A Study to Investigate the Efficacy and Safety of GSK5784283 Compared With Placebo in Participants With Uncontrolled Asthma (PERSIST ASTHMA-1)

Inclusion criteria

• Participants capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in Informed consent form (ICF). For participants aged 12 to 17 years, signed assent must be obtained from the participant in addition to signed consent from their Legally acceptable representative (LAR).
• Participants aged 12 to 80 years at the time of signing the informed consent.
• Male or eligible female participants:

• Female participants:

• A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least 1 of the following conditions applies:

i. Is a Participant of non-childbearing potential (PONCBP) or ii. Is a Participant of childbearing potential (POCBP) and using a contraceptive method that is highly effective, with a failure rate of less than (<) 1 percent (%), 28 days prior to the first dose of the study drug, and during the study intervention period and follow-up period for at least 60 weeks 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 POCBP 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.
• 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.
• A documented physician diagnosis of asthma for at least 12 months prior to Visit 1, according to the Global Initiative for Asthma (GINA) 2026 guidelines.
• Evidence of variable airflow obstruction consistent with asthma.
• Documented history of asthma exacerbation within 12 months prior to Visit 1.
• A well-documented requirement for regular treatment with medium or high dose Inhaled corticosteroid (ICS) for at least 3 months prior to screening with or without maintenance oral corticosteroids (OCS).
• At least 1 additional maintenance asthma controller medication is required according to standard practice of care (e.g., Long-acting beta-2 agonist [LABA], Leukotriene receptor antagonists [LTRA], theophylline, Long-acting muscarinic agonists [LAMA], chromones, etc.). Use of additional asthma controller medications must be documented for at least 3 months prior to screening.
• Uncontrolled asthma based on ACQ-5 score.

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 participant safety or study results.
• History of malignant neoplasm within the last 5 years (except definitively treated non-melanoma skin cancer or carcinoma in situ of the uterine cervix).
• Myocardial infarction, unstable angina or stroke within 6 months of screening, unstable arrhythmia.
• New York Heart Association (NYHA) class III or IV heart failure.
• Other significant medical conditions that could impact participants' safety or study outcomes.
• History of an unresolved clinically significant infection within 30 days prior to Visit 1.
• A known immunodeficiency, other than that explained by the use of corticosteroids taken as therapy for asthma.
• Receipt of any marketed or investigational biologic agent or investigational non-biologic agent, prior to Visit 1.
• Use of systemic immunosuppressive medication within 3 months prior to Visit 1 (other than systemic corticosteroid burst or stable maintenance OCS for treatment of asthma).
• Current smokers (tobacco and/or marijuana), current users of vaping products/electronic-cigarettes or participants with a smoking history >=10 pack-years.