Evaluation of Recombinant Human Plasma Gelsolin in Moderate-to-Severe Acute Respiratory Distress Syndrome Due to Pneumonia or Other Infections

The primary objective of this study is to assess the **efficacy** of intravenous recombinant human plasma gelsolin (rhu-pGSN) in combination with standard of care (SOC) compared to placebo plus SOC in subjects diagnosed with moderate-to-severe Acute Respiratory Distress Syndrome (ARDS) due to pneumonia or other infections. This evaluation is clinically relevant as ARDS is a critical condition with high morbidity and mortality, and effective treatments are limited. The study aims to determine if rhu-pGSN can improve patient outcomes in this severe condition.

Secondary objectives include: - **Efficacy**: To further assess the efficacy of IV rhu-pGSN versus placebo in subjects with moderate-to-severe ARDS due to pneumonia or other infections. - **Safety**: To evaluate the safety profile of IV rhu-pGSN in the same patient population. These secondary objectives are crucial for understanding the broader impact and safety of rhu-pGSN as a potential therapeutic option for ARDS.

The clinical trial involves a total of **228 participants** diagnosed with **Acute Respiratory Distress Syndrome (ARDS)** due to pneumonia or other infections. The study population includes both male and female subjects, aged 18 years and older, who are experiencing moderate-to-severe ARDS, characterized by a P/F ratio of ≤150. Participants were selected based on the presence of infection followed by documented bilateral infiltrates or opacities consistent with ARDS, as assessed by medical professionals. The trial includes individuals who are intubated for mechanical ventilation or receiving noninvasive ventilation. Participants are required to have clear evidence of a precipitating infection within the week preceding the ARDS diagnosis. Lifestyle considerations include the requirement for female subjects of childbearing potential to use two medically accepted birth control methods, and male subjects with partners who might become pregnant to use reliable contraception. The trial population is considered vulnerable, and informed consent is obtained from the subject, next of kin, or legal proxy.

The clinical trial is a **Phase II**, randomized, double-blind, placebo-controlled study designed to evaluate the efficacy and safety of adjunctive **recombinant human plasma gelsolin** (rhu-pGSN) in combination with standard of care for patients with moderate-to-severe **Acute Respiratory Distress Syndrome (ARDS)** due to pneumonia or other infections. The trial aims to compare the outcomes of rhu-pGSN plus standard of care against a placebo plus standard of care. The primary endpoint is the assessment of all-cause mortality at Day 28 between the treatment groups. Secondary endpoints include ventilator-free days through Day 28, all-cause mortality at Day 60, and the proportion of surviving subjects without respiratory support at various time points.

The trial is expected to commence recruitment on November 1, 2024, and conclude by November 29, 2026. Participants will be involved in the study for a maximum treatment period of 6 days, with follow-up assessments extending to Day 60. The study visits will include an initial screening visit to confirm eligibility based on criteria such as documented bilateral infiltrates consistent with ARDS, acute hypoxemic respiratory failure, and age of 18 years or older. Informed consent must be obtained from the subject or their legal proxy. Follow-up visits will be conducted to monitor the efficacy and safety outcomes, including the incidence of serious adverse events and laboratory abnormalities.

Participants may be withdrawn from the study if they experience significant adverse events or if they no longer meet the inclusion criteria. The study will ensure that all subjects adhere to contraceptive measures during the trial and for a specified period after the final treatment. The trial's design and methodology are structured to provide robust data on the potential benefits of rhu-pGSN in treating ARDS, with a focus on both efficacy and safety outcomes.

The clinical trial involves the administration of **Recombinant Human Plasma Gelsolin** (rhu-pGSN), which is provided in the form of a **powder for solution for infusion**. This investigational medication is intended for intravenous infusion. The dosing regimen specifies a maximum daily dose of 24 mg/kg and a total maximum dose of 84 mg/kg over a treatment period of up to 6 days. The active substance, **human plasma gelsolin, recombinant**, is a protein derived from other protein sources. The investigational product is manufactured by BioAegis Therapeutics Inc. and is identified by the European Medicinal Product number PRD11280569. The primary objective of the trial is to evaluate the efficacy and safety of rhu-pGSN as an adjunctive treatment in subjects with moderate-to-severe acute respiratory distress syndrome (ARDS) due to pneumonia or other infections.

The study also includes a **placebo** control, which consists of a 0.9% saline solution. The placebo is administered in a manner identical to the investigational product, serving as a comparator to assess the efficacy of the rhu-pGSN treatment. The placebo is not associated with any active pharmaceutical ingredients and is used to maintain the double-blind nature of the trial. Participants receiving the placebo will follow the same administration schedule as those receiving the investigational product, ensuring consistency in the study protocol.

The efficacy of the investigational treatment in this clinical trial will be assessed using several primary and secondary endpoints. The primary endpoint is the comparison of **all-cause mortality** at Day 28 between the treatment groups. Secondary endpoints include the number of ventilator-free days through Day 28, all-cause mortality at Day 60, and the proportion of surviving subjects without respiratory support at Day 28. Additionally, the time to death and the proportions of subjects dying over time (Days 7, 14, and 28) will be evaluated, as well as the proportion of surviving subjects without respiratory support over time (Days 7, 14, and 28). The time to discontinuation of respiratory support and the proportions without respiratory support over time (Days 7, 14, and 28) will also be assessed. For subjects not intubated at entry, the frequency of intubation through Day 28 will be compared between treatment groups. The number of days spent in the ICU and in the hospital through Day 28, as well as the frequency of renal replacement therapy (RRT) through Day 28, will be evaluated.