Evaluation of Safety, Tolerability, and Efficacy of TZ-161 in Early Acute Spinal Cord Injury: A Phase 1b/2a Randomized, Single-Blinded Clinical Trial

The primary objective of this clinical trial is to evaluate the **safety** and **tolerability** of the investigational medicinal product (IMP) plus standard of care (SOC) compared to SOC alone in adult subjects with early acute **spinal cord injury** (SCI). Additionally, the study aims to compare the efficacy of IMP plus SOC versus SOC alone in the treatment of early acute SCI, specifically focusing on the American Spinal Injury Association (ASIA) Impairment Scale (AIS) motor and sensory scores. These objectives are clinically relevant as they address the potential for improved patient outcomes in terms of safety, tolerability, and functional recovery in individuals with early acute SCI.

Secondary objectives include:

• Comparing IMP plus SOC versus SOC alone in the treatment of acute SCI concerning **spasticity** and **pain**, evaluated by the Modified Ashworth Scale (MAS) and the Brief Pain Inventory (BPI), respectively.
• Assessing the impact of IMP plus SOC versus SOC alone on the length of stay in the intensive care unit (ICU) and overall hospital stay for patients with acute SCI.

The clinical trial focuses on evaluating the safety, tolerability, and efficacy of an investigational medicinal product (IMP) plus standard of care (SOC) versus SOC alone in adult subjects with **early acute spinal cord injury** (SCI). The study population includes both male and female participants aged 18 to 65 years, with a clinical diagnosis of acute SCI. The injury must be located in the thoracic region (T1 to T12) and present as a single traumatic contusion lesion. Participants are required to have an American Spinal Injury Association (ASIA) Impairment Scale (AIS) grade of B, C, or D, with a motor score of 3 or less in at least one key muscle of a lower limb. The trial does not involve a vulnerable population. Participants must be able to provide informed consent and comply with study instructions. The sponsor has not provided information regarding the total number of participants or specific lifestyle considerations such as diet or physical activity.

The clinical trial is designed as a **single-blinded**, randomized, proof-of-concept study to evaluate the safety, tolerability, and efficacy of the investigational medicinal product (IMP) TZ-161 in combination with standard of care (SOC) compared to SOC alone in adult subjects with early acute **spinal cord injury** (SCI). The trial is structured in two phases, 1b and 2a, and is expected to span from June 2024 to June 2027. Participants will be randomly assigned to receive either the IMP plus SOC or SOC alone, with the primary objective being the assessment of treatment-emergent adverse events (AEs) and serious adverse events (SAEs) over a six-month period.

Study visits are sequenced to include an initial screening visit, where eligibility is confirmed based on criteria such as age (18-65 years), clinical diagnosis of acute SCI, and ability to administer the drug within 24 hours post-injury. Following randomization, participants will attend follow-up visits at one month (M1), three months (M3), and six months (M6) to monitor changes in the ASIA Impairment Scale (AIS) motor and sensory scores, as well as other secondary endpoints like the length of stay in the intensive care unit (ICU) and hospital. The end-of-study visit will occur at the six-month mark, concluding the participant's involvement in the trial.

Participants are expected to be involved in the study for approximately six months, with conditions for early termination including the occurrence of significant AEs or SAEs, non-compliance with study procedures, or withdrawal of consent. The trial aims to provide valuable insights into the potential benefits of combining TZ-161 with SOC in the treatment of early acute SCI, contributing to the understanding of its safety and efficacy profile.

The clinical trial involves the administration of **Relert 40 mg film-coated tablets**, which contain the active substance **eletriptan**. Eletriptan is a **5-HT1 receptor agonist** and is chemically synthesized. The pharmaceutical form of the investigational medicinal product (IMP) is a film-coated tablet, designed for **oral** administration. The specific dosage of the experimental medication is 40 mg per tablet. The frequency of administration and the dosing schedule are determined by the study protocol, although specific details are not provided in the source data. The investigational product is labeled specifically for the trial, with modifications to the outer and inner packaging to ensure compliance with study requirements.

In addition to the investigational product, the study includes a **standard-of-care (SOC) therapy** as a non-experimental treatment. The SOC is administered to all participants, serving as a comparator to evaluate the safety, tolerability, and efficacy of the investigational product in combination with SOC versus SOC alone. The trial aims to assess outcomes in adult subjects with early acute spinal cord injury (SCI), focusing on ASIA AIS motor and sensory scores. Participant compliance with the dosing regimen is monitored throughout the study to ensure adherence to the protocol and to accurately assess the investigational product's effects.

The efficacy of the investigational medicinal product (IMP) plus standard of care (SOC) versus SOC alone in the treatment of early acute Spinal Cord Injury (SCI) will be assessed using several parameters. The primary endpoint for efficacy evaluation is the incidence of treatment-emergent adverse events (AEs) and serious adverse events (SAEs) between Day 1 and Month 6. Secondary endpoints include the absolute change in Modified Ashworth Scale (MAS) and Brief Pain Inventory (BPI) scores from baseline to follow-up visits at Month 1, Month 3, and Month 6. Additionally, the difference in the length of stay in the intensive care unit (ICU) and the hospital will be measured, defined as the time from admission to discharge. The absolute change in the **ASIA Impairment Scale (AIS)** motor and sensory scores, following the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI), from baseline to follow-up visits at Month 1, Month 3, and Month 6 will also be evaluated.