GSK5784283 for Asthma

Inclusion criteria

• {"criterion_text":"- 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"}
• {"criterion_text":"- Acceptable inhaler, and spirometry techniques during the run-in period."}
• {"criterion_text":"- Age: Participants must be 18 to 75 years of age inclusive, at the time of signing the informed consent."}
• {"criterion_text":"- 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"}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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"}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Weight ≥40 kg"}
• {"criterion_text":"- 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."}

Exclusion criteria

• {"criterion_text":"- 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)."}
• {"criterion_text":"- Subjects randomized in the current study or previous studies."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Experimental vaccines are not permitted within 30 days prior to randomization and up until the end of the study."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Subjects who have not responded to Tezepelumab treatment."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Diagnosis of vocal cord dysfunction, dysfunctional breathing, or pseudo steroid resistant asthma."}
• {"criterion_text":"- 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)."}
• {"criterion_text":"- History of an unresolved clinically significant infection within 30 days prior to Visit 1."}
• {"criterion_text":"- A known immunodeficiency (e.g. human immunodeficiency virus – HIV), other than that explained by the use of corticosteroids taken as therapy for asthma."}
• {"criterion_text":"- 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)."}
• {"criterion_text":"- 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."}

Primary endpoints

• {"endpoint_text":"- FeNO (ppb) over 26 Weeks.","definition_or_measurement_approach":"Fraction of exhaled nitric oxide (FeNO) measured in parts per billion (ppb) over a 26-week treatment period."}

Secondary endpoints

• {"endpoint_text":"- Part A Dose Finding: Blood eosinophil counts over 26 Weeks.","definition_or_measurement_approach":"Blood eosinophil counts measured over 26 weeks."}
• {"endpoint_text":"- Part A Dose Finding: Lung function as measured by pre-and postbronchodilator forced expiratory volume (FEV1) and forced vital capacity (FVC) over 26 Weeks.","definition_or_measurement_approach":"Spirometry measurements (pre- and post-bronchodilator FEV1 and FVC) collected over 26 weeks."}
• {"endpoint_text":"- Part A Dose Finding: Asthma Control Questionnaire (ACQ-5) over 26 Weeks.","definition_or_measurement_approach":"Patient-reported asthma control using the ACQ-5 instrument measured over 26 weeks."}
• {"endpoint_text":"- Part A Dose Finding: Maximum change from baseline in FeNO, blood eosinophil count, FEV1 and ACQ-5 over 26 Weeks","definition_or_measurement_approach":"Maximum change from baseline for FeNO, blood eosinophils, FEV1 and ACQ-5 assessed through Week 26."}
• {"endpoint_text":"- Part A Dose Finding: PK parameters of GSK5784283: maximum value (Cmax), time of Cmax (tmax), and area under the curve over the dosing interval (AUC0-tau) at Week 26","definition_or_measurement_approach":"Pharmacokinetic parameters (Cmax, tmax, AUC0-tau) for GSK5784283 measured at Week 26."}
• {"endpoint_text":"- Part B Extension: Change from baseline in FeNO and blood eosinophil counts at Week 52 and other prespecified timepoints according to SoA","definition_or_measurement_approach":"Change from baseline in FeNO and blood eosinophil counts measured at Week 52 and other Scheduled timepoints per the Schedule of Assessments."}
• {"endpoint_text":"- Part B Extension: Change from baseline in lung function as measured by pre- and post-bronchodilator FEV1 and FVC at Week 52 and other pre-specified timepoints according to SoA","definition_or_measurement_approach":"Change from baseline in pre- and post-bronchodilator FEV1 and FVC at Week 52 and other prespecified timepoints."}
• {"endpoint_text":"- Part B Extension: Change from baseline in ACQ-5 at Week 52 and other pre-specified timepoints according to the SoA","definition_or_measurement_approach":"Change from baseline in ACQ-5 at Week 52 and other prespecified timepoints."}
• {"endpoint_text":"- Part B Extension: Ratio to baseline in FeNO and blood eosinophil counts at Week 52 and other pre-specified timepoints according to SoA","definition_or_measurement_approach":"Ratio to baseline assessments for FeNO and blood eosinophil counts at Week 52 and other prespecified timepoints."}

