Evaluation of C1 Esterase Inhibitor (Human) and Sodium Chloride in the Management of Traumatic Brain Injury: A Randomized, Double-Blind, Placebo-Controlled Trial

The primary objective of the study titled "Complement Inhibition: Attacking Overshooting Inflammation @fter Traumatic Brain Injury (CIAO@TBI)" is to evaluate the **safety** and **efficacy** of C1-INH (C1 esterase inhibitor [human]) in patients with **traumatic brain injury**. This objective is clinically relevant as it aims to address the inflammatory response following traumatic brain injury, which can exacerbate neurological damage. By assessing the potential benefits of C1-INH, the study seeks to provide insights into therapeutic strategies that could mitigate inflammation and improve patient outcomes in this context.

The clinical trial focuses on evaluating the safety and efficacy of C1-INH in patients diagnosed with **Traumatic Brain Injury**. The study population includes both male and female participants, aged over 18 years, who have a Glasgow Coma Scale (GCS) score of less than 13 and require an intracranial pressure (ICP) monitor. The trial involves a vulnerable population, indicating that special considerations are in place to ensure participant safety and ethical conduct. The sponsor has not provided information regarding the total number of participants. Participants were selected based on specific inclusion criteria, ensuring that the study targets individuals who meet the necessary medical and demographic requirements. Lifestyle factors such as diet, physical activity, and habits are not specified in the available data.

The clinical trial is designed to evaluate the **safety** and **efficacy** of **C1 esterase inhibitor (human)** in patients with **traumatic brain injury**. This study is a **randomized**, **double-blind**, and **controlled** trial, categorized as a Phase 4 study. The trial aims to assess the primary endpoint of the Therapy Intensity Level Scale, with secondary endpoints including the occurrence of Serious Adverse Events (SAE) and the Glasgow Outcome Scale Extended. The trial is expected to run from February 13, 2021, to July 1, 2025, with participant involvement lasting up to one month.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age over 18 years, a Glasgow Coma Scale (GCS) score of less than 13, and the presence of an intracranial pressure (ICP) monitor. Following successful screening, participants will be randomly assigned to receive either the investigational product, **Cinryze 500 IU powder and solvent for solution for injection**, or a placebo, **Saline Solution Basi 9 mg/ml solution for infusion**, both administered via **intravenous use**. The maximum daily dose for both products is set at 6000 IU, with a total treatment period of one day.

Throughout the trial, participants will attend follow-up visits to monitor their response to treatment and any adverse events. The end-of-study visit will conclude the participant's involvement, during which final assessments will be conducted to evaluate the outcomes of the intervention. Conditions that may lead to early termination from the study include the occurrence of severe adverse reactions or withdrawal of consent by the participant. The trial is conducted under strict regulatory compliance to ensure the integrity and reliability of the data collected.

The clinical trial involves the administration of **Cinryze 500 IU powder and solvent for solution for injection**, which contains the active substance **C1 esterase inhibitor (human)**. This experimental medication is provided in the form of a powder and solvent, which is reconstituted to form a solution for injection. The route of administration is **intravenous use**. The maximum daily dose is 6000 IU, with a total maximum dose of 6000 IU over the treatment period. The treatment period is limited to one day. The medication is manufactured by Takeda Manufacturing Austria AG and is authorized under the marketing authorization number EU/1/11/688/001. Participant compliance with the dosing schedule will be monitored throughout the trial.

In addition to the experimental treatment, the study utilizes **Saline Solution Basi 9 mg/ml solution for infusion** as a comparator treatment. This solution contains **sodium chloride** as the active substance and is administered intravenously. The pharmaceutical form is a solution for infusion, and it is produced by Laboratórios Basi – Indústria Farmacêutica, S.A. The saline solution serves as a placebo in the trial, with a maximum daily and total dose of 6000 IU, administered over a one-day treatment period. The use of saline solution allows for the assessment of the efficacy and safety of the experimental treatment by providing a baseline for comparison.

The efficacy of the clinical trial titled "Complement Inhibition: Attacking Overshooting Inflammation @fter traumatic brain injury" will be assessed using specific endpoints. The primary endpoint for evaluating efficacy is the **Therapy Intensity Level Scale**. This scale will be utilized to measure the intensity of therapy required by patients with traumatic brain injury, providing a quantitative assessment of treatment impact. Secondary endpoints include the occurrence of Serious Adverse Events (SAE) and the **Glasgow Outcome Scale Extended**, which will be used to evaluate the functional outcome and recovery of patients post-treatment.

The collection and analysis of these efficacy parameters will be conducted at predetermined intervals throughout the trial. The use of validated scales and patient-reported outcomes will ensure the reliability and accuracy of the data collected. The trial is designed to study the safety and efficacy of C1-INH in patients with traumatic brain injury, with a focus on improving clinical outcomes and reducing the intensity of required therapeutic interventions.