Phase 2 Multicenter Randomized Trial of Lenomorelin in Acute Anterior Circulation Ischemic Stroke with Endovascular Thrombectomy

The primary objective of this study is to evaluate the effect of **ghrelin** on the severity of the neurological deficit at seven days following symptom onset in patients with acute ischemic stroke due to large vessel occlusion of the anterior circulation, who have been treated with endovascular thrombectomy (EVT). This is clinically relevant as it aims to determine the potential therapeutic benefits of ghrelin in improving neurological outcomes in a critical patient population.

Secondary objectives include assessing the effects of ghrelin on various clinical parameters: - Functional outcome at 90 days - Neurological deficit at one and three days post-symptom onset - Infarct size at day 3 ± 1 - Blood glucose levels from day 1 to 7 - Blood pressure from day 1 to 7 - Temperature from day 1 to 7 - Safety, including the number of serious adverse events (SAEs) and mortality - Cognitive functioning at 90 days, measured by the telephone version of the Montreal Cognitive Assessment (t-MoCA).

The clinical trial focuses on patients diagnosed with **acute ischemic stroke** caused by large vessel occlusion of the anterior circulation. The study population includes both male and female participants aged 18 years and older. The trial does not specify the total number of participants, as the sponsor has not provided this information. Participants were selected based on specific criteria, including a clinical diagnosis confirmed by neuro-imaging, treatment with endovascular therapy (EVT), and a pre-EVT score of at least 10 on the NIH Stroke Scale (NIHSS). The trial population includes a vulnerable group, and participants must be able to commence trial treatment within six hours of stroke onset. The study does not specify any particular lifestyle considerations such as diet or physical activity.

The clinical trial is designed as a **randomized**, double-blind, controlled study to evaluate the efficacy of **acyl-ghreline** in patients with acute ischemic **stroke**. The primary objective is to assess the effect of **ghrelin** on the severity of the neurological deficit at seven days post-symptom onset in patients treated with endovascular thrombectomy (EVT). The trial will involve intravenous administration of acylated ghrelin at a dose of 600 micrograms twice daily for five days, compared to standard care. The study is expected to commence recruitment on October 1, 2024, and conclude by April 30, 2026.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as a clinical diagnosis of acute ischemic stroke due to large vessel occlusion, treatment with EVT, and a pre-EVT NIHSS score of at least 10. Neuro-imaging will be used to confirm the diagnosis and rule out intracranial hemorrhage. Eligible participants must be 18 years or older and able to provide written informed consent, with the possibility to start trial treatment within six hours of stroke onset.

Following the inclusion visit, participants will receive the investigational product or standard care and will be monitored through follow-up visits. These visits will assess primary and secondary endpoints, including NIHSS scores at various time points, mRS and Barthel index scores at 90 days, mortality, infarct size, and physiological parameters such as blood glucose, blood pressure, and body temperature. The end-of-study visit will occur at 90 days post-stroke onset, where final assessments will be conducted.

The expected duration of participant involvement is approximately 90 days. Conditions that may lead to early termination from the study include withdrawal of consent, occurrence of serious adverse events (SAEs), or any condition that, in the investigator's opinion, warrants discontinuation for the participant's safety. The trial's design ensures rigorous evaluation of the investigational product's efficacy and safety, contributing valuable data to the management of acute ischemic stroke.

The clinical trial involves the administration of **Acyl-ghreline**, an experimental medication formulated as a **lyophilisate for suspension for injection**. The active substance in this medication is **lenomorelin**, also known by its synonyms **ghrelin**, **acyl-ghrelin**, and **SUN11031**. This substance is classified as a protein of other origin. The medication is administered via **intravenous bolus injection or IV infusion**. The dosing regimen specifies a maximum daily dose of 1200 micrograms, with a total maximum dose of 6000 micrograms over a treatment period of up to 5 days. The medication is not a pediatric formulation and is not classified as an orphan drug.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are specified. The focus is solely on evaluating the effects of Acyl-ghreline in patients with acute ischemic stroke caused by large vessel occlusion of the anterior circulation, who are treated with endovascular thrombectomy. Compliance with the dosing schedule and administration route is monitored to ensure adherence to the study protocol.

Efficacy in this clinical trial will be assessed primarily by evaluating the effect of **ghrelin** on the severity of the neurological deficit in patients with acute ischemic stroke. The primary endpoint is the score on the National Institutes of Health Stroke Scale (NIHSS) at seven days (±1) after stroke onset or at discharge, if earlier. Secondary endpoints include the score on the modified Rankin Scale (mRS) at 90 days (±14) after stroke onset, the score on the Barthel Index at 90 days (±14), mortality at 90 days (±14), and scores on the NIHSS at 24 (±6) and 72 (±12) hours after stroke onset. Additional secondary endpoints are the score on the telephone version of the Montreal Cognitive Assessment (t-MoCA) at 90 days (±14), infarct size at 72 hours (±24) based on MRI measurements, and physiological parameters such as blood glucose levels, blood pressure, and body temperature at days 1-7 (or until discharge). Serious adverse events (SAEs) will also be monitored.

The planned methods for measuring these efficacy parameters include validated scales such as the NIHSS, mRS, Barthel Index, and t-MoCA. MRI will be used to assess infarct size. The schedule for collecting these data points includes specific timepoints: 24 hours, 72 hours, 7 days, and 90 days post-stroke onset. The analysis will focus on comparing the outcomes between the treatment group receiving intravenous acylated ghrelin and the standard care group. This trial aims to provide insights into the potential benefits of ghrelin in improving neurological outcomes in patients undergoing endovascular thrombectomy for acute ischemic stroke.