Evaluation of Human Plasma Proteins with ≥96% Albumin and Glutathione (Reduced), Sodium Salt in Decompensated Cirrhosis Patients

The primary objective of this study is to evaluate the impact on effective **albumin** concentration and the safety of administering the reHA solution compared to the standard commercial human albumin (HA) solution in patients with decompensated cirrhosis who require long-term albumin treatment. This is clinically relevant as it aims to determine whether the reHA solution can provide a safer or more effective treatment option for managing decompensated cirrhosis, a condition characterized by severe liver dysfunction and associated complications.

The secondary objectives are to assess the impact of the reHA solution on several clinical outcomes and surrogate markers of efficacy related to the pathophysiological drivers of decompensated cirrhosis. These assessments are crucial for understanding the broader clinical benefits and potential mechanisms of action of the reHA solution in this patient population.

The clinical trial involves participants diagnosed with **decompensated cirrhosis**, a condition characterized by liver dysfunction. The study population includes both male and female subjects, aged between 18 and 85 years. Participants are required to have a diagnosis of liver cirrhosis of any etiology, with specific criteria for ascites severity and diuretic treatment. The trial does not include a vulnerable population. The sponsor has not provided information regarding the total number of participants. Participants were selected based on their medical condition and the need for long-term albumin treatment. Lifestyle factors such as diet and physical activity are not specified as part of the selection criteria.

The clinical trial is designed to evaluate the **safety** and efficacy of a human albumin solution with a restored structural profile in patients with **decompensated cirrhosis**. This is a Phase IV, randomized, double-blind, controlled trial. The primary objective is to assess the impact on effective albumin concentration and the safety of the administration of the reHA solution compared to the standard commercial HA solution. The trial is expected to commence on January 1, 2025, and conclude by December 31, 2026, with a total duration of approximately two years.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as a diagnosis of liver cirrhosis of any etiology and specific ascites grades. Following randomization, participants will attend follow-up visits at 1, 3, and 6 months to monitor primary endpoints, including effective albumin concentration and safety parameters such as adverse events. Secondary endpoints will involve assessing organ function parameters at these intervals. The end-of-study visit will occur at the 6-month mark, concluding the participant's involvement.

The expected length of participant involvement is six months, during which they will receive treatment via **IV infusion**. Conditions that may lead to early termination from the study include the occurrence of serious adverse events or non-compliance with the study protocol. The trial will ensure rigorous monitoring of safety and efficacy signals throughout the participant's involvement, adhering to the highest standards of clinical research methodology.

The clinical trial involves the administration of **Albunorm 20%**, a **solution for infusion** containing **human plasma proteins with not less than 96% albumin**. This pharmaceutical product is manufactured by Octapharma Italy S.P.A. and is authorized under the marketing authorization number 039187063. The solution is administered via **intravenous infusion**. The maximum daily dose is 80 grams, with a total maximum dose of 1000 grams over a treatment period of up to 6 months. The primary objective of the trial is to evaluate the impact on effective albumin concentration and the safety of this solution in patients with decompensated cirrhosis who require long-term albumin treatment.

Another experimental medication used in the trial is **RITION Glutatione**, a **solution for injection** containing **glutathione (reduced), sodium salt**. This product is produced by PIAM Farmaceutici SPA and holds the marketing authorization number 027300060. It is also administered via **intravenous infusion**. The maximum daily dose for this medication is 1.84 grams, with a total maximum dose of 23 grams over a 6-month treatment period. Both medications are tested for their efficacy and safety in the context of the trial, with no additional non-experimental treatments, such as standard-of-care therapy or placebo, being utilized.

The efficacy of the clinical trial will be assessed through a series of primary and secondary endpoints. The primary endpoints include the measurement of effective **albumin** concentration at 1, 3, and 6 months from randomization. Additionally, the safety of the reHA solution will be evaluated over the 6-month treatment period by monitoring vital signs, laboratory parameters, and recording any adverse events (AEs) or serious adverse events (SAEs). The percentage of subjects experiencing at least one AE, SAE, or adverse drug reaction (ADR) will be documented, along with the total number of these events.

Secondary endpoints will focus on signals of efficacy by comparing various parameters at 1, 3, and 6 months from randomization. These parameters include organ function assessments such as liver function, which will be evaluated using the grade of ascites (according to the International Club of Ascites criteria), grade of hepatic encephalopathy (HE) using the West Haven classification and Animal Naming Test, as well as bilirubin and albumin serum levels. Renal function will be assessed through blood urea nitrogen (BUN), serum creatinine, electrolytes, and estimated glomerular filtration rate (eGFR) using the CKD-EPI equation.