Evaluation of Recombinant Human Interferon Gamma 1b as Adjunctive Therapy in Candidemia Patients

The primary objective of this study is to evaluate the **efficacy** and safety of recombinant interferon-gamma 1b (rIFN-γ) as an adjunctive treatment in combination with standard therapy for patients with **candidemia**. Efficacy is defined by the clearance of candidemia within the first 7 days of treatment, considering mortality. This is clinically relevant as candidemia is a serious bloodstream infection with significant morbidity and mortality, and improving treatment outcomes is crucial.

Secondary objectives include:

• Evaluating new markers that could identify patients who respond to immunotherapy with rIFN-γ.
• Identifying markers to monitor the patient's immunological and clinical response to rIFN-γ immunotherapy.
• Performing mechanistic studies to elucidate mechanisms important for host defense against candidemia and the effects of rIFN-γ on these mechanisms.

The clinical trial involves a total of **75 participants** diagnosed with **candidemia**, a bloodstream infection caused by Candida species. The study population includes both **males and non-pregnant females** who are 18 years of age or older. Participants were selected based on specific criteria, including having at least one positive blood culture for Candida species and clinical evidence of infection within 120 hours prior to enrollment. The trial population is characterized by individuals who may present with symptoms such as fever, low blood pressure, or signs of inflammation at an infected site. Participants are required to agree to use barrier methods of contraception during the study period, and women of childbearing age must have a negative pregnancy test at baseline. The study does not specify any particular lifestyle considerations such as diet or physical activity. The trial includes a vulnerable population, ensuring that informed consent is obtained from all subjects or their legal representatives.

The clinical trial is designed to evaluate the **efficacy** and safety of **recombinant human interferon gamma 1b** as an adjunctive treatment in combination with standard therapy for patients with **candidemia**. This study is a randomized, double-blind, controlled trial, conducted over an estimated duration from January 2022 to September 2025. Participants will be randomly assigned to receive either the investigational product or a placebo, in addition to standard therapy. The primary endpoint is the time to first negative blood culture, with secondary endpoints including time to resolution of infection, treatment success rates, overall survival at day 28, and the incidence of treatment-emergent adverse events.

Study visits are structured to ensure comprehensive monitoring and data collection. The inclusion visit, or screening, will confirm eligibility based on criteria such as age, clinical evidence of infection, and informed consent. Participants will then undergo baseline assessments before randomization. Follow-up visits will occur at regular intervals to assess clinical outcomes, collect blood samples, and monitor for adverse events. The end-of-study visit will evaluate the overall health status, including organ function and nutritional status, and collect final data on secondary endpoints.

Participant involvement is expected to last up to 28 days post-treatment, with the maximum treatment period being two weeks. Conditions that may lead to early termination from the study include withdrawal of consent, significant protocol deviations, or adverse events that compromise participant safety. The trial aims to provide valuable insights into the potential benefits of **recombinant human interferon gamma 1b** in treating **candidemia**, contributing to the optimization of therapeutic strategies for this condition.

The clinical trial involves the administration of **IMMUKINE**, a **solution for injection** containing **recombinant human interferon gamma 1b** as the active substance. This experimental medication is provided in a concentration of 2 x 10^6 International Units (IE), equivalent to 0.1 mg per dose. The pharmaceutical form is a solution intended for **subcutaneous injection**. The dosing regimen specifies a maximum daily dose of 50 micrograms per square meter (µg/m²) and a maximum total dose of 50 µg/m². The treatment period is limited to a maximum of 2 weeks. The administration of the drug is conducted under the supervision of healthcare professionals to ensure adherence to the dosing schedule and to monitor participant compliance.

In addition to the experimental treatment, participants will receive standard therapy for **candidemia** as part of the study protocol. The standard therapy serves as the comparator treatment to evaluate the efficacy and safety of the adjunctive use of **recombinant human interferon gamma 1b**. The primary objective is to assess the clearance of candidemia within the first 7 days of treatment, considering mortality as a factor. The study is designed to ensure that all participants receive the best available standard-of-care treatment in conjunction with the investigational drug.

The efficacy of the clinical trial evaluating **recombinant human interferon gamma 1b** (rIFN-Gamma 1b) as an adjunctive treatment for candidemia will be assessed through several primary and secondary endpoints. The primary endpoint is the time to the first negative blood culture, indicating the clearance of candidemia within the first 7 days of treatment. Secondary endpoints include the time of resolution to infection, percentage of patients with mycological outcomes at the end of standard therapy (EOST), end of treatment (EOT), and at days 14 and 28 after EOT, as well as the percentage of patients with treatment success at these same timepoints. Overall survival at Study Day 28 and the number of patients with Treatment Emergent Adverse Events (TEAEs) will also be evaluated.

Additional secondary endpoints involve the evaluation of patient status at the end of rIFN-Gamma treatment, including organ (dys)function assessed by the Sequential Organ Failure Assessment (SOFA) score, and adverse events. Nutritional status will be monitored through body weight, BMI, and nutritional blood parameters such as prealbumin, total lymphocytes, and cholesterol. The study will also explore genetics and transcriptomics, gut microbiota composition, Candida genomics and metabolomics, and changes in circulating cytokines, biomarkers, LAP activation, inflammasome, and immunoprofiling. These parameters will be measured and collected at specified timepoints throughout the trial to comprehensively assess the efficacy of the treatment regimen.