Methods

• Dr-to-Patient Letter - physician-sent letters (documented in K2 recruitment materials).
• Physician Referral Letter - referral via treating physicians (K2 recruitment materials).
• Patient Brochure / About Clinical Research Studies Brochure - informational brochures for potential participants (K2 recruitment materials).
• Patient Pre-Enrollment Information Card and Patient Post-Enrollment Information Card - printed information cards for participants.
• Patient Advocacy Group Letter - outreach to patient advocacy groups (materials present though no specific group named).
• Animation Storyboard / Animation Video Storyboard - informational animation/storyboard materials for recruitment.
• Site recruitment materials and site-specific recruitment packs (K2_Site_Recruitment_Material).
• Digital eCOA and app-based materials (ZEPHYRx screenshots and participant guides) and online survey terms of use (digital engagement and remote data capture).

Czechia

Earliest CTIS Part Ii Submission Date

03-04-2025

Latest Decision Or Authorization Date

08-10-2025

Processing Time Days

188

Number Of Sites

4

Number Of Participants

18

Romania

Earliest CTIS Part Ii Submission Date

26-03-2025

Latest Decision Or Authorization Date

13-10-2025

Processing Time Days

202

Number Of Sites

8

Number Of Participants

20

Bulgaria

Earliest CTIS Part Ii Submission Date

07-04-2025

Latest Decision Or Authorization Date

13-10-2025

Processing Time Days

190

Number Of Sites

16

Number Of Participants

51

Spain

Earliest CTIS Part Ii Submission Date

27-03-2025

Latest Decision Or Authorization Date

09-10-2025

Processing Time Days

197

Number Of Sites

23

Number Of Participants

33

Germany

Earliest CTIS Part Ii Submission Date

28-03-2025

Latest Decision Or Authorization Date

10-10-2025

Processing Time Days

197

Number Of Sites

14

Number Of Participants

14

Primary sponsor

Full Name

Glaxosmithkline Research & Development Limited

Organisation Type

Pharmaceutical company

Country Of Registered Address

United Kingdom

Contract research organisations

Name

IQVIA Limited

Responsibilities

Multiple sponsor duties including operational support (sponsorDuties codes: [1,11,12,13,2,5,6,7])

Name

Evidera Inc.

Responsibilities

SPFQ questionnaire (collection/management of SPFQ)

Name

Pharmaceutical Product Development LLC

Responsibilities

Clinical operations support (sponsorDuties code: 4)

Name

PPD Global Central Labs

Responsibilities

Central laboratory services (sponsorDuties code: 4)

Name

Charles River Laboratories Inc.

Responsibilities

Sample management/processing (sponsorDuties code: 4)

Name

eResearchTechnology GmbH

Responsibilities

Collect and analyze spirometry and FeNO data

Name

Medidata Solutions Inc.

Responsibilities

Electronic data capture/eClinical systems (sponsorDuties code: 7)

Third parties

• {"country":"United Kingdom","full_name":"IQVIA Limited","duties_or_roles":"sponsorDuties codes: [1,11,12,13,2,5,6,7]","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Glaxosmithkline LLC","duties_or_roles":"sponsorDuties codes: [4]","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Evidera Inc.","duties_or_roles":"sponsorDuties: [{\"code\":15,\"value\":\"SPFQ questionnaire\"}]","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Pharmaceutical Product Development LLC","duties_or_roles":"sponsorDuties codes: [4]","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"sponsorDuties codes: [7]","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Charles River Laboratories Inc.","duties_or_roles":"sponsorDuties codes: [4]","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"eResearchTechnology GmbH","duties_or_roles":"sponsorDuties: [{\"code\":15,\"value\":\"collect and analyze the spirometry and FeNO data\"}]","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Infinity Biologix LLC","duties_or_roles":"sponsorDuties codes: [4]","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Accurant Biotech Inc.","duties_or_roles":"sponsorDuties codes: [4]","organisation_type":"Pharmaceutical company"}
• {"country":"Belgium","full_name":"PPD Global Central Labs","duties_or_roles":"sponsorDuties codes: [4]","organisation_type":"Pharmaceutical company"}