A Phase 2a, Randomized, Double-Blind, Parallel-Group, Placebo Controlled Study to Evaluate the Efficacy, Safety, and Tolerability of Fexlamose (AER 01) Inhalation Solution in the Treatment of Adults with Moderate to Severe Chronic Obstructive Pulmonary Disease

The primary objective is to evaluate the efficacy of AER-01 compared with placebo in adults with moderate to severe chronic obstructive pulmonary disease. This assessment is clinically relevant for determining the therapeutic benefit of fexlamose inhalation solution in managing disease progression and symptom control in this patient population.

The secondary objective is to assess the efficacy of AER-01 compared with placebo, providing additional supportive evidence for the clinical performance of the investigational treatment.

This clinical trial enrolled a total of **10 participants** diagnosed with **Chronic Obstructive Pulmonary Disease** (COPD). The study population consisted of both **male and female** subjects aged **40 to 80 years**. Participants were selected based on a verified diagnosis of cigarette smoking-related COPD, requiring a smoking history of at least 10 pack years and specific **spirometry** criteria including a postbronchodilator FEV1/FVC ratio below 0.70. The trial specifically targeted individuals with **moderate to severe COPD**, defined by a prebronchodilator **FEV1** between 25% and 60% of predicted normal values. All participants were required to have **whole lung emphysema** percent below 40% as determined by CT lung scan analysis. Enrolled subjects were maintained on stable **inhaled bronchodilator** medications for at least 4 weeks prior to screening, with no more than 2 COPD exacerbations requiring hospitalization in the previous year. The study included a **vulnerable population**.

This is a Phase 2a, randomized, double-blind, parallel-group, placebo-controlled clinical trial designed to evaluate the efficacy, safety, and tolerability of Fexlamose (containing 6-thio-alfa-d-glucopyranosyl 6-thio-alfa-d-glucopyranoside) inhalation solution in adults with moderate to severe chronic obstructive pulmonary disease (COPD). The study employs a parallel-group design in which participants are randomly assigned to receive either the active investigational medicinal product or placebo. Both the participants and the investigators remain blinded to the treatment assignment throughout the study duration. The investigational product is administered via inhalation using the eFlow Nebulizer Handset and eBase Controller Kit, a CE-marked medical device. The placebo inhalation solution is manufactured as a sterile, single-dose, preservative-free aqueous solution. The maximum treatment period is 28 days.

The primary objective of the trial is to evaluate the efficacy of Fexlamose compared with placebo. The primary endpoint is the change from baseline in prebronchodilator forced expiratory volume in one second (FEV1) at Week 4. Secondary endpoints include change from baseline in computed tomography (CT) mucus plugging subscore (MPSS) at Week 4, percentage of participants who have treatment-related reduction of MPSS, change from baseline in St. George's Respiratory Questionnaire for COPD (SGRQ-C) at Week 4, percentage of participants with at least 4 unit decrease from baseline in SGRQ-C at Week 4, change from baseline in prebronchodilator forced vital capacity (FVC) at Week 4, change from baseline in oxygen saturation (SpO2) at Week 4, incidence of adverse events throughout the study, hematology, biochemistry, and urinalysis parameters assessed throughout the study, and incidence of ground-glass opacity (GGO) as detected by CT lung scan at Week 4.

Participants eligible for enrollment must be male or female aged 40 to 80 years with a verified diagnosis of cigarette smoking-related COPD. Participants must be current or former smokers with a history of at least 10 pack years of cigarette smoking and have a postbronchodilator FEV1/FVC ratio less than 0.70. Moderate to severe COPD is defined as a prebronchodilator FEV1 that is greater than 25% and less than 60% of predicted normal at Visit 1. Participants must meet specific spirometry performance criteria for acceptability and repeatability at screening visits, and the baseline FEV1 at Visit 3 must be within the greater of 12% or 100 mL of the mean FEV1 obtained at the two screening visits. Participants must have whole lung emphysema percent less than 40% based on automated analysis of the CT lung scan. Participants must be on stable maintenance inhaler medications for COPD with no dose adjustments for at least 4 weeks prior to screening and during the screening period, including an inhaled bronchodilator. Participants must have had no more than 2 COPD exacerbations requiring hospitalization in the past year.

The study involves multiple visits beginning with screening assessments at Visit 1 and Visit 2 to confirm eligibility and establish baseline measurements. Visit 3 serves as the baseline visit where treatment is initiated. Follow-up visits occur at Week 4 to assess efficacy and safety endpoints. The expected length of participant involvement is approximately 4 weeks of active treatment. Conditions that may lead to early termination from the study include the occurrence of adverse events, failure to meet protocol requirements, withdrawal of consent, or at the discretion of the investigator if continuation poses a risk to the participant. The estimated recruitment start date is February 27, 2026, with an estimated study end date of December 12, 2026.

The experimental treatment consists of **Fexlamose** (AER-01), an **inhalation solution** containing the active substance **6-thio-alfa-d-glucopyranosyl 6-thio-alfa-d-glucopyranoside**, which is of chemical origin. The product is manufactured by AER Therapeutics Inc. and is administered via the **inhalation route**. The treatment is delivered using the **eFlow Nebulizer Handset & eBase Controller Kit**, a CE-marked medical device manufactured by TÜV Süd. The eFlow Nebuliser System has been tested in multiple clinical trials and is intended to administer investigational drug products as an aerosol. The device is similar to the eFlow rapid medical device, which has been available on the European market since May 2005. The maximum treatment period for Fexlamose administration is **28 days**. Fexlamose is formulated as a sterile, single-dose preparation for inhalation use in adults with **moderate to severe chronic obstructive pulmonary disease**.

The **placebo** comparator is an inhalation solution manufactured as a **sterile, single-dose, preservative-free aqueous solution**. The placebo does not contain any active pharmaceutical ingredient and serves as the control treatment in this randomized, double-blind, parallel-group study. The placebo is administered via the same inhalation route as the experimental treatment to maintain blinding and ensure comparability of treatment groups.

Efficacy will be assessed using multiple parameters measured at baseline and Week 4. The primary endpoint is the change from baseline in prebronchodilator forced expiratory volume in one second (FEV1) at Week 4. Secondary efficacy endpoints include the change from baseline in computed tomography (CT) mucus plugging subsegmental score (MPSS) at Week 4, the percentage of participants who have treatment-related reduction of MPSS, the change from baseline in St. George's Respiratory Questionnaire for chronic obstructive pulmonary disease (COPD) patients (SGRQ-C) at Week 4, the percentage of participants with a decrease of at least 4 units from baseline in SGRQ-C at Week 4, the change from baseline in prebronchodilator forced vital capacity (FVC) at Week 4, and the change from baseline in oxygen saturation (SpO2) at Week 4. Additional assessments include the incidence of ground-glass opacities (GGO) as detected by CT lung scan at Week 4. Spirometry assessments will be performed according to standardized acceptability and repeatability criteria, with baseline predose FEV1 required to be within the greater of 12% or 100 mL of the mean FEV1 obtained at the two screening visits. CT lung scans will utilize automated analysis to evaluate emphysema and mucus plugging parameters.