Phase 2 Randomized, Double-Blind, Placebo-Controlled Study of WIN378 (Human IgG1 Monoclonal Antibody Against TSLP) in Adults with Moderate to Severe Asthma

Trial ID: 2025-521391-58-00
Protocol: WB-2101
Sponsor: Windward Bio AG

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Diseases & Conditions

Asthma

Objectives

The primary objective of this study is to evaluate the safety and tolerability of WIN378 in adults with asthma. Additionally, the study aims to describe the pharmacokinetics and immunogenicity of the investigational product.

Secondary objectives include:

Evaluation of the dose-response of WIN378 on fractional exhaled nitric oxide (FeNO) at 24 weeks.
Assessment of the effect of three dose levels on forced expiratory volume in 1 second (FEV1) and overall lung function at 24 and 48 weeks.
Measurement of the effect of three dose levels on FeNO levels at 24 and 48 weeks.
Evaluation of the impact on blood eosinophil counts (BEC) at 24 and 48 weeks.
Characterization of the exposure-response relationship to inform future dose selection.
Assessment of the effect on asthma symptoms and metrics related to asthma control.

Participants

The study includes 58 participants consisting of males and females between the ages of 18 and 75 years. The study population is composed of patients with asthma characterized by a T2-high phenotype, defined by elevated peripheral blood eosinophil counts or a documented history of high eosinophil levels. Eligible individuals must exhibit airflow limitation and meeting specific asthma control thresholds using the ACQ-6 score. Participants are required to be on a stable maintenance regimen involving inhaled corticosteroids and at least one additional controller medication. Further requirements include a history of at least one asthma exacerbation within the previous 12 months, a body mass index between 18 and 40 kg/m2, and a fractional exhaled nitric oxide level of ≥25 ppb. The study objectives are:

To evaluate the safety and tolerability of WIN378.
To describe the pharmacokinetics and immunogenicity of WIN378.

Plans and Procedures

This Phase 2, randomized, double-blind, placebo-controlled study is designed to evaluate the pharmacokinetics, immunogenicity, safety, and efficacy of WIN378, a human IgG1 monoclonal antibody against TSLP, in adults with moderate or severe asthma. Participants will receive either a 300 mg subcutaneous injection of the test product or a matching placebo. The study includes a screening period and a run-in phase to assess FEV1 reversibility, blood eosinophil count, and medication compliance. Following the initial visits, the intervention period extends through Week 48, with safety monitoring continuing through a follow-up period at Week 60. Primary assessments focus on treatment-emergent adverse events, vital signs, electrocardiogram, and anti-drug antibodies. Secondary endpoints include changes in fractional exhaled nitric oxide, lung function, and asthma exacerbation rates. Total participant involvement is expected to last approximately 60 weeks.

Treatment

WIN378 is a human IgG1 monoclonal antibody targeting thymic stromal lymphopoietin (TSLP). This investigational product is administered as a 300 mg injection via the subcutaneous route.

A matching placebo is utilized for comparison during the study.

Efficacy

Efficacy assessment in this study of asthma involves several parameters. The change from baseline in fractional exhaled nitric oxide (FeNO) is evaluated at Week 24 and Week 48. Forced expiratory volume in one second (FEV1) and blood eosinophil count (BEC) are measured at Week 24 and Week 48. Lung function is further assessed through pre-bronchodilator (pre-BD) and post-bronchodilator (post-BD) FEV1 and forced vital capacity (FVC) at Week 24 and Week 48.

Secondary efficacy measures include:

Changes in asthma symptoms and control at Week 48, utilizing the Asthma Symptom Diary and the Asthma Control Questionnaire (ACQ-6).
The annualized asthma exacerbation rate (AAER), rate of severe exacerbations, time to first exacerbation, and the proportion of participants experiencing exacerbations over 48 weeks.
Changes in quality of life at Week 48 as measured by the Asthma Quality of Life Questionnaire (AQLQ[S]+12) and the European Quality of Life - 5 Dimensions 5 Level Version (EQ-5D-5L).

