Phase 2 Randomized, Double-Blind, Placebo-Controlled Study of Anti-TSLP Antibody GSK5784283 in Adults with Uncontrolled Asthma

Trial ID: 2024-518321-15-00
Protocol: 223125
Sponsor: Glaxosmithkline Research & Development Limited

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Diseases & Conditions

Asthma

Objectives

The primary objective of this multicenter, randomized, double-blind, placebo-controlled, dose-finding, parallel-group, Phase 2 study is to evaluate the effects of three dose levels of the anti-TSLP antibody **GSK5784283** compared to placebo on the fraction of exhaled nitric oxide (FeNO) in adults aged 18 to 75 years with uncontrolled asthma. This is clinically relevant as FeNO is a biomarker for airway inflammation, and its reduction could indicate improved asthma control.

Secondary objectives include:

Evaluating the effect of single doses of GSK5784283 compared to placebo on blood eosinophil counts, clinic visit spirometry, and patient-reported asthma control.
Assessing the effect of single doses on FeNO, blood eosinophil count, forced expiratory volume in one second (FEV1), and the Asthma Control Questionnaire 5 (ACQ-5) during the treatment period.
Characterizing the pharmacokinetics of GSK5784283 across the dose range.
Evaluating the maintenance of effect after repeat dosing on FeNO, blood eosinophil counts, lung function, and patient-reported asthma control.

Participants

The clinical trial involves a total of **157 participants** diagnosed with **asthma**. The study population includes both male and female subjects, aged between 18 to 75 years. Participants were selected based on their ability to provide informed consent and their compliance with trial procedures. The trial does not include a vulnerable population. Participants are required to have a documented history of asthma for at least two years, with evidence of variable airflow obstruction consistent with asthma. They must have a history of asthma exacerbations within the past year and a well-documented requirement for regular treatment with medium or high-dose inhaled corticosteroids for at least six months prior to screening. Additionally, participants must be on at least one other maintenance asthma controller medication. Lifestyle considerations such as diet and physical activity are not specified, but participants must weigh at least 40 kg. Female participants must not be pregnant or breastfeeding and must adhere to highly effective contraceptive methods if of childbearing potential. The trial aims to evaluate the effects of three dose levels of GSK5784283 compared to placebo on the fraction of exhaled nitric oxide (FeNO).

Plans and Procedures

The clinical trial is a **randomized**, **double-blind**, **placebo-controlled** study designed to evaluate the effects of three dose levels of the investigational drug GSK5784283 compared to placebo in adults aged 18 to 75 years with **uncontrolled asthma**. The trial is structured as a Phase 2 study with a parallel group design, aiming to assess the primary endpoint of changes in the fraction of exhaled nitric oxide (FeNO) over a 26-week period. Secondary endpoints include blood eosinophil counts, lung function, and asthma control as measured by the Asthma Control Questionnaire (ACQ-5), among others. The investigational product, GSK5784283, is administered as a **solution for injection** via **subcutaneous use**.

The trial is expected to commence recruitment on March 17, 2025, and conclude by September 14, 2027. Participants will be involved in the study for a maximum treatment period of 52 weeks. The study visits are sequenced as follows: an initial screening visit to confirm eligibility based on inclusion criteria such as documented physician-diagnosed asthma and evidence of variable airflow obstruction. This is followed by a randomization visit where eligible participants are assigned to either the investigational drug or placebo group. Subsequent follow-up visits will occur at regular intervals to monitor safety, efficacy, and adherence to the study protocol. The end-of-study visit will mark the completion of the participant's involvement, where final assessments will be conducted.

Participants may be withdrawn from the study early if they experience significant adverse events, fail to comply with the study protocol, or if the investigator deems it necessary for their safety. The trial's design ensures rigorous monitoring and data collection to achieve its objectives while maintaining participant safety and data integrity.

Treatment

The clinical trial involves the administration of **GSK5784283**, an experimental medication formulated as a **solution for injection**. This investigational drug is a biological product developed by GlaxoSmithKline Research & Development Limited. The active substance, GSK5784283, is a protein of other origin, and it is also known by the synonyms AIO-001, SHR-1905, and HRP01767. The medication is administered via **subcutaneous use**. The trial is designed to evaluate the effects of three different dose levels of GSK5784283, with the maximum treatment period extending up to 52 weeks. The dosing schedule and specific dosage amounts are determined based on the study protocol, and participant compliance is monitored throughout the trial.

