Efficacy and Safety of Depemokimab Monotherapy Without Concomitant Use of Intranasal Corticosteroids (INCS) in Japanese Participants With Chronic Rhinosinusitis With Nasal Polyps (CRSwNP)

A Phase IV, Single-arm, Open-label Study to Evaluate the Efficacy and Safety of 100 mg SC Depemokimab Monotherapy Without Concomitant Use of Intranasal Corticosteroids (INCS) in Japanese Participants With Chronic Rhinosinusitis With Nasal Polyps (CRSwNP) Who Are Inadequately Controlled With Standard Treatment

This study will evaluate the efficacy and safety of depemokimab (GSK3511294) without concomitant use of Intranasal corticosteroids (INCS) in participants with Chronic rhinosinusitis with nasal polyps (CRSwNP).

Study Overview

• Status: Not yet recruiting
• Conditions: Nasal Polyps
• Intervention / Treatment: Biological: Depemokimab

• Study Type: Interventional
• Enrollment (Estimated): 28
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: US GSK Clinical Trials Call Center; Phone Number: 877-379-3718; Email: GSKClinicalSupportHD@gsk.com
• Study Contact Backup: Name: EU GSK Clinical Trials Call Center; Phone Number: +44 (0) 20 89904466; Email: GSKClinicalSupportHD@gsk.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 18 years of age and older inclusive, at the time of signing the informed consent
• Endoscopic bilateral NP score of at least 5 out of a maximum score of 8 (with a minimum score of 2 in each nasal cavity) assessed by the investigator
• Participants who have had previous nasal surgery for the removal of nasal polyps, have used at least three consecutive days of systemic corticosteroids in the previous 2 years for the treatment of nasal polyps, or are medically unsuitable or intolerant to systemic corticosteroid
• Participants presenting with severe nasal polyp symptoms defined as symptoms of nasal congestion/blockade/obstruction with moderate or severe severity and loss of smell or rhinorrhoea (runny nose) based on clinical assessment by the investigator
• Presence of symptoms of chronic rhinosinusitis as described by at least 2 different symptoms for at least 12 weeks prior to Visit 1, one of which should be either nasal blockage/obstruction/congestion or nasal discharge (anterior/posterior nasal drip), or facial pain/pressure and/or reduction or loss of smell
• Male or eligible female participants

Exclusion Criteria:

• As a result of medical interview, physical examination, or screening investigation the physician responsible considers the participant unfit for the study
• Cystic fibrosis
• Antrochoanal polyps
• Nasal cavity tumor (malignant or benign)
• Fungal rhinosinusitis
• Severe nasal septal deviation occluding one nostril preventing full assessment of nasal polyps in both nostrils
• Participants who had a sino-nasal or sinus surgery changing the lateral wall structure of the nose making impossible the evaluation of nasal polyp score
• Acute sinusitis or URTI at screening or in 2 weeks prior to screening
• Ongoing rhinitis medicamentosa (rebound or chemical induced rhinitis)
• Participants who have had an asthma exacerbation requiring admission to hospital within 4 weeks of screening
• Participants who have undergone any intranasal and/or sinus surgery (for example polypectomy, balloon dilatation or nasal stent insertion) within 6 months prior to Visit 1; nasal biopsy prior to Visit 1 for diagnostic purposes only is excepted.
• Participants where NP surgery is contraindicated in the opinion of the Investigator
• 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
• Participants with a known, pre-existing parasitic infestation within 6 months prior to Visit 1
• A known immunodeficiency (e.g., human immunodeficiency virus - HIV), other than that explained by the use of corticosteroids (CSs) taken as therapy for asthma
• A current malignancy or previous history of cancer in remission for less than 12 months prior to screening.NOTE: Participants that had localised carcinoma of the skin which was resected for cure will not be excluded
• Participants who have known, pre-existing, clinically significant cardiac, endocrine, autoimmune, metabolic, neurological, renal, gastrointestinal, hepatic, hematological or any other system abnormalities that are uncontrolled with standard treatment
• Participants with current diagnosis of vasculitis. Participants with high clinical suspicion of vasculitis at screening will be evaluated and current vasculitis must be excluded prior to enrolment
• Participants with allergy/intolerance to the excipients of depemokimab, a monoclonal antibody, or biologic
• Participants that have been exposed to ionizing radiation in excess of 10 millisievert (mSv) above background over the previous 3-year period as a result of occupational exposure or previous participation in research studies
• Participants using INCS (including intranasal liquid steroid wash/douching) for at least 8 weeks immediately prior to screening
• Participants on inhaled corticosteroids exhalation through nose (Inhaled corticosteroids exhalation through nose [ICS/ETN]) method of administration for their asthma and NP for at least the 8 weeks immediately prior to screening
• Participants who have received depemokimab (Exdensur), mepolizumab (Nucala), reslizumab (Cinqair/Cinqaero), or benralizumab (Fasenra) within 12 months prior to Visit 1 or experienced treatment failure with monoclonal antibodies targeting IL-5/5R
• Participants who have received omalizumab (Xolair), dupilumab (Dupixent) or Tezpelumab (Tezpire) within 130 days prior to Visit 1
• Previously participated in any study with depemokimab, mepolizumab, reslizumab, or benralizumab and received study intervention (including placebo) within 12 months prior to Visit 1
• Women who are pregnant or lactating or are planning on becoming pregnant during the study
• ALT >2* ULN
• Total bilirubin >1.5* ULN; For participants with Gilbert's syndrome can be included with total bilirubin >1.5* ULN if direct bilirubin is <=1.5* ULN
• Cirrhosis or current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Depemokimab + SoC; Participants will receive depemokimab along with their existing baseline maintenance CRSwNP standard of care (SOC) treatment (excluding INCS).	Biological: Depemokimab; Participants will receive depemokimab.; Other Names: GSK3511294