An exposure-response analysis is conducted to evaluate the relationship between WIN378 concentration and changes in FeNO, FEV1, and eosinophil count over 48 weeks.

Inclusion and Exclusion Criteria

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Inclusion Criteria

Age 18 through 75, inclusive at the time of signing the informed consent
Documented physician-diagnosed asthma for at least 12 months prior to Visit 1 and evidence of variable airflow obstruction consistent with asthma as documented by: 1. Post-BD reversibility of FEV1 ≥12% and ≥200 mL during Screening OR 2. Documented history of post-BD FEV1 reversibility in the past 24 months OR 3. Positive methacholine challenge in the past 24 months OR 4. Confirmed evidence of variable expiratory airflow consistent with asthma as documented by other means according to GINA[1] Main Report, 2025, Box 1-2 within 24 months before Visit 1 or during the Screening Run-in, see Appendix 11. NOTE: post-BD FEV1 can be re-tested once during Screening Run-in.
Participants must have an ACQ-6 score of ≥1.5 and at Week 0 (Visit 4 in Part A and Visit 2 in Part B). (Week 0).
Males or eligible females. A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least 1 of the following conditions applies: 1. Is not a woman of childbearing potential (WOCBP) as defined in Appendix 4 OR 2. Is a WOCBP and using a contraceptive method that is highly effective, with a failure rate of <1%, 28 days prior to the first dose of the trial drug and during the trial treatment period until at least 36 weeks after the last administered dose. A WOCBP must have a negative serum pregnancy test at Visit 1 and a highly sensitive pregnancy test (urine or serum per local requirement) within 24 hours before each dose of trial drug. If a urine test cannot be confirmed as negative (e.g., an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive. The Investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy. Contraceptive use by women should be consistent with local regulations regarding the methods of highly effective contraception for those participating in clinical trials.
Male participants should not donate nor cryopreserve sperm, and female participants should not donate nor cryopreserve ova for the duration of the trial from Visit 1 until the end of the Safety Follow-up period.
Body mass index between 18 and 40 kg/m2 inclusive, and weight ≥40 kg at Visit 1.
Written informed consent and any locally required authorization obtained from the participant prior to performing any protocol-related procedures.
Additional Criteria for Part A Only: Elevated peripheral BEC of ≥150 cells/µL related to asthma during Screening. If eosinophils are <150 cells/µL, 1 retest to confirm eligibility during the Screening or Run-in period will be accepted. OR Documented history of BEC ≥300 cells/µL related to asthma in prior 12 months.
Additional Criteria for Part A Only: Airflow limitation during Screening as indicated by pre-BD FEV1 value of ≥30% and ≤90%, predicted NOTE: pre-BD FEV1 can be re-tested once during Screening Run-in period.
Additional Criteria for Part A Only: Participants must have received a physician-prescribed asthma controller maintenance regimen with low-, medium-, or high-dose ICS (GINA steps 3 to 5). At least 1 additional maintenance asthma controller medication is required, according to standard of care (e.g., LABA, leukotriene modifier, 5‑Lipoxygenase inhibitors, theophylline, LAMA, chromones and/or OCS). Inhaled corticosteroids can be contained within an ICS/LABA combination product. (EU-specific): In the EU, participants must be on high-dose ICS. The use of ICS plus at least 1 additional asthma controller medication must be documented for at least 3 months prior to Visit 1. Patients with mild asthma (GINA step 1 to 2) are not eligible. If on allergen-specific immunotherapy, participants must be on a stable maintenance dose and schedule for at least 2 months prior to Visit 1.