The study also includes a **placebo** control, which is used to compare the effects of GSK5784283. The placebo is specifically formulated to match the experimental medication in appearance and administration route, ensuring the study remains double-blind. The placebo is administered in the same manner as GSK5784283, via subcutaneous injection, and follows the same dosing schedule. This allows for an accurate assessment of the investigational drug's efficacy and safety compared to the placebo. Compliance with the administration of the placebo is similarly monitored to maintain the integrity of the trial results.

Efficacy

The efficacy of the investigational drug GSK5784283 in the treatment of uncontrolled asthma will be assessed through a series of primary and secondary endpoints. The primary endpoint is the measurement of the fraction of exhaled nitric oxide (FeNO) in parts per billion (ppb) over a period of 26 weeks. This parameter is a recognized biomarker for airway inflammation in asthma.

Secondary endpoints include several additional measures to evaluate the drug's efficacy. These include blood eosinophil counts, lung function as measured by pre-and post-bronchodilator forced expiratory volume (FEV1) and forced vital capacity (FVC), and scores from the Asthma Control Questionnaire (ACQ-5), all assessed over 26 weeks. Furthermore, pharmacokinetic parameters of GSK5784283, such as maximum concentration (Cmax), time to reach Cmax (tmax), and area under the curve (AUC0-tau) at Week 26, will be evaluated.

In the extension phase of the study, changes from baseline in FeNO, blood eosinophil counts, lung function, and ACQ-5 scores will be assessed at Week 52 and other pre-specified timepoints. The ratio to baseline in FeNO and blood eosinophil counts will also be evaluated at these timepoints. These assessments will be conducted using validated scales and laboratory tests to ensure accuracy and reliability of the data collected.

Inclusion and Exclusion Criteria

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Inclusion Criteria

Informed Consent: Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and this protocol. The participant must be willing and able to comply with trial and follow-up procedures
Age: Participants must be 18 to 75 years of age inclusive, at the time of signing the informed consent.
Documented physician-diagnosed asthma for ≥2 years that meets the National Heart, Lung, and Blood Institute guidelines or GINA Main Report 2024 Global Strategy for Asthma Management and Prevention
Evidence of variable airflow obstruction consistent with asthma as documented by: a) Positive bronchodilator response (reversibility) during screening at either Visit 2a or Visit 2b using the Maximum Post-Bronchodilator Procedure as evidenced by an increase in FEV1 of 12% and 200 mL from the pre-bronchodilator value or b) A documented positive post-bronchodilator response (reversibility) according to the FEV1 criteria in ‘a’ (above) within 24 months of Visit 1 or c) Documented Airway hyperresponsiveness (methacholine: PC20 of <8 mg/mL, mannitol: decrease in FEV1 ≥15%) documented in the 24 months prior to Visit 3 (randomization visit). The results from consensual, alternative methods to diagnose AHR may be acceptable, as approved by the Sponsor.
Documented history of asthma exacerbations within 12 months prior to Visit 1: An asthma exacerbation is defined as a worsening of asthma symptoms that led to either of the following: the use of systemic glucocorticoids for 3 or more days (a single depo-injectable dose of corticosteroids will be considered equivalent to a 3-day course of systemic corticosteroids) or an emergency room (ER) visit (defined as evaluation and treatment for <24 hours in an ER or urgent care center) that required systemic corticosteroids (as per above) OR an inpatient hospitalization (≥24 hours) due to asthma
A well- documented requirement for regular treatment with medium or high-dose ICS for at least 6 months prior to screening. a. High-dose ICS is defined as a total daily dose (sum of all inhaled glucocorticoid) of >500μg fluticasone propionate DPI or MDI, or equivalent. b. Medium Dose ICS is defined as a total daily dose (sum of all inhaled glucocorticoid) of 250 to 500μg fluticasone propionate DPI or MDI or equivalent.
At least one additional maintenance asthma controller medication is required according to standard practice of care (e.g., LABA, LTRA, theophylline, LAMA, chromones, etc.). Use of additional asthma controller medications must be documented for at least 3 months prior to Visit 1.
Weight ≥40 kg
Male or eligible female: A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies: − Not a woman of childbearing potential (WONCBP) OR Is a WOCBP and using a contraceptive method that is highly effective, with a failure rate of <1%, 28 days prior to the 1st dose of the study drug and during the study intervention period and follow-up period after the last dose of study intervention. The investigator should evaluate potential for contraceptive method failure (e.g. non-compliance, recently initiated) in relationship to the first dose of study intervention. − A WOCBP must have a negative serum pregnancy test at screening and a highly sensitive pregnancy test ([urine or serum] as required by local regulations) within 24 hours before each dose of study intervention. o 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 location regulations regarding the methods of highly effective contraception for those participating in clinical trials. NB: Contraception for male participants with female partners of childbearing potential is not required.
Acceptable inhaler, and spirometry techniques during the run-in period.

