Evaluation of Tenecteplase Versus Acetylsalicylic Acid in Central Retinal Artery Occlusion: A Phase 3 Randomized, Double-Blind, Double-Dummy Trial

The primary objective of the study is to evaluate the effect of systemic **tenecteplase** administered within 4.5 hours of the onset of **central retinal artery occlusion** (CRAO). This is clinically relevant as CRAO is an ophthalmic emergency that can lead to significant vision loss, and timely intervention is crucial for improving visual outcomes. The study aims to determine whether tenecteplase can provide a therapeutic benefit in this acute setting compared to standard treatment options.

The clinical trial involves a total of **2 participants** diagnosed with **central retinal artery occlusion**. The study population includes both male and female subjects, aged **18 years and older**, with no specific vulnerable populations selected. Participants were chosen based on their diagnosis of non-arteritic central retinal artery occlusion, with a best-corrected visual acuity of at least 1.0 logMAR and symptoms persisting for less than 4.5 hours. The trial does not specify any particular lifestyle considerations such as diet or physical activity. The selection criteria required the ability to administer the investigational medicinal product within 4.5 hours of symptom onset, and informed written consent was obtained from all participants. Women of childbearing potential were required to confirm they were not pregnant or provide a negative pregnancy test before receiving the investigational product.

The clinical trial is designed as a **randomized**, double-blind, controlled study to evaluate the efficacy of **tenecteplase** in patients with central retinal artery occlusion. The trial involves two arms with a 1:1 block randomization: one group receiving tenecteplase 0.25 mg/kg plus placebo, and the other receiving acetylsalicylic acid (ASA) plus placebo. The primary objective is to assess the effect of systemic tenecteplase administered within 4.5 hours of symptom onset. The trial is expected to conclude by January 31, 2026, with recruitment having started on October 30, 2020.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as non-arteritic central retinal artery occlusion, age of 18 years or older, and the ability to administer the investigational medicinal product within 4.5 hours of symptom onset. Follow-up visits will occur to monitor the participants' progress and assess the primary endpoint, which is the proportion of patients achieving a best-corrected visual acuity of ≤ 0.7 logMAR in the affected eye at 30 (±5) days post-treatment. The end-of-study visit will mark the completion of the trial for each participant.

The expected duration of participant involvement is approximately 30 days, with conditions for early termination including adverse events, withdrawal of consent, or protocol non-compliance. The trial will utilize encapsulated tablets of inactive substance as a placebo, alongside the active treatments of tenecteplase and ASA. The study is conducted under strict adherence to ethical guidelines, ensuring informed consent and the safety of all participants throughout the trial duration.

The clinical trial involves the administration of **TENECTEPLASE**, a solution for injection, as the experimental medication. TENECTEPLASE is a protein-based therapeutic agent administered via **intravenous injection**. The maximum daily dose is 25 mg, with a total treatment period of one day. This medication is utilized to assess its effect on central retinal artery occlusion (CRAO) when administered within 4.5 hours of onset. Participant compliance is monitored through scheduled dosing and administration records.

**Albyl-E 75 mg enterotabletter**, containing **acetylsalicylic acid**, serves as a comparator treatment in the study. This medication is provided in the form of gastro-resistant tablets and is administered **orally**. The maximum daily dose is 300 mg, with a total treatment period of one day. The administration of Albyl-E is intended to provide a standard-of-care comparison against the experimental treatment. Compliance is ensured through pill counts and participant diaries.

The study also includes the use of **Sodium Chloride Fresenius Kabi Italia 0.9% Solution for infusion** as a placebo. This solution is administered **intravenously** and is chemically composed of sodium chloride. The maximum daily dose is 25 mg, with a total treatment period of one day. The placebo is used to maintain the double-blind nature of the trial, ensuring unbiased results. Compliance is monitored through infusion records and participant observation.

Additionally, encapsulated tablets of an inactive substance are used as a placebo in the trial. These tablets are administered **orally** and serve to maintain the double-dummy design of the study. The inactive substance ensures that participants and investigators remain blinded to the treatment allocation, thus preserving the integrity of the trial results. Compliance is tracked through pill counts and participant logs.

Efficacy in the clinical trial titled "TENECTEPLASE IN CENTRAL RETINAL ARTERY OCCLUSION STUDY (TenCRAOS)" will be assessed using the primary endpoint of the proportion of patients achieving a best-corrected visual acuity of ≤ 0.7 logMAR in the affected eye at 30 (±5) days post-treatment. This endpoint represents an improvement in best-corrected visual acuity of at least 0.3 logMAR, evaluated through an intention-to-treat (ITT) analysis. The trial involves a prospective, randomized-controlled, double-dummy, double-blind phase 3 multi-centre design, comparing **tenecteplase** 0.25 mg/kg plus placebo against acetylsalicylic acid (ASA) plus placebo, with a 1:1 block randomization. The primary endpoint will be measured at a specific timepoint, 30 days after treatment, to determine the efficacy of the intervention in improving visual acuity in patients with non-arteritic central retinal artery occlusion.