Evaluation of Amikacin Liposome Inhalation Suspension in Combination Therapy for Mycobacterium xenopi Pulmonary Infection: A Randomized Controlled Trial

The primary objective of this study is to demonstrate the **superiority** of ARIKAYCE, an amikacin liposome inhalation suspension, when added to a standard treatment regimen, in terms of achieving a 3-month sputum conversion rate in patients with **Mycobacterium xenopi pulmonary infection** (MX-PD), compared to the standard regimen alone. This is clinically relevant as achieving sputum conversion is a critical marker of treatment efficacy and can significantly impact patient outcomes by reducing the bacterial load and potentially improving respiratory function.

Secondary objectives include evaluating the time to culture conversion, assessing the rate of culture conversion at 6 months, and determining the 12 and 24 months mortality rates. These objectives are important for understanding the long-term efficacy and safety of the treatment regimen, as well as its impact on patient survival and disease progression.

The clinical trial focuses on participants diagnosed with **Mycobacterium xenopi pulmonary infection**. The study population includes both male and female subjects aged 18 years and older. Participants are required to meet the 2020 ATS/ERS/ESCMID/IDSA criteria for nontuberculous mycobacterial pulmonary infection, which includes specific clinical and microbiological criteria. The trial does not involve a vulnerable population. The sponsor has not provided information regarding the total number of participants. Selection criteria emphasize the presence of respiratory symptoms and specific radiological findings, as well as microbiological confirmation of the infection. Lifestyle factors such as diet and physical activity are not specified as considerations for this study. The trial aims to assess the efficacy of adding ARIKAYCE to a standard treatment regimen in improving the 3-month sputum conversion rate compared to the standard regimen alone.

The clinical trial is designed to evaluate the efficacy of **ARIKAYCE** liposomal 590 mg nebuliser dispersion in the treatment of **Mycobacterium xenopi pulmonary infection**. This is a prospective, controlled, open-label, randomized study aimed at demonstrating the superiority of ARIKAYCE when added to a standard treatment regimen, compared to the standard regimen alone. The primary endpoint is the 3-month sputum conversion rate, with secondary endpoints including 6-month sputum conversion rate, recurrence, failure, relapse, cure, death, and safety. The trial is expected to commence recruitment on July 1, 2024, and conclude by March 1, 2030.

The trial involves a randomized, controlled design where participants are assigned to either the test group receiving ARIKAYCE or a comparator group receiving standard antibiotics such as **rifampicin**, **amoxicillin**, and **ethambutol hydrochloride**. The study is not blinded, allowing both participants and investigators to know the treatment assignments. The trial will span a maximum treatment period of 6 to 12 months, depending on the specific medication regimen.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age (18 years or older) and specific clinical and microbiological criteria for nontuberculous mycobacterial pulmonary infection. Follow-up visits will be scheduled to monitor treatment response and safety, with assessments including sputum culture tests and imaging studies. The end-of-study visit will evaluate the final outcomes and any long-term effects of the treatment.

Participant involvement is expected to last up to 12 months, with conditions for early termination including adverse events, withdrawal of consent, or failure to adhere to the study protocol. The trial is structured to ensure rigorous monitoring and data collection to support the evaluation of ARIKAYCE's therapeutic efficacy and safety in treating Mycobacterium xenopi pulmonary infection.

The clinical trial involves the administration of **ARIKAYCE** liposomal 590 mg nebuliser dispersion, which contains the active substance **amikacin**. This experimental medication is administered via **inhalation use**. The maximum daily dose is 590 mg, with a total dose not exceeding 590 mg per day. The treatment period is set for a maximum of 6 months. The pharmaceutical form is a nebuliser dispersion, and the product is classified as an antibiotic. Participant compliance with the dosing schedule will be monitored throughout the trial.

**Rifampicin** is used as a comparator treatment in this study. It is administered orally in a pharmaceutical form identified as PHF00170MIG. The dosage is calculated based on body weight, with a maximum daily dose of 10 mg/kg and a total dose not exceeding 10 mg/kg per day. The treatment period for rifampicin is up to 12 months. This medication is also classified as an antibiotic.

Another comparator treatment is **amoxicillin**, administered orally in a pharmaceutical form identified as PHF00009MIG. The maximum daily dose is 1000 mg, with a total dose not exceeding 1000 mg per day. The treatment period is set for a maximum of 12 months. Amoxicillin is classified as an antibiotic, and participant compliance will be monitored.

**Ethambutol hydrochloride** is also used as a comparator treatment. It is administered orally in the form of a film-coated tablet. The dosage is based on body weight, with a maximum daily dose of 15 mg/kg and a total dose not exceeding 20 mg/kg per day. The treatment period is up to 6 months. This medication is classified as an antibiotic, and compliance with the dosing schedule will be monitored throughout the trial.

The efficacy of the clinical trial will be assessed by evaluating the **sputum conversion rate** in patients with Mycobacterium xenopi pulmonary infection. The primary endpoint is the 3-month sputum conversion rate, which will be used to demonstrate the superiority of ARIKAYCE addition to a standard treatment compared to the standard regimen alone. Secondary endpoints include the 6-month sputum conversion rate, recurrence, failure, relapse, cure, death, and safety. These endpoints will be measured and collected at specified timepoints throughout the trial duration. The analysis will focus on comparing the outcomes between the treatment groups to confirm the therapeutic efficacy of the interventions.