Additional Criteria for Part A Only: FeNO of ≥25 ppb at randomization.
Additional Criteria for Part A Only (EU-Specific): In the EU, participants must have a history of at least 1 asthma exacerbation in the 12 months prior to Visit 1. An asthma exacerbation is defined as a worsening of asthma symptoms that leads to either of the following: the use of systemic corticosteroids or increase in maintenance dose of OCS for at least 3 days (a single depot-injectable dose of corticosteroids will be considered equivalent to a 3-day course of systemic corticosteroids), or an emergency room (ER) or urgent care facility visit due to asthma, or an in-patient hospitalization due to asthma.
Additional Criteria for Part B Only : Airflow limitation during Screening as indicated by pre-BD FEV1 value of ≥30% and ≤80%, predicted. Note: pre-BD FEV1 can be re-tested once during Screening Run-in. For participants who are re-screened, the pre-BD FEV1 value from the first screening attempt can be used in case there were no changes to the asthma background medications and value was assessed within 3 months before re-screening.
Additional Criteria for Part B Only: Participants must have received a physician-prescribed asthma controller maintenance regimen with medium- or high-dose ICS (GINA step 4 to 5). At least one additional maintenance asthma controller medication is required according to standard practice of care (e.g., LABA, leukotriene modifier, 5-Lipoxygenase inhibitors), theophylline, LAMA, chromones and/or OCS. Inhaled corticosteroids can be contained within an ICS/LABA combination product. Use of medium-/high-dose ICS plus at least 1 additional asthma controller medication must be documented for at least 3 months prior to Visit 1 and be stable for at least 1 month prior to Visit 1. If on allergen-specific immunotherapy, participants must be on a stable maintenance dose and schedule for at least 2 months prior to Visit 1.
Additional Criteria for Part B Only: Participants must have a documented history of at least 2 asthma exacerbation events within 12 months before Visit 1. Refer to Section 8.1.6 for information regarding acceptable documentation for historical exacerbations. An asthma exacerbation is defined as a worsening of asthma that requires either of the following: - treatment with systemic corticosteroids or increase in maintenance dose of OCS for at least 3 consecutive days (a single depot-injectable dose of corticosteroids will be considered equivalent to a 3-day course of systemic corticosteroids), or - an ER or urgent care facility visit due to asthma, or - an in-patient hospitalization due to asthma (defined as admission to an in-patient facility and/or evaluation and treatment in a healthcare facility for ≥24 hours).
Participants must meet all of the following criteria at Week 0, Day 1 (Visit 4 in Part A and Visit 2 in Part B) prior to randomization: - Participants must demonstrate acceptable inhaler, peak flow meter, and spirometry techniques during the Screening Run-in period. - Participants must demonstrate ≥70% compliance with usual asthma controller medications during the Screening Run-in period based on the eDiary. - Participants must demonstrate ≥70% compliance with required use of the electronic patient-reported outcome (ePRO) device; for Part A, 70% compliance is defined as completing the Asthma Daytime Symptom (eDiary) for any 7 mornings and any 7 evenings in the last 10 days of the Screening Run-in period.

