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

Prior treatment

• Subjects who experience a clinically significant asthma exacerbation within 12 weeks before the Screening Visit or during Run-in period and require a change in asthma maintenance therapy may not be enrolled.
• Major surgery within 8 weeks before Screening Visit 1 or planned surgical procedures requiring general anesthesia or inpatient status for >1 day during the conduct of the study.
• Use of any anti-IL-5 therapy (e.g., mepolizumab, reslizumab, benralizumab, depemokimab) in the 12 months before Screening Visit 1 or other previous monoclonal antibodies used for the treatment of asthma (e.g., dupilimab, omalizumab) within 4 months or 5 half-lives, whichever is longer, before Screening Visit 1.
• Prior use (at any time) of any anti-TSLP or anti-TSLP receptor biologics, approved or investigational.
• Treatment with the following medications within the last 12 weeks before randomization: Systemic immunosuppressive/immunomodulating drugs (e.g., methotrexate, cyclosporine) except for OCS used in the treatment of asthma/asthma exacerbations. Maintenance OCS of prednisone ≤10 mg/day (or equivalent) for asthma is allowed if the dose has been stable for ≥3 months before screening and is not planned to be weaned or changed over the 52-week treatment period.
• Concurrent enrollment in another clinical study involving an IP.
• The subject has been randomized in the current study or in previous GB-0895 studies.
• Concurrent Respiratory Disease: Presence of a known pre-existing, clinically important lung condition other than asthma. This includes (but is not limited to) current infection, bronchiectasis, pulmonary fibrosis, bronchopulmonary aspergillosis, tuberculosis, or diagnosis of chronic obstructive pulmonary disease (including but not limited to emphysema and/or chronic bronchitis) or a history of lung cancer. NOTE: Subjects with known or suspected active tuberculosis disease (pulmonary or extrapulmonary) are excluded from study participation. TB screening is not required by the protocol but may be performed in accordance with local regulations, guidelines, or investigator judgment. Subjects with a history of treated latent or active TB may be eligible, provided that there is no evidence of active disease and the subject successfully completed treatment at least 12 months prior to the first dose.
• Hepatitis B or Hepatitis C: i. Screening for Hepatitis B Virus (HBV) includes HBV surface antigen (HBsAg), HBV surface antibody (anti-HBs), and HBV core antibody total (anti-HBc total) (Section 15.4). Excluded if positive for hepatitis B surface antigen (HBsAg). Subjects testing positive for hepatitis B core antibody (anti-HBc-total) but negative for hepatitis B surface antibody (anti-HBs) must have further testing for HBV DNA. If HBV DNA is detectable, or if this test cannot be performed, or if there is evidence of chronic liver disease, subject will be excluded. ii. Subjects with chronic Hepatitis C Virus (HCV) infection are excluded. Subjects with a previous HCV infection (HCV antibody-positive) and have documented viral load (HCV RNA) that is undetectable can be included if there is evidence of 2 undetectable HCV RNA tests at least 12 weeks apart, 1 of which may include a test performed at Screening.
• Receipt of immunoglobulin or blood products within 30 days before Screening Visit 1.
• Receipt of live attenuated vaccines 30 days before the date of randomization and during the study including follow-up period.
• Receipt of the T2 cytokine inhibitor Suplatast tosilate within 15 days before Screening Visit 1.
• Subjects who have been treated with bronchial thermoplasty in the last 12 months before Screening Visit 1.
• Unwillingness or inability to follow the study procedures, including poor adherence to asthma controller medications, in the opinion of the Investigator.
• Clinically significant infection that requires systemic antibiotic, antifungal, antiparasitic or antiviral medications within 14 days before enrollment or during the Run-in Period.
• Clinically significant, acute, unresolved illness within 7 days before randomization (Day 1). Note: randomization may be delayed for full recovery if acceptable to the Investigator.
• Helminth parasitic infection: Subjects with a known, pre-existing helminth parasitic infestation within 6 months before Screening Visit 1.
• Current smokers or subjects with 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 or e-cigarette products must have stopped for at least 6 months before Screening Visit 1 to be eligible.

