A phase 3b study of depemokimab on airway structure and function in patients with type 2 asthma utilizing quantitative high-resolution CT and a bronchoscopic airway sampling sub study

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

26 Nov 2025 → ongoing

Decision date (initial)

2025-10-20

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2024-519976-19-00

ClinicalTrials.gov

NCT06979323

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

To describe the change from baseline (Week 0) in total mucus plug volume measured at total lung capacity (TLC) at Week 26 following treatment with depemokimab.

Secondary objectives 1

1. To describe the change from baseline (Week 0) in airway wall thickness measured at TLC at Week 52 following treatment with depemokimab

Conditions and MedDRA coding

Asthma with type 2 inflammation characterized by an eosinophilic phenotype

Study design 3 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 14

1. 1. Participants must be ≥18 years of age, at the time of signing the informed consent form (ICF)
2. 2. Documented clinical diagnosis of asthma for ≥2 years as per the National Heart, Lung, and Blood Institute guidelines[NHLBI, 2020], GINA guidelines [GINA, 2024], or joint guidance from the British Thoracic Society, National Institute for Health and Care Excellence, and Scottish Intercollegiate Guidelines Network [NICE, 2024] along with the following: • An eosinophilic phenotype as evidenced by a blood eosinophil count of ≥300 cells/μL at screening or a documented history of blood eosinophil count ≥300 cells/μL within 3 months prior to screening. • Exhaled nitric oxide (FeNO) measure of ≥25ppb recorded at screening. • Previously confirmed history of ≥ 2 exacerbations requiring treatment with systemic corticosteroid (SCS; IM, IV, or oral), in the 12 months prior to screening, despite the use of medium to high dose ICS.
3. 3. Uncontrolled asthma indicated by ACQ5 > 1.5 recorded at screening.
4. 4. Persistent airflow obstruction as indicated by pre-bronchodilator FEV1 <80% predicted (GLI 2012) and recorded at screening.
5. 5. A well-documented requirement for regular treatment with medium or high dose ICS (in the 12 months prior to screening with or without maintenance OCS).
6. 6. Current treatment with at least one additional asthma controller medication, besides ICS, for at least 3 months [e.g., LABA, LAMA, leukotriene receptor antagonist (LTRA), or theophylline].
7. 7. Male or female. • Male Participants: No additional requirements for male participants.
8. 8. Female Participants: A female participant is eligible to participate if she is not pregnant or breastfeeding, and one of the following conditions applies: • Is a participant of non-childbearing potential (PONCBP) as defined in Section 10.4 (Appendix 4: Contraception and barrier guidance) OR • Is a participant of childbearing potential (POCBP) and using a contraceptive method that is highly effective (with a failure rate of <1% per year), with low user dependency, 14 days prior to and during the study intervention period and for at least 35 weeks after the last dose of study intervention. The investigator should evaluate the potential for contraceptive method failure (e.g., noncompliance, recently initiated) in relationship to the first dose of study intervention.
9. 9. A POCBP must have a negative highly sensitive pregnancy test (urine or serum as required by local regulations) within 24 hours before the first dose of study intervention (see Section 8.3.5 Pregnancy testing). • 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. • Additional requirements for pregnancy testing during and after the study intervention are located in Section 8.3.5. • The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a participant with an early undetected pregnancy. Note: If the childbearing potential changes after start of the study or the risk of pregnancy changes (e.g., a female participant who is not heterosexually active becomes active), the participant must discuss this with the investigator, who should determine if a female participant must begin a highly effective method of contraception. If reproductive status is questionable, additional evaluation should be considered. • Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.
10. 10. Participants who sign Informed Consent for biopsy sub study.
11. 11. Participants with post bronchodilator FEV1 ≥ 50% predicted
12. 12. Participants with no known increased risk for bleeding including: • No history of easy bleeding, bruising or known bleeding diathesis • No current anticoagulant and antiplatelet therapy • No acetylsalicylic acid use within 2 weeks of the planned procedure • Normal screening platelet count
13. 13. Participants with no specific contraindication to bronchoscopy with endobronchial biopsy in the opinion of the investigator.
14. 14. No history of allergic reaction to local anesthesia or general anesthetic agent, which ever relevant to the procedure being performed.