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Achieving a One-point or Greater Decrease from Baseline in Total Endoscopic Nasal Polyp (NP) Score Without First Having Nasal Surgery (Actual) or Disease-Modulating Medication for CRSwNP	The total endoscopic NP score will evaluate the size and extent of nasal polyps via endoscopy. The assessments will be performed using centrally reviewed video recordings of nasal endoscopy. The right and left nostrils will be scored from 0 to 4 (0 = No polyps; 1 = Small polyps in the middle meatus not reaching below the inferior border of the middle concha; 2 = Polyps reaching below the lower border of the middle turbinate; 3 = Large polyps reaching the lower border of the inferior turbinate or polyps medial to the middle concha; and 4 = Large polyps causing complete obstruction of the inferior meatus). The scores will be graded based on NP size and will be recorded as the sum of the right and left nostril scores, ranging from 0 (no polyps) to 8 (large polyps), calculated by summing the scores [0 to 4] in each nostril, with higher scores indicating worse status.	At Week 52

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline in Total Endoscopic NP Score	The total endoscopic NP score will evaluate the size and extent of nasal polyps via endoscopy. The assessments will be performed using centrally reviewed video recordings of nasal endoscopy. The right and left nostrils will be scored from 0 to 4 (0 = No polyps; 1 = Small polyps in the middle meatus not reaching below the inferior border of the middle concha; 2 = Polyps reaching below the lower border of the middle turbinate; 3 = Large polyps reaching the lower border of the inferior turbinate or polyps medial to the middle concha; and 4 = Large polyps causing complete obstruction of the inferior meatus). The scores will be graded based on NP size and will be recorded as the sum of the right and left nostril scores, ranging from 0 (no polyps) to 8 (large polyps), calculated by summing the scores [0 to 4] in each nostril, with higher scores indicating worse status.	Baseline (Day 1) and Week 52
Change from Baseline in Mean Nasal Obstruction Score Using Verbal Response Scale (VRS)	Participants will use a VRS to rate nasal obstruction severity, with scores to be averaged over the specified period to assess treatment impact on nasal obstruction symptoms. Participants will be asked to indicate the severity of nasal obstruction at its worst over the last 24 hours using a 4-point VRS, with options of no symptoms, mild symptoms, moderate symptoms, and severe symptoms. This will be scored on a scale ranging from 0 (no symptoms) to 3 (severe symptoms), with higher scores indicating worse status. The average of daily scores in 4-weekly intervals will be calculated, and data will be presented for Weeks 49-52.	Baseline (Day 1) and from Week 49 through to Week 52
Change from Baseline in Mean Symptom Score for Rhinorrhoea (Runny Nose) Using VRS	Participants will be asked to indicate the severity of rhinorrhoea (runny nose) at its worst over the last 24 hours using a 4-point VRS, with options of no symptoms, mild symptoms, moderate symptoms, and severe symptoms. This will be scored on a scale ranging from 0 (no symptoms) to 3 (severe symptoms), with higher scores indicating worse status. The average of daily scores in 4-weekly intervals will be calculated, and data will be presented for Weeks 49-52.	Baseline (Day 1) and from Week 49 through to Week 52