Other illness

• History of known immunodeficiency disorder including a positive human immunodeficiency virus (HIV) test at Screening Visit 1, or the subject is taking antiretroviral medications as determined by medical history and/or subject’s verbal report.
• Known history of sensitivity to any component of the study treatment formulation or a history of drug or other allergy that, in the opinion of the Investigator or Medical Monitor, contraindicates their participation.
• History of life-threatening anaphylaxis following any biologic therapy.
• Eosinophilic Diseases: Subjects with other conditions that could lead to elevated EOS such as hyper-eosinophilic syndromes including (but not limited to) eosinophilic granulomatosis with polyangiitis (formerly known as Churg-Strauss syndrome) or eosinophilic esophagitis.
• Any disorder, including, but not limited to, 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: a. Affect the safety of the subject throughout the study. b. Influence the findings of the study or the interpretation. c. Impede the subject's ability to complete the entire duration of study.
• Malignancy: A current malignancy or previous history of cancer within 5 years before Screening (subjects that had localized carcinoma of the skin which, or in situ carcinoma of the cervix that were resected for cure, will not be excluded).

Lab values

• Any clinically meaningful abnormal finding in physical examination, vital signs, electrocardiogram (ECG), hematology, serum chemistry, or urinalysis, which in the opinion of the Investigator, may put the subject at risk because of his/her participation in the study, or may influence the results of the study, or the subject's ability to complete the entire duration of the study.
• Cirrhosis (with or without evidence of hepatic dysfunction) or other active or clinically significant liver disease (including aspartate transaminase, alanine transaminase, or alkaline phosphatase >2 times the upper limit of normal (ULN) or total bilirubin >1.5 times the ULN) will be excluded. Subjects with total bilirubin >1.5 times the ULN with Gilbert’s syndrome (isolated unconjugated hyperbilirubinemia) are permitted if no additional hepatic abnormalities are present.

Other

• Receipt of investigational biologic within 4 months or 5 half-lives, OR receipt of investigational non-biologic within 30 days or 5 half-lives before Screening Visit 1
• Involvement in the planning and/or conduct of the study (applies to Generate or PPD staff and/or study site staff) or subjects employed by or relatives of the employees of the study site or Sponsor.
• Women who are pregnant, lactating or who plan to become pregnant during the study are not eligible.
• A history (or suspected history) of alcohol misuse or substance abuse within 2 years before Screening Visit 1.

• Adults and adolescents ≥12 and ≤80 years of age at the time of signing the informed consent/assent.
• Subjects must have a documented physician diagnosis of asthma for ≥2 years that meets the National Heart, Lung, and Blood Institute guidelines or Global Initiative for Asthma (GINA) guidelines.
• Subjects with documented physician requirement for daily medium- to high-dose ICS for ≥12 months before Screening Visit 1 plus at least 1 additional controller (e.g., LABA, LAMA) ≥3 months before Screening Visit 1 with no change in ICS or controller(s) for at least 3 months. NOTE: Subjects treated with ICS-formoterol as maintenance and reliever must have received this treatment for ≥12 months before Screening Visit 1 with no change in the ICS dose for at least 3 months.
• Subjects must have a well-documented history of at least 2 asthma exacerbations requiring systemic corticosteroid treatment despite the use of medium-to-high dose ICS in the past 12 months before Screening Visit 1.
• Airflow obstruction as indicated by: o For adults ≥18 years of age at Screening Visit 1, a pre-BD FEV1 <80% predicted (Global Lung Initiative 12 [GLI 12*]) recorded at Screening Visit 1. o For adolescents 12 to <18 years of age at Screening Visit 1: ▪ A pre-BD FEV1 <90% predicted (GLI 12*) recorded at Screening Visit 1 OR ▪ FEV1: Forced Vital Capacity (FVC) ratio <0.80 recorded at Screening Visit 1 * In regions where GLI 12 is not considered standard, other references ranges may be used.
• Positive BD responsiveness test: Increase of at least 12% and 200 mL in FEV1 between 15 and 60 minutes after the administration of a SABA (according to American Thoracic Society [ATS]/European Respiratory Society [ERS] guidelines) at least once during the Screening period. NOTE: If the subject does not have a positive BD responsiveness test it may be repeated once during the screening period provided the subject demonstrated ≥9% increase in FEV1 between 15 and 60 minutes after the administration of a SABA. OR Well-documented evidence of positive BD responsiveness test obtained ≤18 months prior to Screening visit.
• ACQ-6 score ≥1.5 at BOTH the Screening and Randomization visits.
• Weight ≥40 kg at the Screening Visit 1