Evaluation of Sovateltide Efficacy and Safety in Acute Cerebral Ischemic Stroke: A Randomized, Double-Blind, Placebo-Controlled Phase III Trial

The primary objective of this study is to evaluate whether **sovateltide** results in a favorable functional outcome in patients with acute cerebral ischemic stroke, as measured by a modified Rankin Scale (mRS) score of 0-2 at day 90 post-randomization. This outcome is clinically significant as it indicates minimal to no disability, which is a critical goal in stroke management to improve patient quality of life and reduce long-term healthcare burdens.

Secondary objectives include:

• Determining if sovateltide leads to a good functional outcome, assessed by a National Institute of Health Stroke Scale (NIHSS) score of less than 6 at day 90.
• Evaluating functional outcomes using the Barthel Index (BI) score of ≥90 at day 90.
• Assessing excellent functional outcomes with a modified Rankin Scale score of 0-1 at day 90.
• Monitoring changes in Quality-of-Life (QoL) using EuroQol-EQ-5D-5L and Stroke-Specific Quality of Life (SS-QOL) at days 30, 60, and 90.
• Recording the incidence of recurrent cerebral ischemic stroke within 90 days.
• Tracking mortality rates within 90 days.
• Observing the incidence of symptomatic and radiographic Intracerebral Hemorrhage (ICH) within 24 (±6) hours.
• Measuring cognitive changes at days 30 and 90 using the Montreal Cognitive Assessment (MoCA) Test.
• Identifying any adverse events (AE) or serious adverse events (SAEs) associated with sovateltide.

The clinical trial involves a total of **190 participants** diagnosed with **acute cerebral ischemic stroke**. The study population comprises adult males and females aged between 18 and 80 years. Participants were selected based on specific criteria, including the clinical or radiological confirmation of ischemic stroke, with no evidence of hemorrhage, and presentation within 24 hours of symptom onset. The trial includes individuals with a National Institutes of Health Stroke Scale (NIHSS) score of 8 to less than 20 and a Level of Consciousness score of less than 2 at screening. Both genders are represented, and the trial includes a vulnerable population. Participants are expected to be available for the full course of therapy and follow-up visits. Lifestyle factors such as diet, physical activity, or habits are not specified in the available data.

The clinical trial is designed as a **randomized**, **double-blind**, parallel, placebo-controlled phase III study to evaluate the safety and efficacy of **sovateltide** in patients with **acute cerebral ischemic stroke**. The primary objective is to determine whether sovateltide results in a good functional outcome, as assessed by a modified Rankin Scale (mRS) score of 0-2 at day 90 post-randomization. The trial is expected to commence recruitment on July 1, 2025, and conclude by May 31, 2026. Participants will be involved in the study for a maximum of 90 days post-randomization.

Eligible participants include adult males and females aged 18 to 80 years, who have experienced an ischemic stroke confirmed by clinical diagnosis and imaging, and present within 24 hours of symptom onset. The inclusion criteria require a National Institutes of Health Stroke Scale (NIHSS) score of ≥8 and <20, with a Level of Consciousness score of <2 at screening. Participants must be available to complete the full course of therapy and attend follow-up visits. The study excludes individuals with hemorrhagic stroke or those unable to comply with study procedures.

The trial involves multiple study visits, beginning with a screening visit to confirm eligibility based on the inclusion criteria. Following randomization, participants will receive either sovateltide or a matching placebo via **intravenous** injection. The primary endpoint is assessed at the end-of-study visit on day 90, where the proportion of patients achieving a good functional outcome is evaluated. Secondary endpoints include assessments of NIHSS and Barthel Index (BI) scores, quality of life changes, recurrence of ischemic stroke, and adverse events.

Participants may be withdrawn from the study if they experience significant adverse events, are unable to adhere to the protocol, or if the investigator deems it necessary for their safety. The study is conducted in compliance with ethical standards and regulatory requirements, ensuring informed consent is obtained from all participants prior to any study-related procedures.

The clinical trial involves the administration of **Sovateltide**, an investigational medication, to evaluate its safety and efficacy in patients with acute cerebral ischemic stroke. **Sovateltide** is provided in the form of an **injection** and is administered **intravenously**. The dosage is calculated based on the patient's body weight, with a maximum daily dose of **0.9 µg/kg** and a total maximum dose of **2.7 µg/kg** over the treatment period. The treatment period is limited to a maximum of **1 day**. **Sovateltide** is a protein-based compound, specifically classified as "Protein - Other," and is developed by PHARMAZZ, INC. The investigational product is also known by its synonyms, including "Sovatelitide," "IRL-1620," and "SPI-1620." Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the protocol.

The study also includes a **placebo** group, which receives a **Sovateltide matching placebo**. The placebo is designed to mimic the investigational product in appearance and administration route but does not contain the active substance. The placebo is administered in the same manner as **Sovateltide**, ensuring the double-blind nature of the trial is maintained. The use of a placebo allows for a controlled comparison to assess the true efficacy and safety of **Sovateltide** in achieving a good functional outcome in patients, as measured by the modified Rankin Scale (mRS) score at day 90 post-randomization.

The efficacy of sovateltide in patients with acute cerebral ischemic stroke will be assessed through a multicentric, randomized, double-blind, parallel, placebo-controlled phase III study. The primary efficacy endpoint is the proportion of patients achieving a good functional outcome, defined as a modified Rankin Scale (**mRS**) score of 0-2 on day 90 post-randomization. Secondary endpoints include the proportion of patients with a National Institutes of Health Stroke Scale (NIHSS) score of less than 6, a Barthel Index (BI) score of 90 or higher, and an excellent functional outcome with an mRS score of 0-1, all evaluated on day 90 post-randomization.

Additional secondary endpoints involve changes in quality of life (QoL) as measured by the EuroQol EQ-5D-5L and Stroke-Specific Quality of Life (SS-QOL) scales from baseline to days 30, 60, and 90 post-randomization. The study will also assess the proportion of patients experiencing recurrent ischemic stroke, symptomatic intracerebral hemorrhage (ICH), and radiographic ICH within specified timeframes, as well as changes in the Montreal Cognitive Assessment (MoCA) score at days 30 and 90. The occurrence of adverse events (AEs) and serious adverse events (SAEs) will also be monitored.