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Exclusion Criteria

Participants with a known, pre-existing, clinically important lung condition other than asthma. This includes (but is not limited to) current acute or latent viral or bacterial infection (including COVID-19), diagnosis of vocal cord dysfunction, reactive airways dysfunction syndrome, hyperventilation and panic attacks, or other mimics of asthma. An established diagnosis of occupational asthma, chronic obstructive pulmonary disease, cystic fibrosis, pulmonary fibrosis, bronchiectasis, or allergic bronchopulmonary aspergillosis.
Start of leukotriene modifying agents (e.g., montelukast, zileuton), less than 3 months prior to Visit 1, non-selective β-adrenergic antagonists (e.g., propranolol), or recent oral corticosteroid burst (including taper) within 30 days prior to Visit 1 or during the Screening Run-in period.
Current smokers (tobacco and marijuana), former smokers who quit smoking within less than 6 months before Visit 1 or former smokers with a smoking history ≥10 pack years and participants using vaping products, including electronic cigarettes.
Acute upper or lower respiratory infections requiring antibiotics or antiviral medications within 28 days prior to Visit 1. Any acute viral or bacterial upper or lower respiratory infection during Screening R
History of chronic alcohol or drug abuse within 24 months prior to Visit 1.
20.History of chronic alcohol or drug abuse within 24 months prior to Visit 1.
Participants who are pregnant, lactating or breastfeeding. Participants should not be enrolled if they plan to become pregnant during the time of trial participation. Participants should not plan to donate or cryopreserve sperm or ova during the trial, from Visit 1 until the end of the Safety Follow-up period
Participants who have known evidence of lack of adherence to controller medications, inability to follow physician’s recommendations or unwillingness or inability to follow trial procedures and instructions through until the end of the Safety Follow-Up period.
Planned surgical procedures requiring general anesthesia or in-patient stay for >1 day during the conduct of the trial.
3.Participants with other conditions that could lead to elevated eosinophils such as hyper-eosinophilic syndromes including (but not limited to) Eosinophilic Granulomatosis with Polyangiitis (EGPA, formerly known as Churg-Strauss Syndrome) or Eosinophilic Esophagitis.
Participants with a helminth parasitic infection diagnosed within 24 weeks of Visit 1 that has not been treated or has not responded to standard of care therapy.
Evidence of a clinically significant non-respiratory infection or receiving treatment with antibiotics or antiviral medications at (Week 0, Day 1).
Participants with untreated active or latent tuberculosis (TB) or who have required treatment for TB within the 12 months prior to Visit 1. NOTE: If clinically indicated, additional testing for TB should be performed by the Investigator during the Screening Run-in period and ahead of the randomization visit. The choice to perform a screening test e.g., QuantiFERON Gold Plus test is per Investigator’s judgment according to local licensing and standard of care.
A known primary or acquired immunodeficiency (e.g., HIV) other than that explained by the use of corticosteroids taken as therapy for asthma. Asymptomatic selective immunoglobulin A or immunoglobin G subclass deficiency is permitted.
Cirrhosis or current unstable liver or biliary disease per Investigator’s assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice or known hepatic or biliary abnormalities. NOTE: Stable non-cirrhotic chronic liver disease due to Gilbert syndrome or asymptomatic gallstones are acceptable if the participant otherwise meets entry criteria.
History of cancer except those with curative treatment completed at least 5 years before Visit 1, or basal cell carcinoma provided that curative therapy was completed at least 12 months prior to Visit 1.
Concurrent enrollment in another clinical trial involving an investigational interventional treatment. For Part B: Previous participation in Part A with WIN378 excludes participation in Part B.
Any clinically relevant abnormal findings in hematology, clinical chemistry, or urinalysis (laboratory results from Visit 1), which in the opinion of the Investigator, may put the participant at risk because of his/her participation in the trial, or may influence the results of the trial, or the participant’s ability to participate in the trial.
Liver Chemistry (laboratory results from Visit 1) - Alanine aminotransferase (ALT) >2x upper limit of normal (ULN) - Total bilirubin >1.5x ULN (isolated bilirubin up to 3x ULN is acceptable if bilirubin is fractionated and direct bilirubin ≤1.0 ULN in the presence of concomitant Gilbert syndrome). NOTE: borderline results can be re-tested once during Screening or Run-in.
Clinically significant abnormality on ECG that would impact the participant’s safety or participation during the trial, based on evaluation of the Investigator.
