A Study to Investigate GB-0895 Adjunctive Therapy in Adults and Adolescents With Severe Uncontrolled Asthma (SOLAIRIA-1)

This is a global, multicenter, randomized, double-blind, placebo-controlled Phase 3 study to evaluate the efficacy and safety of GB-0895 adjunctive therapy in adults and adolescents with severe uncontrolled asthma with an optional open-label extension (OLE). The trial is designed to administer GB-0895 an investigational drug or placebo, subcutaneously every 6 months.

The study is divided into several phases as described below:

• Screening/Baseline (Weeks -6 to -4)
• Run-in (Weeks -4 to 0, ±1)
• Treatment (Weeks 0 to 52)
• Follow-up (Weeks 52 to 90) or optional open-label extension (OLE) (Weeks 52 to 142, OLE includes GB-0895 treatment on Week 52 and Week 78)

Approximately 786 eligible study participants will be screened and randomized globally to receive either GB-0895 or placebo at week 0 and week 26. The safety of the participants enrolled in this trial will be carefully monitored.

• Adults and adolescents ≥ 12 and ≤ 80 years of age.
• Documented physician diagnosis of asthma for ≥ 2 years.
• Subjects must be on medium to high dose ICS for ≥ 12 months before Screening Visit 1 plus at least 1 additional asthma controller (e.g., LABA, LAMA) ≥ 3 months before Screening Visit 1 with no change in ICS or controller(s) for at least three months.
• Subjects must have a well-documented history of at least two asthma exacerbations requiring systemic corticosteroid treatment despite the use of medium-to-high dose ICS in the past 12 months before Screening Visit 1.
• Adults ≥ 18 years of age at Screening Visit 1, a pre-BD FEV1 <80% predicted at Screening Visit 1.
• Adolescents 12 to < 18 years of age at Screening Visit 1: A pre-BD FEV1 < 90% predicted OR, FEV1:Forced Vital Capacity (FVC) ratio < 0.80.
• Positive BD responsiveness test: Increase of at least 12% and 200 mL in FEV1 between 15 and 60 minutes after the administration of a short-acting β2-agonist (SABA) at least once during the screening period.
• ACQ-6 score ≥ 1.5 at the Screening Visit.
• Weight ≥40 kg at the Screening Visit 1

Exclusion criteria

• Subjects who experience a clinically significant asthma exacerbation within 12 weeks before the Screening Visit or during the run-in period and require a change in asthma maintenance therapy.
• Other concurrent respiratory disease other than asthma, including (but not limited to) current infection, bronchiectasis, pulmonary fibrosis, bronchopulmonary aspergillosis, tuberculosis, diagnosis of chronic pulmonary disease (including but not limited to emphysema and/or chronic bronchitis), or a history of lung cancer.
• Eosinophilic disease (e.g., eosinophilic granulomatosis with polyangiitis, eosinophilic esophagitis).
• Any cardiovascular, gastrointestinal, hepatic, renal, neurological, musculoskeletal, infectious, endocrine, metabolic, hematological, psychiatric, or major physical impairment that is not stable in the opinion of the Investigator and could affect subject safety, influence study findings or interpretation, or impede completion of the study.
• Clinically significant infection that is unresolved and requires systemic antibiotic, antifungal, antiparasitic, or antiviral medications preceding enrollment.
• A current malignancy or previous history of cancer within 5 years before screening.
• Clinically significant infection that is not resolved before study enrollment.
• Subjects with a known, pre-existing helminth parasitic infestation within 6 months before Screening Visit 1.
• Current smokers or subjects with a smoking history ≥10 pack-years, and subjects using vaping products, including electronic cigarettes.
• Former smokers with a smoking history of <10 pack-years and users of vaping/e-cigarette products must have stopped for at least 6 months before Screening Visit 1 to be eligible.
• Hepatitis B, C, or HIV.
• Major surgery within 8 weeks before Screening Visit 1 or planned surgical procedures requiring general anesthesia or inpatient status for >1 day during the study.
• Use of any anti-IL-5 therapy (e.g., mepolizumab, reslizumab, benralizumab, depemokimab) within 12 months before Screening Visit 1 or other monoclonal antibodies used for asthma within 4 months or 5 half-lives.
• Prior use (at any time) of any anti-TSLP or anti-TSLP receptor biologics, approved (e.g., tezepelumab) or investigational.
• Treatment with systemic immunosuppressive/immunomodulating drugs (e.g., methotrexate, cyclosporine) within 12 weeks prior to randomization.
• Receipt of an investigational biologic within 4 months or 5 half-lives, OR receipt of an investigational non-biologic within 30 days or 5 half-lives before Screening Visit 1.
• Known history of sensitivity to any component of the study treatment formulation.
• History of life-threatening anaphylaxis following any biologic therapy.
• Concurrent enrollment in another clinical study involving investigational product (IP).
• Subject has been randomized in the current study or previous GB-0895 studies.
• Any clinically meaningful abnormal finding in physical examination, vital signs, ECG, hematology, serum chemistry, or urinalysis that, in the opinion of the Investigator, may put the subject at risk, influence study results, or impede study completion.
• Cirrhosis (with or without hepatic dysfunction) or other active or clinically significant liver disease.
• Receipt of immunoglobulin or blood products within 30 days before Screening Visit 1.
• Receipt of live attenuated vaccines within 30 days before randomization and during the study, including the follow-up period.
• Receipt of the T2 cytokine inhibitor suplatast tosilate within 15 days before Screening Visit 1.
• Subjects treated with bronchial thermoplasty in the last 12 months before Screening Visit 1.
• Unwillingness or inability to follow study procedures, including poor adherence to asthma controller medications, in the opinion of the Investigator.
• Women who are pregnant, lactating, or planning to become pregnant during the study.
• History (or suspected history) of alcohol misuse or substance abuse within 2 years before Screening Visit 1.