Evaluation of Bosentan in the Treatment of Early Non-Arteritic Anterior Ischemic Optic Neuropathy in Acute Phase Patients

The primary objective of this study is to evaluate the effect of **bosentan** 250 mg daily for 2 months on the visual field (mean deficit) at 3 months in patients with early-stage non-arteritic acute anterior ischemic optic neuropathy (NOIAA), compared to a placebo. This is clinically relevant as it aims to determine the efficacy of bosentan in improving visual outcomes in the acute phase of this condition, potentially offering a therapeutic option for preserving vision.

Secondary objectives include:

• Assessing visual acuity at 3 months.
• Conducting anatomical (OCT) and functional (visual acuity, visual field) assessments at 6, 12, and 24 months.
• Comparing the evolution of endothelial function, atherosclerosis, and inflammation markers under treatment with bosentan 250 mg daily.
• Evaluating the nycthemeral blood pressure profile of NOIAA subjects.

The clinical trial involves participants diagnosed with the **early stage of acute non-arteritic anterior ischemic optic neuropathy**. The study population includes both male and female subjects aged 50 years and older. Participants are required to have a systolic blood pressure of at least 100 mmHg and must be affiliated with or benefit from a social security scheme. Non-menopausal women must have a negative pregnancy test and use effective contraception throughout the study. The trial does not include a vulnerable population. The sponsor has not provided information regarding the total number of participants. Participants were selected based on specific inclusion criteria, including the recent onset of visual field alteration, with or without a painless drop in visual acuity, and associated with pale or white papilledema. The diagnosis of Horton's disease must be ruled out. Lifestyle considerations such as diet and physical activity are not specified in the available data.

The clinical trial is designed to evaluate the effects of **bosentan** in the management of patients with early-stage acute non-arteritic anterior ischemic optic neuropathy. This study is a randomized, double-blind, placebo-controlled trial, aiming to assess the impact of bosentan 250 mg daily over a period of two months. The primary objective is to evaluate the effect on the visual field (mean deficit) at three months. The trial is expected to conclude by December 4, 2027, with recruitment having started on August 4, 2015.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, blood pressure, and recent onset of visual field alteration. Following the screening, participants will be randomized to receive either bosentan or a placebo. The study includes follow-up visits to monitor visual acuity, optic fiber layer thickness, and inflammation biomarkers, among other secondary endpoints. The end-of-study visit will assess the primary and secondary outcomes, including the quality of life and the rate of bilateralization of the contralateral eye.

The expected length of participant involvement is approximately eight weeks, corresponding to the maximum treatment period. Conditions that may lead to early termination from the study include adverse reactions to the medication, withdrawal of consent, or any significant protocol deviations. The trial is conducted under strict adherence to ethical guidelines, ensuring the safety and well-being of all participants throughout the study duration.

The clinical trial involves the administration of **Bosentan**, a chemical compound, as the experimental medication. Two formulations of Bosentan are utilized: Bosentan/Mylan 125 mg and Bosentan/Mylan 62.5 mg, both in the form of film-coated tablets. The active substance in both formulations is **bosentan**, classified under the ATC code C02KX01. The pharmaceutical form is consistent across both dosages, ensuring uniformity in administration. The route of administration for both formulations is oral. The maximum daily dose for the 125 mg formulation is 250 mg, with a total maximum dose of 14,000 mg over the treatment period. For the 62.5 mg formulation, the maximum daily dose is 62.5 mg, with a total maximum dose of 3,500 mg. The treatment period for both formulations is set at a maximum of 8 weeks.

In addition to the experimental medication, a placebo is used as a comparator treatment in the study. The placebo is administered in a manner identical to the experimental medication to ensure blinding and maintain the integrity of the trial. The dosing schedule for the placebo matches that of the Bosentan formulations, with administration occurring daily over the same 8-week period. Participant compliance is monitored through regular assessments and adherence checks to ensure accurate data collection and analysis.

The efficacy of the clinical trial will be assessed by evaluating the effect of **bosentan** on patients with early non-arteritic acute anterior ischemic optic neuropathy (NOIAA). The primary endpoint for efficacy evaluation is the average deficit in automated visual field 30/2, measured in decibels. Secondary endpoints include the thickness of the optic fiber layer in SD OCT of the affected eye, visual acuity using the ETDRS scale, and visual field parameters. Additionally, the trial will assess inflammation biomarkers such as RANTES, MCP-1, TNF-α, INF-γ, IL-6, IL-10, and TGF, as well as daytime and nighttime blood pressure values and variations at baseline. Other secondary endpoints include automated visual field measurements for both the healthy and NOIAA-affected eyes, plasma assay for prepro-endothelin, the rate of bilateralization of the contralateral eye at 24 months, and a quality of life questionnaire using the French version of VFQ-25.

The efficacy parameters will be collected and analyzed at specified timepoints, including baseline and at 3 months, to determine the impact of bosentan 250 mg daily for 2 months compared to placebo. The tools and instruments involved in these assessments include automated visual field tests, SD OCT, and the ETDRS scale for visual acuity. The trial is designed to provide a comprehensive evaluation of bosentan's efficacy in managing NOIAA, with a focus on both clinical and patient-reported outcomes.