Evaluation of Rezafungin Acetate for Chronic Pulmonary Aspergillosis in Patients with Limited Treatment Options: A Phase 2, Open-Label Study

The primary objective of this study is to evaluate the **effectiveness** of a 6-month regimen of **rezafungin** in the treatment of **chronic pulmonary aspergillosis (CPA)** in patients with limited treatment options. This evaluation will be based on clinical and radiological responses, as measured by the St George's Respiratory Questionnaire (SGRQ), weight, and computed tomography (CT) imaging. The clinical relevance of this objective lies in addressing the therapeutic needs of CPA patients who have restricted treatment alternatives, potentially improving their respiratory function and quality of life.

Secondary objectives include: - Evaluating the effectiveness of 3- and 6-months’ rezafungin in the treatment of CPA in subjects with limited treatment options. - Assessing the **safety** and **tolerability** of rezafungin in these patients. These objectives are crucial for understanding the broader implications of rezafungin use, including its potential as a viable long-term treatment option and its safety profile in a vulnerable patient population.

The clinical trial involves a total of **30 participants** diagnosed with **chronic pulmonary aspergillosis (CPA)**. The study population includes both male and female subjects aged 18 years and older. Participants were selected based on their inability to receive systemic azole antifungal therapy and the necessity for antifungal treatment due to radiological changes or a high burden of symptoms. The trial includes individuals who are considered a vulnerable population. Participants must be willing and able to provide written informed consent. Female subjects of child-bearing potential must adhere to strict birth control measures or abstain from sexual activity, while male subjects must agree to use barrier methods or be vasectomized, and refrain from sperm donation during and after the study period. The trial does not specify any particular lifestyle considerations such as diet or physical activity. The sponsor has not provided additional information regarding the general health status of the participants.

The clinical trial is a **phase 2**, multicentre, open-label, single-arm study designed to evaluate the effectiveness and safety of **rezafungin acetate** in the treatment of **chronic pulmonary aspergillosis (CPA)** in patients with limited treatment options. The trial aims to assess the clinical and radiological response over a period of six months, utilizing the St George's Respiratory Questionnaire (SGRQ), weight measurements, and computed tomography (CT) imaging as primary endpoints. Secondary endpoints include changes in Aspergillus IgG levels, respiratory symptom scores, and the frequency of echinocandin-resistant isolates, among others. The trial is expected to commence recruitment on June 1, 2025, and conclude by July 31, 2026.

Participants will be involved in the study for a maximum of 26 weeks, during which they will receive **REZZAYO 200 mg powder for concentrate for solution for infusion** via **intravenous use**. The study will begin with an inclusion (screening) visit to confirm eligibility based on criteria such as age, established diagnosis of CPA, and inability to receive systemic azole antifungal therapy. Following the screening, participants will undergo regular follow-up visits at three and six months to monitor treatment efficacy and safety, including assessments of adverse events (AEs) and serious adverse events (SAEs). The end-of-study visit will mark the completion of the treatment period, where final evaluations will be conducted.

Participant involvement may be terminated early if they experience significant adverse reactions, fail to comply with study protocols, or if the investigator deems it necessary for the participant's safety. The trial is not categorized as low intervention, and it is conducted under the therapeutic exploratory and confirmatory clinical trial category. The investigational medicinal product is packaged in a manner that provides protection from light, as demonstrated by a photostability study, ensuring the integrity of the drug throughout the trial duration.

The clinical trial involves the administration of **REZAFUNGIN ACETATE**, marketed under the name REZZAYO, which is a **powder for concentrate for solution for infusion**. This investigational medicinal product is intended for the treatment of chronic pulmonary aspergillosis (CPA) in patients with limited treatment options. The pharmaceutical form is a solution for infusion, and the route of administration is **intravenous use**. The dosage regimen includes a maximum daily dose of 400 mg, with a total maximum dose of 5.40 g over the treatment period. The treatment duration is set for a maximum of 26 weeks. The vials containing the drug product are individually packed in a white cardboard carton, which provides protection from light, as confirmed by a photostability study. The secondary packaging used for the investigational product is slightly thicker than that used for the commercial product.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are specified. The focus is solely on evaluating the effectiveness and safety of rezafungin in the specified patient population. Participant compliance with the dosing schedule will be monitored throughout the trial to ensure adherence to the treatment protocol. The investigational product is not a pediatric formulation and is classified under the ATC code J02AX, indicating its use as an **antimycotic for systemic use**. The active substance, rezafungin acetate, is of semi-synthetic origin and categorized as a protein - other. The study aims to assess clinical and radiological responses using tools such as the St George's Respiratory Questionnaire (SGRQ), weight measurements, and computed tomography (CT) imaging.

The efficacy of rezafungin in the treatment of chronic pulmonary aspergillosis (CPA) will be assessed through a combination of clinical, radiological, and patient-reported outcomes. The primary endpoints include the St George’s Respiratory Questionnaire (SGRQ), which evaluates quality of life changes as reported by patients, weight changes, and computed tomography (CT) thoracic scans to assess radiological improvement. These CT changes will be evaluated by independent radiologists experienced in diagnosing CPA.

Secondary endpoints will further explore efficacy by measuring changes in Aspergillus IgG levels, weight, SGRQ scores, Respiratory Symptom scores, and EQ-5D-5L scores at 3 and 6 months from baseline. Additional secondary measures include the need for changes in antibiotic or steroid prescriptions, the absence of persistently positive respiratory samples for **Aspergillus** spp., changes in the frequency of echinocandin-resistant isolates, and hospitalizations attributed to deterioration in any category. Safety and tolerability will also be assessed through the nature and severity of adverse events (AEs) and serious adverse events (SAEs), as well as physical examinations and laboratory tests conducted at 3 and 6 months.