A Randomized, Double-Blind, Placebo-Controlled Phase Ib Study of Multiple Ascending Doses of EB070 Injection in Adults With Moderate-to-Severe Asthma

• EB070 (Biological): Anti-TSLP Monoclonal Antibody

Primary outcomes

• AEs [From the Start of Dosing Through Week 32]: including Adverse events defined by CTCAE 6.0(Common Terminology Criteria for Adverse Events version 6.0)

Secondary outcomes

• Tss_max [From Week 1 to Week 32]: The time required to reach the maximum concentration of EB070 in the bloodstream after administration at steady state.
• Css_max [From Week 1 to Week 32]: The maximum concentration of EB070 in the bloodstream during a dosing interval at steady state.
• Css_min [From Week 1 to Week 32]: The minimum concentration of EB070 in the bloodstream during a dosing interval at steady state.
• AUCss 0-t [From week 1 to week 32]: The area under the concentration-time curve of EB070 from the start to the last measurable concentration during a dosing interval at steady state.
• AUCss 0-∞ [From week 1 to week 32]: The area under the concentration-time curve of EB070 from the start of a dosing interval to infinity at steady state.
• RAUC [From week 1 to week 32]: The ratio of EB070 exposure after repeated dosing to that after a single dose.
• RCmax [From week 1 to week 32]: The ratio of the maximum EB070 concentration after repeated dosing to that after a single dose.
• CL/Fss [From week 1 to week 32]: The apparent clearance of EB070 from the bloodstream at steady state.
• Vz/Fss [From week 1 to week 32]: The apparent volume of distribution of EB070 at steady state.
• Kelss [From week 1 to week 32]: The elimination rate constant of EB070 at steady state.
• t½ss [From week 1 to week 32]: The time required for the concentration of EB070 in the bloodstream to decrease by 50% at steady state.
• MRT [From week 1 to week 32]: The mean residence time of EB070 in the body.
• CLR [From week 1 to week 32]: The renal clearance of EB070.
• FeNO [Baseline; Weeks 5, 9, 13, 17, and 21]
• Eosinophil Count [Baseline; Weeks 5, 9, 13, 17, and 21]
• IL5 Concentration [Baseline; Weeks 5, 9, 13, 17, and 21]
• IL-13 Concentration [Baseline; Weeks 5, 9, 13, 17, and 21]
• IgE Concentration [Baseline; Weeks 5, 9, 13, 17, and 21]
• Change from baseline in pre-bronchodilator (Pre-BD) forced expiratory volume in 1 second (FEV1) measured before dosing at each assessment time point [Weeks 5, 9, 13, 17, and 21]
• Change from baseline in peak expiratory flow (PEF) at each assessment time point [Weeks 5, 9, 13, 17, and 21]
• Change from baseline in Asthma Control Test (ACT) score at each assessment time point [Weeks 5, 9, 13, 17, and 21]
• Number of participants experiencing asthma exacerbations and number of asthma exacerbation episodes at each assessment time point [Weeks 5, 9, 13, 17, and 21]

Sex: All, ages: 18 Years to 75 Years

Inclusion Criteria:

* Patients with moderate-to-severe asthma who meet the diagnostic criteria specified in the 2024 Guidelines for the Prevention and Treatment of Bronchial Asthma, with a history of asthma for at least 1 year. Moderate asthma is defined as asthma that can be well controlled with Step 3 treatment, while severe asthma is defined as asthma that requires Step 4 or Step 5 treatment to achieve good control, or remains uncontrolled despite 3 months of treatment at Step 4 or Step 5.
* Male or female participants aged 18 to 75 years (inclusive) at the time of signing the informed consent form.
* A documented bronchodilator reversibility test conducted during screening or within at least 12 months prior to screening demonstrating an increase in forced expiratory volume in 1 second (FEV1) of ≥12% and an absolute increase of ≥200 mL.
* Pre-bronchodilator FEV1 ≥40% and <80% of the predicted value at screening.
* Asthma Control Test (ACT) score ≤19 prior to randomization.
* Treatment with a physician-prescribed medium- or high-dose inhaled corticosteroid (ICS) for at least 6 months prior to screening, with a stable ICS dose for at least 3 months prior to randomization.
* Concomitant treatment with at least one other asthma controller medication, such as a long-acting β2-agonist (LABA), long-acting muscarinic antagonist (LAMA), or leukotriene receptor antagonist (LTRA), with a stable dose for at least 3 months prior to randomization.
* Women of childbearing potential must have a negative serum β-human chorionic gonadotropin (β-hCG) pregnancy test within 72 hours prior to the first dose. Postmenopausal women who have been amenorrheic for at least 12 months are considered not to be of childbearing potential. Women with a documented history of hysterectomy, bilateral oophorectomy, bilateral salpingectomy, or tubal ligation are also considered not to be of childbearing potential and are not required to undergo pregnancy testing.
* Participants who understand and are willing to comply with the study procedures, voluntarily participate in the study, and provide written informed consent.

