A dose finding study with an anti-TSLP antibody (GSK5784283) in adults aged 18 to 75 years of age with uncontrolled asthma.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Glaxosmithkline Research & Development Limited

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

Trial duration

30 May 2025 → ongoing

Decision date (initial)

2025-05-02

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

GlaxoSmithKline Research & Development Limited

External identifiers

EU CT number

2024-518321-15-00

ClinicalTrials.gov

NCT06748053

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Others, Safety

To evaluate the effect of single doses of GSK5784283 compared to placebo on fraction of exhaled nitric oxide (FeNO).

Secondary objectives 6

1. Part A Dose Finding: To evaluate the effect of single doses of GSK5784283 compared to placebo on blood eosinophil counts
2. Part A Dose Finding: To evaluate the effect of single doses of GSK5784283 compared to placebo on clinic visit spirometry
3. Part A Dose Finding: To assess the effect of single doses of GSK5784283 compared to placebo on patient reported asthma control
4. Part A Dose Finding: To evaluate the effect of single doses of GSK5784283 on FeNO, blood eosinophil count, FEV1 and ACQ-5 during the treatment period
5. Part A Dose Finding: To characterize the pharmacokinetics (PK) of GSK5784283 across the dose range
6. Part B Extension: To evaluate the maintenance of effect after repeat dosing of GSK5784283 on FeNO, blood eosinophil counts, lung function and patient reported asthma control

Conditions and MedDRA coding

Asthma

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration, European Medicines Agency

Plan to share IPD

Yes

IPD plan description

Individual treatment assignments and data will be shared, upon request, after the study is complete.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. 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
2. Age: Participants must be 18 to 75 years of age inclusive, at the time of signing the informed consent.
3. 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
4. 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.
5. 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
6. 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.
7. 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.
8. Weight ≥40 kg
9. 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.
10. Acceptable inhaler, and spirometry techniques during the run-in period.

Exclusion criteria 17

1. 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).
2. 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.
3. 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.
4. Diagnosis of vocal cord dysfunction, dysfunctional breathing, or pseudo steroid resistant asthma.
5. 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).
6. History of an unresolved clinically significant infection within 30 days prior to Visit 1.
7. A known immunodeficiency (e.g. human immunodeficiency virus – HIV), other than that explained by the use of corticosteroids taken as therapy for asthma.
8. 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).
9. 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.
10. Subjects randomized in the current study or previous studies.
11. 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.
12. 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.
13. Experimental vaccines are not permitted within 30 days prior to randomization and up until the end of the study.
14. 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.
15. 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.
16. Subjects who have not responded to Tezepelumab treatment.
17. 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. FeNO (ppb) over 26 Weeks.

Secondary endpoints 9

1. Part A Dose Finding: Blood eosinophil counts over 26 Weeks.
2. Part A Dose Finding: Lung function as measured by pre-and postbronchodilator forced expiratory volume (FEV1) and forced vital capacity (FVC) over 26 Weeks.
3. Part A Dose Finding: Asthma Control Questionnaire (ACQ-5) over 26 Weeks.
4. Part A Dose Finding: Maximum change from baseline in FeNO, blood eosinophil count, FEV1 and ACQ-5 over 26 Weeks
5. 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
6. Part B Extension: Change from baseline in FeNO and blood eosinophil counts at Week 52 and other prespecified timepoints according to SoA
7. 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
8. Part B Extension: Change from baseline in ACQ-5 at Week 52 and other pre-specified timepoints according to the SoA
9. Part B Extension: Ratio to baseline in FeNO and blood eosinophil counts at Week 52 and other pre-specified timepoints according to SoA

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Glaxosmithkline Research & Development Limited

Sponsor organisation

Glaxosmithkline Research & Development Limited

Address

79 New Oxford Street

City

London

Postcode

WC1A 1DG

Country

United Kingdom

Scientific contact point

Organisation

Glaxosmithkline Research & Development Limited

Contact name

EU GSK Clinical Trials Call Center

Public contact point

Organisation

Glaxosmithkline Research & Development Limited

Contact name

EU GSK Clinical Trials Call Center

Third parties 10

Locations

5 EU/EEA countries · 60 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 143 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications