Phase 3 Randomized Double‑Blind Placebo‑Controlled Trial of Subcutaneous GB‑0895 as Adjunctive Therapy in Adults and Adolescents with Severe Uncontrolled Asthma

The primary objective is to determine whether subcutaneous GB-0895, given as adjunctive therapy, reduces the rate of clinically significant asthma exacerbations over 52 weeks compared with placebo in patients with severe uncontrolled asthma, addressing a key driver of morbidity and healthcare utilization in this high‑risk population.

• Evaluate the effect of GB-0895 on clinically significant asthma exacerbations over 52 weeks in participants with elevated baseline eosinophil counts.
• Assess lung function, health‑related quality of life, and asthma control measures in the GB-0895 group versus placebo.

The trial enrolled 725 participants, comprising both male and female individuals aged 12 to 80 years, who were classified as having severe uncontrolled asthma. Subjects were required to have a physician‑confirmed asthma diagnosis for at least two years, be on a stable regimen of daily medium‑ to high‑dose inhaled corticosteroids plus at least one additional controller for a minimum of three months, and demonstrate a documented history of at least two systemic corticosteroid‑treated exacerbations in the preceding year. Eligibility also required evidence of airflow limitation (pre‑bronchodilator FEV₁ < 80 % predicted in adults or < 90 % predicted in adolescents, or an FEV₁/FVC ratio < 0.80), a positive bronchodilator response (≥12 % and 200 mL increase in FEV₁), an ACQ‑6 score ≥ 1.5 at screening and randomization, and a body weight of at least 40 kg. Participants were selected based on these clinical and functional criteria to ensure a population with persistent, inadequately controlled disease despite optimized standard therapy; no specific lifestyle restrictions such as diet or physical activity were stipulated beyond maintaining a stable medication regimen.

The study is a Phase 3 randomized, double-blind, placebo-controlled trial evaluating the adjunctive use of subcutaneous GB-0895 (300 mg) versus 0.9 % sodium chloride in adults and adolescents with severe uncontrolled asthma. Eligible participants aged 12–80 years with a documented asthma diagnosis, persistent high‑dose inhaled corticosteroid therapy, a history of at least two systemic‑corticosteroid‑requiring exacerbations in the previous year, and demonstrated bronchodilator responsiveness undergo a screening visit to confirm inclusion criteria. Following successful screening, subjects are randomized at a baseline visit and receive the first study injection; subsequent visits are scheduled throughout the 52‑week treatment period to monitor efficacy, safety, lung function, and patient‑reported outcomes. The primary endpoint is the annualized asthma exacerbation rate of clinically significant events over 52 weeks, with secondary endpoints including changes in pre‑bronchodilator FEV₁, Asthma Quality of Life Questionnaire, Asthma Control Questionnaire, time to first exacerbation, and daily symptom diary scores. The overall trial recruitment window spans from June 2026 to December 2028, and each participant remains in the study for approximately one year, concluding with an end‑of‑study visit at Week 52.

The investigational product, GB-0895, is supplied as a sterile injection for administration by subcutaneous route. Each dose contains 300 mg of the active substance and is delivered as a single‑use injection. Dosing is performed according to the study schedule, with each administration recorded in the dosing log and overseen by qualified clinical staff.

The control arm receives a matching placebo consisting of 0.9 % sodium chloride solution. The placebo is administered in an identical manner to the investigational product, using a subcutaneous injection to maintain blinding. The volume and appearance of the placebo are matched to GB‑0895 to ensure comparability.

All study drug administrations occur at the designated study visits, and adherence to the dosing schedule is monitored through electronic case report forms and site‑maintained compliance records. Any deviations from the prescribed schedule are documented and reported in accordance with protocol‑defined procedures.

The primary efficacy assessment will be the Annualized asthma exacerbation rate (AAER) of clinically significant exacerbations over a 52‑week treatment period. Clinically significant exacerbations are defined as events requiring systemic corticosteroids (oral, intravenous, or intramuscular) and/or hospitalization or emergency department visits with systemic corticosteroid administration. Exacerbation events will be recorded continuously from randomization, and the AAER will be calculated by dividing the total number of exacerbations by the total exposure time in years for each treatment group.

Secondary efficacy evaluations include the following parameters measured at baseline and Week 52: change from baseline in pre‑bronchodilator forced expiratory volume in 1 second (FEV1) obtained by standardized spirometry; change from baseline in the Asthma Quality of Life Questionnaire (AQLQ(S)12+) score; change from baseline in the Asthma Control Questionnaire (ACQ-6) score; change from baseline in the weekly mean daily Asthma Daytime Symptom Diary (ADSD) score; and change from baseline in the weekly mean daily Asthma Nighttime Symptom Diary (ANSD) score. In addition, the time to first clinically significant exacerbation will be assessed from the date of randomization to the occurrence of the first qualifying event. All questionnaires and diaries are validated patient‑reported outcome instruments, and spirometric measurements will follow ATS/ERS guidelines. Data will be analyzed using appropriate statistical models to compare the GB‑0895 and placebo arms for each efficacy endpoint.