Evaluation of Recombinant Human Interferon Gamma 1b for Reducing Secondary Infections in ICU Patients with Sustained Immunosuppression

The primary objective of this study is to demonstrate the benefit of a standardized immunotherapy with **Interferon gamma-1b** versus placebo on the incidence of secondary infections at three months (Day 90) in ICU patients with documented sustained **immunosuppression**. This is clinically relevant as it addresses the prevention of secondary infections, which are a significant concern in patients with compromised immune systems, particularly those in intensive care units.

Secondary objectives include:

• Reduction of ICU and Day-90 mortality.
• Reduction of ICU and hospital length of stay.
• Reduction of antibiotic and antifungal consumption at Day 90.
• Biological immune restoration at Day 10.
• Cost-consequence and cost-effectiveness analyses.
• To describe the safety of Interferon gamma-1b.

The clinical trial involves a study population of **adult patients** who are hospitalized in the Intensive Care Unit (ICU) with documented **sustained immunosuppression**. The trial includes both male and female participants, with an age range that encompasses adults and older adults. The participants are selected based on specific criteria, including a minimum ICU stay of one week, an expected ICU stay of more than ten days, and at least one episode of multiple organ failure, as indicated by a SOFA score of 6 or higher. Immunosuppression is defined by specific laboratory markers, including HLA-DR and lymphopenia levels. Participants must be affiliated with the social security system, and those of childbearing potential are required to use contraception. The trial population is considered vulnerable, and informed consent must be obtained from the patient or their legal representative. The sponsor has not provided the total number of participants involved in the study.

The clinical trial is designed to evaluate the efficacy of **recombinant human interferon gamma 1b** in preventing secondary infections in patients with **sustained immunosuppression** acquired in the intensive care unit (ICU). This is a randomized, double-blind, controlled trial comparing the active treatment with a placebo. The trial is expected to commence recruitment in June 2025 and conclude by October 2028, with a total duration of approximately three years. Participants will be involved in the study for a maximum treatment period of nine days, with follow-up assessments extending to Day 90.

Study visits are structured to ensure comprehensive monitoring and data collection. The inclusion visit, or screening, will confirm eligibility based on criteria such as ICU hospitalization for at least one week, expected ICU stay beyond ten days, and documented immunosuppression. Following randomization, participants will receive either the active treatment or placebo via subcutaneous injection. Follow-up visits will occur at regular intervals to assess primary and secondary endpoints, including the incidence of secondary infections, ICU mortality, and immune restoration. The end-of-study visit at Day 90 will finalize data collection and evaluate long-term outcomes.

Participant involvement is expected to last until Day 90, with conditions for early termination including withdrawal of consent, adverse events, or protocol non-compliance. The primary endpoint is the incidence of secondary infections at three months, validated by an independent adjudication committee. Secondary endpoints include ICU mortality, length of stay, antibiotic consumption, and healthcare costs. The trial aims to provide robust evidence on the potential benefits of immunotherapy in this patient population.

The clinical trial involves the administration of two treatments, one of which is **CHLORURE DE SODIUM 0,9 % LAVOISIER**, a **solution for infusion**. This product contains the active substance **sodium chloride** and is manufactured by LABORATOIRES CHAIX ET DU MARAIS. The pharmaceutical form is a solution for infusion, and it is administered via **subcutaneous injection**. The maximum daily dose is 0.5 ml, with a total maximum dose of 2.5 ml over a treatment period of up to 9 days. This treatment is not a pediatric formulation and is used as a comparator in the trial.

The second treatment is **IMUKIN 2 X 106 UI (0,1 mg)**, a **solution for injection** containing **recombinant human interferon gamma 1b**. This product is provided by CLINIGEN HEALTHCARE B.V. and is also administered via **subcutaneous injection**. The maximum daily dose for this treatment is 0.1 mg, with a total maximum dose of 0.5 mg over a treatment period of up to 9 days. This treatment is not a pediatric formulation and serves as the experimental medication in the trial. The objective of the trial is to evaluate the efficacy of this immunotherapy in reducing the incidence of secondary infections in ICU patients with documented sustained immunosuppression.

Efficacy in this clinical trial will be assessed primarily through the **incidence of secondary infection episodes** at three months (Day 90), which will be validated by an independent adjudication committee using standardized definitions, such as the CDC surveillance definitions from January 2024. Secondary endpoints include all-cause ICU mortality and mortality at Day 90, length of stay in the ICU and hospital at Day 90, antibiotic and antifungal consumption at Day 90, and the percentage of biological immune restoration at Day 10, defined as an HLA-DR > 13,500 Ab/c and an absolute lymphocyte count > 1200/mm³. Additional secondary endpoints involve healthcare costs at Day 90, cost per secondary infection avoided, cost per additional survivor, isolation requirements, antibiotic resistance, and the rate of serious adverse reactions and suspected unexpected serious adverse reactions (SUSAR) at Day 90.