Dose-Ranging Study of LQ036 Single-Domain Antibody Nebulization Solution in Poorly Controlled Asthma

A Phase IIb, Randomized, Double-Blind, Placebo-Controlled, Multicenter Clinical Trial to Evaluate the Safety and Efficacy of LQ036 Single-Domain Antibody Nebulization Solution in Patients With Poorly Controlled Asthma

What is the goal of this study? The goal of this clinical trial is to find out whether the study drug LQ036 (a nebulized solution taken by inhaling through a nebulizer) works to improve lung function and asthma control in people whose asthma is not well controlled. The study will also learn about the safety of LQ036, how the body processes it, and whether the body develops an immune response to it.

What are the main questions?

The most important question is:

• Does LQ036 improve lung function (measured by FEV₁ - the amount of air you can blow out in one second) more than a placebo at Week 12?

Other important questions include:

• Does LQ036 improve lung function at other time points (weeks 1, 2, 4, 8, 16, 20, 24)?
• Does LQ036 reduce asthma attacks (sudden worsening of asthma that needs extra treatment)?
• Does LQ036 help people use less rescue medication (inhaler for quick relief) and have more days without asthma symptoms?
• Does LQ036 improve scores on asthma control and quality of life questionnaires?
• What medical problems do participants have when taking LQ036?

The study includes four periods: a screening period of up to 2 weeks to check eligibility, followed by a 2 week run in period during which all participants take a placebo once daily by nebulizer and record symptoms and rescue medication use. Participants are then randomly assigned to one of three groups for the 24 week treatment period: LQ036 12 mg, LQ036 24 mg, or placebo once daily. For the first 12 weeks, the LQ036 groups are compared with the placebo group; after 12 weeks, those originally on placebo are reassigned to either LQ036 12 mg or 24 mg for the remaining 12 weeks. Throughout the study period, all participants continue their usual asthma controller medicines. A 4 week safety follow up visit occurs after the 24 week treatment to monitor for side effects.

Inclusion Criteria:

• Outpatients, aged 12 to 75 years inclusive, male or female, with body mass index (BMI) between 18 and 30 kg/m² inclusive. For participants aged 12 to 17 years, body weight must be ≥30 kg.
• Diagnosed with bronchial asthma according to the 2025 Global Initiative for Asthma (GINA) guidelines prior to screening, with a documented history of asthma for ≥12 months.
• For at least 3 months prior to screening, the participant has used inhaled corticosteroids (ICS) combined with at least one controller medication, and has maintained a stable treatment regimen and dosage for at least 1 month prior to screening. Low, medium, and high maintenance doses of ICS are defined according to the 2025 GINA guidelines (if multiple nebulized or combined administration methods are used, doses are to be combined).
• At screening, pre-bronchodilator FEV₁ is ≥40% and <80% of the predicted normal value. For participants on low-dose ICS, pre-bronchodilator FEV₁ is ≥40% and <85% of the predicted normal value.
• At screening, Asthma Control Questionnaire-5 (ACQ-5) score ≥1.5.
• At screening, a positive bronchodilator reversibility test (increase in FEV₁ of ≥12% and an absolute increase of ≥200 mL, 15-30 minutes after inhalation of 400 μg salbutamol). If the reversibility test does not reach the positive threshold, one additional test is permitted within 7 days (excluding the day of the initial test). Alternatively, documented evidence of a positive bronchodilator reversibility test within 2 years prior to screening is acceptable.
• At screening, blood eosinophil (EOS) count ≥150 cells/μL or fractional exhaled nitric oxide (FeNO) ≥25 ppb.
• Experienced ≥1 severe exacerbation within the 12 months prior to screening (not required for participants on low-dose ICS).
• Participants fully understand the purpose, nature, methods, and possible adverse reactions of the study, voluntarily agree to participate, and sign the informed consent form before any study procedures begin.
• At randomization, pre-bronchodilator FEV₁ has increased by ≤20% from the screening value, and remains ≥40% and <80% of the predicted normal value (for participants on low-dose ICS, pre-bronchodilator FEV₁ is ≥40% and <85% of the predicted normal value).
• At randomization, ACQ-5 score ≥1.5.
• During the run-in period, participant compliance with run-in medication and background medication is ≥80% and ≤120%, compliance with daily diary completion is ≥80%, and there are complete data for at least 4 days within the 7 days prior to randomization.

