Efficacy and Safety Evaluation of Inhaled Molgramostim in Pediatric Patients with Autoimmune Pulmonary Alveolar Proteinosis

The primary objective of this clinical study is to evaluate the **efficacy** of inhaled molgramostim in pediatric participants diagnosed with **autoimmune pulmonary alveolar proteinosis** (aPAP), aged from 6 years to less than 18 years. This objective is clinically relevant as it aims to determine the therapeutic potential of molgramostim in improving the health outcomes of children affected by this rare and serious lung condition, which is characterized by the accumulation of surfactant in the alveoli, leading to impaired gas exchange and respiratory distress.

The secondary objective is to investigate the **safety** of inhaled molgramostim in the same pediatric population. Assessing safety is crucial to ensure that the treatment does not pose undue risks to the participants, thereby supporting its potential use in clinical practice for managing aPAP in children.

The clinical trial involves participants diagnosed with **autoimmune pulmonary alveolar proteinosis** (aPAP), specifically targeting a pediatric population aged from 6 years to less than 18 years. Both male and female subjects are included in the study, and the trial acknowledges the involvement of a vulnerable population due to the age range. The sponsor has not provided the total number of participants. The selection criteria require participants to have a confirmed history of pulmonary alveolar proteinosis, verified through lung biopsy, bronchoalveolar lavage cytology, or high-resolution computed tomography of the chest, along with a positive serum anti-GM-CSF autoantibody test. Additionally, participants must have a hemoglobin-adjusted diffusing capacity of the lung for carbon monoxide (DLCO) of 70% or less, as predicted at screening. The study does not specify any particular lifestyle considerations such as diet or physical activity for the participants.

The clinical trial is designed to evaluate the **efficacy** and safety of inhaled **molgramostim** in pediatric subjects diagnosed with **autoimmune pulmonary alveolar proteinosis** (aPAP). This is a phase 3, open-label, multicenter study. The trial will involve participants aged 6 to less than 18 years, with a confirmed diagnosis of aPAP. The study will be conducted over an estimated period from June 2025 to August 2027, with a maximum treatment duration of 48 weeks for each participant. The trial will assess the primary endpoint of change in hemoglobin-adjusted percentage predicted diffusing capacity of the lung for carbon monoxide (DLCO) from baseline to week 24. Secondary endpoints include changes in DLCO at week 48, oxygen saturation, 6-minute walk distance, Pediatric Quality of Life scores, and pulmonary function tests, among others.

Participants will undergo a series of study visits, beginning with a screening visit to confirm eligibility based on inclusion criteria such as age, history of aPAP, and positive serum anti-GM-CSF autoantibody test results. Following the screening, eligible participants will commence treatment with inhaled molgramostim. Follow-up visits will be scheduled at regular intervals to monitor safety and efficacy outcomes, including assessments at weeks 4, 12, 24, 48, and a final end-of-study visit at week 52. The expected length of participant involvement is approximately 52 weeks, including the treatment and follow-up periods.

Conditions that may lead to early termination from the study include the occurrence of adverse events that compromise participant safety, non-compliance with study procedures, or withdrawal of consent. The study is not categorized as low intervention, and it is essential that all procedures adhere to the protocol to ensure the integrity of the trial data. The trial will be conducted in accordance with ethical standards and regulatory requirements, ensuring the safety and well-being of all participants throughout the study duration.

The clinical trial involves the administration of **Molgramostim**, an experimental medication formulated as a **solution for inhalation**. This investigational product is developed by Serendex Pharmaceuticals A/S and is designated as an orphan drug under the identifier OD/106/12. The active substance, molgramostim, is administered via inhalation, with a maximum daily dose of 300 micrograms and a total maximum dose of 100,800 micrograms over a treatment period of up to 48 weeks. The primary objective of the trial is to evaluate the efficacy and safety of inhaled molgramostim in pediatric subjects aged 6 to less than 18 years with **autoimmune pulmonary alveolar proteinosis** (aPAP).

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are utilized. The trial is open-label, meaning that both the researchers and participants are aware of the treatment being administered. Participant compliance with the dosing schedule is monitored throughout the study to ensure adherence to the prescribed regimen. The trial is designed to assess the therapeutic potential of molgramostim in a pediatric population, with careful monitoring of safety and efficacy outcomes.

The efficacy of inhaled Molgramostim in pediatric subjects with **Autoimmune Pulmonary Alveolar Proteinosis (aPAP)** will be assessed through a series of primary and secondary endpoints. The primary endpoint is the change in hemoglobin (Hb)-adjusted percentage predicted diffusing capacity of the lung for carbon monoxide (DLCO) from baseline to week 24. Secondary endpoints include the change in Hb-adjusted % predicted DLCO from baseline to week 48, absolute change from baseline in oxygen saturation (SpO2) at rest after 24 and 48 weeks of treatment, and absolute change from baseline in 6-minute walk distance (6MWD) after 24 and 48 weeks of treatment. Additional secondary endpoints involve changes from baseline in the Pediatric Quality of Life (PedsQLTM) Generic Core Scale score after 24 and 48 weeks, adverse events (AEs) including clinically significant findings on pulmonary function tests, titers of anti-GM-CSF antibodies at baseline and after 4, 12, 24, 48, and 52 weeks, and changes from baseline in forced expiratory volume in one second (FEV1) (% predicted) and forced vital capacity (FVC) (% predicted) after 24 and 48 weeks of treatment.