Exclusion criteria 20

1. 1. Presence of a known pre-existing, clinically important lung condition other than asthma. This includes (but is not limited to) current infection, bronchiectasis, pulmonary fibrosis, bronchopulmonary aspergillosis, or a history of lung cancer. Participants with current diagnoses of emphysema or chronic bronchitis (COPD other than asthma) are excluded.
2. 10. Participants who have received mAb therapy targeting IL-5/5R, IL-4R/IL-13, IL-33, IgE, or thymic stromal lymphpoietin (TSLP) within 12 months or 5 terminal phase half-lives of the drug, whichever is longer, prior to the screening. Authorized treatments for COVID-19 are permitted.
3. 11. Participants who have received treatment with an investigational drug within the past 30 days or 5 terminal phase half-lives of the drug whichever is longer, prior to the first dose of study intervention (this also includes investigational formulations of marketed products).
4. 12. Previously participated in any clinical study with biologic treatments for asthma (e.g., omalizumab, mepolizumab, dupilumab, reslizumab, benralizumab, other monoclonal antibodies (including Tezepelumab) or depemokimab and received study intervention (including placebo) within 12 months prior to the first dose of study intervention.
5. 13. A history (or suspected history) of alcohol misuse or substance abuse within 2 years prior to the first dose of study intervention.
6. 14. Current smokers or former smokers with a smoking history of 20 pack years (number of pack years = [number of cigarettes per day/20] x number of years smoked) and vapers.
7. 15. Participants with allergy/intolerance to a mAb or biologic or any of the excipients of depemokimab presented in Table 4.
8. 16. Participants who are pregnant or breastfeeding.
9. 17. Participants who have known evidence of lack of adherence to controller medications and/or ability to follow physician’s recommendations.
10. 18. Participants who: - have occupational ionizing-radiation exposure exceeding 10 mSV over 3 years as documented with a dosimeter. - have been exposed to elevated ionizing radiation from research imaging studies, for example: ▪ Participation in a research study with a single positron emission tomography scan in the past 3 years. ▪ Participation in a research study with 2 or more CT scans in the past 3 years in the following anatomical regions: chest, abdomen, cardiac, or spine."
11. 2. 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.
12. 19. Presence of metal objects that may interfere with chest CT quantification including presence of a cardiac pacemaker, defibrillator, metal prosthetic heart valve, metal projectile or metal weapon fragment (bullet, shrapnel, shotgun shot) or metal shoulder prosthesis.
13. 20. Evidence of clinically significant abnormality in the hematological, biochemical or urinalysis screen at screening (Visit 0), as judged by the investigator.
14. 3. Participants who developed an exacerbation within 4 weeks before screening. EXC#3
15. 4. Participants with a known, pre-existing parasitic infestation within 6 months prior to screening unless treated and evidenced to have been resolved.
16. 5. A known immunodeficiency (e.g. human immunodeficiency virus HIV), other than that explained by the use of CSs taken as therapy for asthma.
17. 6. A current malignancy or previous history of cancer in remission for less than 12 months prior to screening.
18. 7. Participants who have known, pre-existing, clinically significant cardiac, endocrine, autoimmune, metabolic, neurological, psychiatric, renal, gastrointestinal, hepatic, hematologic abnormalities or any other system abnormalities that are uncontrolled with standard treatment.
19. 8. Participants with current diagnosis of vasculitis.
20. 9. Participants who have received a previous documented failure with anti-IL-5/5R therapy.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change from baseline in total mucus plug volume measured at TLC at Week 26

Secondary endpoints 1

1. Change from baseline in airway wall thickness measured at TLC at Week 52.

Investigational products

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

Test 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

6 EU/EEA countries · 36 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 62 files

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

Application history

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