Exclusion Criteria:

• Life-threatening asthma, defined as an asthma episode requiring intubation within 1 year prior to screening or during the run-in period, and/or a history of hypercapnia, respiratory arrest, hypoxic seizures, asthma-related syncopal episodes, etc.
• Experienced a severe asthma exacerbation within 1 month prior to screening.
• History of allergy to biologics, or known hypersensitivity to any component of the investigational product.
• Use of biologics (including but not limited to anti-IgE, anti-IL-5, anti-IL-5 receptor, anti-IL-4/13 receptor, anti-TSLP monoclonal antibodies, etc.) and/or systemic immunosuppressants (including but not limited to methotrexate, cyclosporine, mycophenolate mofetil, tacrolimus, penicillamine, sulfasalazine, hydroxychloroquine, azathioprine, cyclophosphamide) for inflammatory diseases within 8 weeks or 5 half-lives (whichever is longer) prior to screening.
• Received intravenous immunoglobulin (IVIG) or allergen-specific immunotherapy (SIT) within 3 months prior to screening.
• Received systemic corticosteroids (excluding topical, ophthalmic, or intranasal corticosteroids), antibiotics, antifungals, antivirals, antiparasitic drugs, non-selective beta-blockers, or herbal medicines with anti-asthmatic effects within 1 month prior to screening or during the run-in period.
• Received live or attenuated vaccine within 3 months prior to screening, or plan to receive live or attenuated vaccine during the study period.
• Underwent bronchial thermoplasty within 12 months prior to screening.
• Underwent major surgery within 8 weeks prior to screening, or plans to undergo surgery requiring general anesthesia or hospitalization for >1 day during the study period.
• In the investigator's judgment, presence of respiratory diseases other than asthma, including but not limited to chronic obstructive pulmonary disease (COPD), asthma-COPD overlap syndrome (ACOS), or any other significant lung disease (e.g., active pneumonia, idiopathic pulmonary fibrosis, pneumothorax, atelectasis, pulmonary fibrosis, bronchopulmonary dysplasia, bronchiectasis, etc.), that may place the participant at undue risk or affect the evaluation of study results.
• Based on imaging and investigator judgment, presence of active tuberculosis or non-tuberculous mycobacterial infection, untreated latent tuberculosis, or history of incompletely treated tuberculosis.
• Active autoimmune disease or autoimmune disease requiring immunosuppressive therapy, such as rheumatoid arthritis, inflammatory bowel disease, primary biliary cirrhosis, systemic lupus erythematosus, multiple sclerosis, etc.
• Blood EOS >1500 cells/μL at screening, or other systemic diseases that may cause elevated peripheral blood EOS count (e.g., hypereosinophilic syndrome, eosinophilic granulomatosis with polyangiitis, eosinophilic esophagitis, etc.), which in the investigator's judgment may affect the evaluation of the drug.
• Known or suspected immunodeficiency, including history of invasive opportunistic infection (e.g., histoplasmosis, listeriosis, coccidioidomycosis, pneumocystosis, aspergillosis) even if resolved; or presence of unusually frequent, recurrent, or prolonged infections suggestive of an immunocompromised state.
• Known parasitic infection, or suspected or high-risk parasitic infection in the investigator's judgment.
• Active infection (e.g., upper respiratory tract infection) within 1 month prior to screening or during the run-in period, or acute infection requiring systemic anti-infective therapy.
• History of lymphoproliferative disease or malignancy (participants with basal cell carcinoma, localized squamous cell carcinoma of the skin, or cervical carcinoma in situ are eligible if they have completed curative treatment and have had no evidence of recurrence for at least 12 months prior to signing informed consent), or other medical history that in the investigator's judgment may affect the evaluation of the drug.
• Presence of any other severe and/or uncontrolled disease or treatment that, in the investigator's judgment, may affect the evaluation of the drug, including but not limited to: severe neurological disease, severe mental disorder, uncontrolled diabetes mellitus, uncontrolled hypertension, major cardiovascular disease, corrected QT interval prolongation (male >450 ms, female >470 ms, Fridericia's formula), or persistent arrhythmia.
• Current smoker or cessation of smoking for <6 months; or former smoker with a smoking history of ≥10 pack-years (pack-years = [cigarettes per day / 20] × years of smoking).
• Positive serology for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody, human immunodeficiency virus antibody, or Treponema pallidum antibody at screening (participants with positive HBsAg but HBV-DNA below the lower limit of detection, or positive HCV antibody but HCV-RNA below the lower limit of detection, are eligible).
• Participants with severe liver or kidney dysfunction, such as aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >3 × upper limit of normal (ULN), or serum creatinine >1.5 × ULN.
• Pregnant or breastfeeding women; women planning to become pregnant during the study or within 3 months after the end of the study; fertile women or men who, in the investigator's judgment, cannot use medically accepted reliable contraception from signing informed consent until 3 months after the last dose of study drug; positive pregnancy test result at screening or before randomization for fertile women.
• Participation in another clinical study of a drug or device within 3 months prior to signing informed consent, with use of investigational drug/device; or still within the follow-up period of another clinical study or within 5 half-lives of the investigational drug (whichever is longer) at the time of signing informed consent.
• History of blood donation or significant blood loss, blood transfusion, or use of blood products within 3 months prior to screening.
• Known or suspected non-compliance, drug abuse, substance abuse, or alcohol abuse (daily pure alcohol intake >40 g for males, >20 g for females).
• Any condition that, in the investigator's judgment, makes the participant unsuitable for participation in this clinical trial.