0, 1, 2, 4, 6, and 9 months.