Viral Serology at Visit 1: - Positive Hepatitis B surface antigen - Positive Hepatitis B core antibody NOTE: A participant who tests positive for hepatitis core antibody can be enrolled in the trial, providing that they test negative for HBV DNA and test negative for Hepatitis B surface antigen (Section 1.3) - Positive Hepatitis B virus DNA (will only be tested in participants who test positive for Hepatitis B core antibody). - Positive Hepatitis C antibody test result. NOTE: Participants with positive Hepatitis C antibody due to prior resolved disease can be enrolled, only if a confirmatory negative Hepatitis C RNA test result is obtained. - A positive HIV test
"Recent history (i.e., 6 months or less prior to Visit 1) of myocardial infarction, arterial, or venous thromboembolism, stroke, transient ischemic event, unstable angina, any unstable or life-threatening cardiac arrhythmia requiring intervention or change in drug therapy during the 6 months prior to Visit1, or participants who have been hospitalized for cardiac failure during the past year prior to Visit 1. Known valvulopathy or pulmonary hypertension
A positive urine pregnancy test confirmed by serum pregnancy test
Part B: asthma exacerbation in the 7 requiring systemic corticosteroids within 30 days prior to Visit 1 and until randomization whereby the 30 days apply to the last dose of systemic corticosteroids to treat the asthma exacerbation (or return to maintenance dose for participants on stable OCS). NOTE: In Part A, participants should have their randomization visit delayed until ic corticosteroids (or return to maintenance dose for participants on stable OCS).
Any change in the dose or regimen of baseline ICS and/or additional controller medication during the Screening Run-in period.
Th2 cytokine inhibitor (e.g., suplatast tosilate) used within 30 days prior to Visit 1 or during Screening Run-in
Recent history (i.e., 6 months or less prior to Visit 1) of myocardial infarction, arterial, or venous thromboembolism, stroke, transient ischemic event, unstable angina, any unstable or life-threatening cardiac arrhythmia requiring intervention or change in drug therapy during the 6 months prior to Visit1, or participants who have been hospitalized for cardiac failure during the past year prior to Visit 1. Known valvulopathy or pulmonary hypertension
Other Concurrent Medical Conditions Participants who have known, pre-existing, clinically significant endocrine, autoimmune, metabolic, neurological, renal, gastrointestinal, hepatic, hematological, or any other organ or system abnormalities that are uncontrolled with standard treatment or in the opinion of the Investigator and/or medical monitor may compromise the safety of the participant in the trial or interfere with evaluation of the investigational product or reduce the participant’s ability to participate in the trial. Participants with well-controlled comorbid disease (e.g., hypertension, hyperlipidemia, gastroesophageal reflux disease) on a stable treatment regimen for 15 days prior to Visit 1 are eligible.
Participants who have received tezepelumab within 6 months of Visit 1 or who stopped tezepelumab or any other anti-thymic stromal lymphopoietin (TSLP) therapy due todue to treatment failure or due to an adverse event.
Marketed monoclonal antibodies, immunoglobulins, blood products or vaccines: • Receipt of any marketed biologic agent within 4 months or 5 half-lives prior to Visit 1, whichever is longer during Screening Run-in and throughout the trial drug treatment period. • Receipt of immunoglobulin or blood products within 30 days prior to Visit 1, during Screening Run-in and throughout the trial drug treatment period (unless there is a medical need as judged by the Investigator). • Receipt of any live or attenuated vaccines within 30 days prior to Visit 1, during Screening Run-in and until end of trial.
Use of immunosuppressive medication (e.g., methotrexate, troleandomycin, oral gold, cyclosporine, azathioprine, intramuscular (IM) long-acting depot corticosteroid, or any experimental anti-inflammatory therapy) within 3 months prior to Visit 1 or during the Screening Run-in and throughout the trial drug treatment period. Chronic oral prednisone or equivalent up to a maximum of 10 mg daily or 20 mg every other day for the maintenance treatment of asthma (or higher doses [burst] to treat asthma exacerbation if stopped >30 days before Visit 1) is permitted.
Investigational use of nonbiologic agents, biologic agents, and Vaccines • Participants who have received treatment with any investigational nonbiologic agent within 30 days or 5 half-lives prior to Visit 1, whichever is longer. • Participants who have received treatment with an investigational biologic agent within 4 months or 5 half-lives prior to Visit 1, whichever is longer. • Receipt of experimental vaccinations within 30 days prior to randomization and up until the end of the trial.
Bronchial thermoplasty within 12 months prior to Visit 1 or planned during trial period.

Trial Status by Country

Country	Status	Start of Recruitment	Planned Patients
Bulgaria	Recruiting	05 Nov 2025	55
France	Not Recruiting	05 Nov 2025	4
Germany	Recruiting	05 Nov 2025	81
Spain	Recruiting	05 Nov 2025	40
Sweden	Not Recruiting	05 Nov 2025	22