Exclusion Criteria:

* Any concomitant respiratory disease that, in the investigator's opinion, may interfere with the assessment of the safety or pharmacodynamic effects of the study drug or the interpretation of study results, including, but not limited to, active pulmonary infection, other active pulmonary lesions, or pulmonary space-occupying lesions indicated by chest X-ray (pulmonary imaging obtained within 3 months prior to screening is acceptable), chronic obstructive pulmonary disease, bronchiectasis, pulmonary fibrosis, cystic fibrosis, obesity-related hypoventilation syndrome, alpha-1 antitrypsin deficiency, and primary ciliary dyskinesia; or any pulmonary or systemic disease other than asthma associated with elevated peripheral blood eosinophil counts, such as allergic bronchopulmonary aspergillosis/mycosis, Churg-Strauss syndrome, or hypereosinophilic syndrome.
* A confirmed diagnosis of occupational asthma.
* Current smoker or a smoking history of ≥10 pack-years (pack-years = number of cigarettes smoked per day / 20 × number of years smoked). Former smokers with a smoking history of <10 pack-years must have discontinued smoking for at least 6 months before enrollment.
* An asthma exacerbation occurring within 8 weeks prior to screening through the first dose that required systemic corticosteroid treatment for ≥3 days or resulted in an emergency department visit or hospitalization for ≥24 hours.
* An upper respiratory tract infection occurring within 4 weeks prior to screening through the first dose; or a pulmonary or other infection requiring intravenous antibiotics, antifungal agents, or antiviral agents.
* A diagnosis of helminthic parasitic infection within 6 months prior to screening that has not been treated or has failed to respond to standard treatment.
* Use of another investigational drug within 5 half-lives or 30 days prior to screening, whichever is longer, or before the pharmacodynamic effect of the investigational drug has returned to baseline, whichever is longer; or a longer washout period if required for the investigational drug.
* Use of short-acting muscarinic antagonists (SAMA), such as ipratropium bromide, within 2 weeks prior to screening.
* Use of traditional Chinese medicines with antiasthmatic effects within 2 weeks prior to screening.
* Use of pranlukast within 4 weeks prior to screening.
* Receipt of a biologic agent with the same therapeutic purpose within 4 months or 5 half-lives prior to randomization, whichever is longer, including anti-thymic stromal lymphopoietin (TSLP) monoclonal antibodies, anti-IL-4Rα monoclonal antibodies, anti-IL-5/IL-5R monoclonal antibodies, anti-IgE monoclonal antibodies, or other biologics with the same therapeutic purpose.
* Receipt of allergen-specific immunotherapy within 3 months prior to randomization.
* A history of bronchial thermoplasty.
* Use of systemic immunosuppressive/immunomodulatory agents or biologic agents for the treatment of other autoimmune or inflammatory diseases within 8 weeks or 5 half-lives prior to randomization, whichever is longer, or ongoing treatment with such agents.
* Receipt of immunoglobulins or other blood products within 3 months prior to screening.
* Laboratory abnormalities meeting any of the following criteria:

  1. Hematology: hemoglobin <90 g/L, white blood cell (WBC) count <3.0 × 10⁹/L, platelet count <100 × 10⁹/L, or absolute neutrophil count (ANC) <1.5 × 10⁹/L;
  2. Blood chemistry: total bilirubin >1.5 × ULN, alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2 × ULN, or serum creatinine >1.5 × ULN.
* Any disease or medical condition that, in the investigator's judgment, is not clinically stable, including, but not limited to, unstable cardiovascular, gastrointestinal, hepatic, renal, neurological, musculoskeletal, infectious, endocrine, metabolic, hematological, or psychiatric diseases, or major physical injuries.
* A history of organ, hematopoietic stem cell, or bone marrow transplantation.
* Receipt of a live or live-attenuated vaccine within 30 days prior to screening, or plans to receive a live or live-attenuated vaccine during the study.
* A history of malignancy in any organ system within the past 5 years, except for adequately treated localized basal cell carcinoma of the skin or carcinoma in situ of the cervix, regardless of whether there is evidence of local recurrence or metastasis.
* A history of immediate hypersensitivity reactions following previous treatment with any biologic agent, or a documented diagnosis of immune complex disease (Type III hypersensitivity reaction).
* Positive human immunodeficiency virus (HIV) antibody; positive hepatitis B surface antigen (HBsAg), or positive hepatitis B core antibody (HBcAb) with positive HBV DNA; positive hepatitis C virus (HCV) antibody; or positive syphilis antibody test.
* A history of tuberculosis, or a positive interferon-gamma release assay (IGRA) at screening. An IGRA result obtained within 3 months prior to screening is acceptable.
* A history of chronic alcohol abuse or drug abuse within 12 months prior to randomization.
* Known hypersensitivity to EB070 or any of its excipients, including histidine, histidine hydrochloride, sorbitol, or polysorbate 80.
* Known history of poor adherence to medication or study procedures, inability or unwillingness to complete the study questionnaires, or inability to perform pulmonary function tests correctly.
* Pregnancy, breastfeeding, plans to become pregnant, or unwillingness to use reliable contraception during the study and for 3 months after the last dose in women of childbearing potential or sexually active men. Participants who donate sperm during the same period are also excluded.
* Any other condition that, in the investigator's opinion, makes the participant unsuitable for participation in the study, including major surgery, significant medical conditions, psychiatric disorders, or other relevant conditions.