Change from Baseline in Mean Symptom Score for Loss of Smell Using VRS	Participants will be asked to indicate the severity of loss of smell at its worst over the last 24 hours using a 4-point VRS, with options of no symptoms, mild symptoms, moderate symptoms, and severe symptoms. This will be scored on a scale ranging from 0 (no symptoms) to 3 (severe symptoms), with higher scores indicating worse status. The average of daily scores in 4-weekly intervals will be calculated, and data will be presented for Weeks 49-52.	Baseline (Day 1) and from Week 49 through to Week 52
Change from baseline in Lund Mackay Computerised Tomography (CT) score	The LMK CT scoring system is based on CT imaging of the sinuses, with points to be given for the degree of opacification: 0 = normal, 1 = partial opacification, and 2 = total opacification. These points will be applied to the maxillary, anterior ethmoid, posterior ethmoid, sphenoid, and frontal sinuses on each side (right and left). The osteomeatal complex (OC) will be graded as 0 = not occluded or 2 = occluded. The range for the total LMK CT score will therefore be 0 (normal) to 24 (total opacification) when summed across both sides, with higher scores indicating more severe disease.	Baseline (Day 1) and Week 52
Change from Baseline in Sino-nasal Outcome Test (SNOT)-22 Score	The SNOT-22 is a 22-item measure of disease-specific health-related quality of life (HRQoL). Participants will be asked to rate the severity of their condition on each of the 22 items over the previous 2 weeks using a 6-point rating scale of 0-5, including: 0 = Not present/no problem; 1 = Very mild problem; 2 = Mild or slight problem; 3 = Moderate problem; 4 = Severe problem; and 5 = Problem "as bad as it can be." The scores for each question will be summed to derive the total score, with the SNOT-22 total score ranging from 0 (high quality of life) to 110 (worst quality of life), where higher scores will indicate worse quality of life.	Baseline (Day 1) and Week 52

Collaborators and Investigators

• Sponsor: GlaxoSmithKline
• Investigators: Study Director: GSK Clinical Trials, GlaxoSmithKline

Study record dates

Study Major Dates

• Study Start (Estimated): July 20, 2026
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): June 16, 2028

Study Registration Dates

• First Submitted: July 9, 2026
• First Submitted That Met QC Criteria: July 9, 2026
• First Posted (Actual): July 14, 2026

Study Record Updates

• Last Update Posted (Actual): July 14, 2026
• Last Update Submitted That Met QC Criteria: July 9, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: Safety; Efficacy; Japanese participants; Monotherapy; CRSwNP; Depemokimab; Chronic rhinosinusitis with nasal polyps; GSK3511294; Phase IV clinical trial
• Additional Relevant MeSH Terms: Pathological Conditions, Anatomical; Respiratory Tract Diseases; Nose Diseases; Otorhinolaryngologic Diseases; Polyps; Pathological Conditions, Signs and Symptoms; Nasal Polyps
• Other Study ID Numbers: 307355

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Study Sponsor will assess requests from qualified researchers for anonymized individual patient-level data and related study documents. Data sharing is subject to certain criteria, conditions, and exceptions. For further information, refer to https://www.gsk-studyregister.com/gsk-patient-level-data-sharing-july2025.pdf
• IPD Sharing Time Frame: Anonymized IPD will be made available within 6 months of publication of primary, key secondary and safety results for studies in product with approved indication(s) or asset(s) with development terminated across all indications.
• IPD Sharing Access Criteria: Anonymized IPD is shared with researchers whose proposals are approved by an Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months, but an extension may be granted, when justified, for up to 6 months.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No