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Exclusion Criteria

Any concomitant respiratory disease that in the opinion of the investigator and/or medical monitor will interfere with the evaluation of the investigational product or interpretation of subject safety or study results (e.g., current upper or lower respiratory tract infection, chronic obstructive pulmonary disease, cystic fibrosis, pulmonary fibrosis, bronchiectasis, allergic bronchopulmonary aspergillosis, Churg- Strauss syndrome, primary ciliary dyskinesia).
Helminth parasitic infection diagnosed within 6 months prior to Visit 1 that has not been treated with, or has failed to respond to, standard of care therapy.
Active or latent tuberculosis: − Participants with a diagnosis or evidence of active or latent tuberculosis are excluded from the study. Note: If clinically indicated, additional testing for tuberculosis should be performed by the investigator during the screening/run-in period and ahead of the randomization visit. The choice to perform a QuantiFERON Gold Plus test or T-SPOT will be made by the investigator according to local licensing and standard of care. The QuantiFERON Gold Plus test can only be used in countries where it is licensed, and the use of this test is dependent on previous treatment(s). This test may not be suitable if previous treatment(s) produced significant immunosuppression.
Diagnosis of vocal cord dysfunction, dysfunctional breathing, or pseudo steroid resistant asthma.
Malignancy: A current malignancy or previous history of cancer in remission for less than 5 years prior to screening (Participants that had localized carcinoma of the skin which was resected for cure will not be excluded).
History of an unresolved clinically significant infection within 30 days prior to Visit 1.
A known immunodeficiency (e.g. human immunodeficiency virus – HIV), other than that explained by the use of corticosteroids taken as therapy for asthma.
Participants who have known, pre-existing, clinically significant cardiac, endocrine, autoimmune, rheumatologic, metabolic, neurological, renal, gastrointestinal, hepatic, hematological or any other system abnormalities that are uncontrolled with standard treatment including eosinophilic conditions such as hyper-eosinophilic syndrome (HES) and eosinophilic granulomatosis with polyangiitis (EGPA).
Any clinically relevant abnormal findings in physical examination, hematology, clinical chemistry, urinalysis, vital signs at Visit 2 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 participate in the study.
Subjects randomized in the current study or previous studies.
Receipt of any marketed or investigational biologic agent within 4 months or 5 halflives prior to Visit 1, whichever is longer and up until the end of study.
Receipt of any investigational non-biologic agent within 30 days or 5 half-lives prior to screening, whichever is longer and up until the end of study.
Experimental vaccines are not permitted within 30 days prior to randomization and up until the end of the study.
Use of immunosuppressive medication (e.g., methotrexate, troleandomycin, oral gold, cyclosporine, azathioprine, intramuscular long-acting depot corticosteroid, maintenance systemic (oral) corticosteroids) within 3 months prior to Visit 1 and up until the end of study.
Systemic corticosteroid burst including taper within 15 days prior to Visit 1 or during the screening/run-in period. NB: Patients receiving systemic corticosteroid burst for asthma exacerbations within 15 days prior to Visit 1 should have screening visit delayed until their asthma is stable.
Subjects who have not responded to Tezepelumab treatment.
Receipt of live or live attenuated vaccine(s) within 30 days prior to randomization or plans to receive such vaccines up until the end of study.

Trial Status by Country

Country	Status	Start of Recruitment	Planned Patients
Bulgaria	Not Recruiting	17 Mar 2025	51
Czechia	Not Recruiting	17 Mar 2025	18
Germany	Not Recruiting	17 Mar 2025	14
Romania	Not Recruiting	17 Mar 2025	20
Spain	Not Recruiting	17 Mar 2025	33