Efficacy and Safety of Depemokimab (GSK3511294) in Participants With Chronic Rhinosinusitis With Nasal Polyps (ANCHOR-2)

Study Overview
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Brief Summary
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This study will evaluate the efficacy and safety of depemokimab (GSK3511294) in participants with CRSwNP.

Official Title
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A Randomised, Double-blind, Parallel Group Phase III Study to Assess the Efficacy and Safety of 100 mg SC Depemokimab in Patients With Chronic Rhinosinusitis With Nasal Polyps (CRSwNP) - ANCHOR-2 (depemokimAb iN CHrOnic Rhinosinusitis)

Conditions
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Nasal Polyps

Intervention / Treatment
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* Biological: Depemokimab (GSK3511294)
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants with 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 at least one of the following at Visit 1: Previous nasal surgery for the removal of NP; Have used at least three consecutive days of systemic corticosteroids in the previous 2 years for the treatment of NP; Medically unsuitable or intolerant to systemic corticosteroid. Participants (except for those in Japan) must be on daily treatment with intranasal corticosteroids (INCS) (including intranasal liquid steroid wash/douching) for at least 8 weeks prior to screening. Participants presenting with severe NP symptoms defined as symptoms of nasal congestion/blockade/obstruction with moderate or severe severity and loss of smell or rhinorrhea (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), plus 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 upper respiratory tract infection (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. Liver Disease: Alanine aminotransferase (ALT) >2 times upper limit normal (ULN); Total bilirubin >1.5 times ULN (isolated bilirubin >1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin less than [<]35 percent [%]); 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. 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 enrollment. Hypersensitivity: Participants with allergy/intolerance to the excipients of depemokimab (GSK3511294) in a monoclonal antibody, or biologic. Participants that, according to the investigator's medical judgment, are likely to have active Coronavirus disease-2019 (COVID-19) infection must be excluded. Participants with known COVID-19 positive contacts within the past 14 days must be excluded for at least 14 days following the exposure during which the participant should remain symptom-free. Reported smell/ taste complications from COVID-19 must be used as exclusion. Participants that have been exposed to ionising 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. Previously participated in any study with 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Participants will receive either depemokimab (GSK3511294) or placebo during the study.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Participants receiving depemokimab (GSK3511294)<br> | Biological: Depemokimab (GSK3511294)<br>* Depemokimab (GSK3511294) will be administered using a pre-filled syringe.<br>|
| Placebo Comparator: Participants receiving Placebo<br> | Drug: Placebo<br>* Placebo will be administered as normal saline using a pre-filled syringe.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in total endoscopic nasal polyps (NP) score at Week 52 (scores on a scale) | NP score is graded based on NP size and recorded as the sum of the right and left nostril scores evaluated by nasal endoscopy. The total endoscopic NP score ranges between 0 (no polyps) to 8 (large polyps); higher scores indicate worse status. | Baseline and at Week 52 | 
| Change from Baseline in mean nasal obstruction score using verbal response scale (VRS) from Weeks 49 to 52 (scores on a scale) | Participants will be asked to indicate the severity of nasal obstruction at their 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). | Baseline and from Week 49 to Week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in mean symptom score for rhinorrhea (runny nose) using VRS (scores on a scale) | Participants will be asked to indicate the severity of rhinorrhea (runny nose) at their 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). | Baseline and from Week 49 to Week 52 | 
| Change from Baseline in mean symptom score for loss of smell using VRS (scores on a scale) | Participants will be asked to indicate the severity of loss of smell at their 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. | Baseline and from Week 49 to Week 52 | 
| Change from Baseline in Lund Mackay (LMK) computed tomography (CT) score (scores on a scale) | The LMK CT scoring system is based on CT imaging of the sinuses with points given for degree of opacification: 0 =normal, 1 = partial opacification, 2 = total opacification. These points are then applied to the maxillary, anterior ethmoid, posterior ethmoid, sphenoid, frontal sinus on each side (right and left). The osteomeatal complex (OC) is graded as 0 = not occluded, or 2 = occluded deriving a maximum score of 12 per side. The range for the total LMK CT score is therefore 0 (normal) to 24 (total opacification) when summed across both sides. | Baseline and at Week 52 | 
| Change from Baseline in Sino-nasal Outcome Test (SNOT)-22 total score (scores on a scale) | 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 (not present/no problem) to 5 (Problem as bad as it can be). The total score range for the SNOT-22 is 0-110, where higher scores indicate greater disease impact | Baseline and at Week 52 | 
| Change from Baseline in Asthma Control Questionnaire (ACQ-5) score (scores on a scale) | The ACQ-5 is a 5-item questionnaire which enquires about the frequency and/or severity of asthma symptoms over the previous week (nocturnal awakening on waking in the morning, activity limitation, and shortness of breath, wheeze). Each question is scored from 0 (no impairment/limitation) to 6 (total impairment/ limitation). Higher score indicates more limitations. Impact on asthma control in participants with an ACQ-5 score greater than (>)0.75 at Baseline will be assessed. | Baseline and at Week 52 | 
| Change from Baseline in mean nasal obstruction score using VRS from Weeks 21 to 24 (scores on a scale) | Participants will be asked to indicate the severity of nasal obstruction at their 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) ranging from 0 (no symptoms). | Baseline and from Week 21 to Week 24 | 
| Change from Baseline in total endoscopic NP score at Week 26 (scores on a scale) | NP score is graded based on NP size and recorded as the sum of the right and left nostril scores evaluated by nasal endoscopy. The total endoscopic NP score ranges between 0 (no polyps) to 8 (large polyps); higher scores indicate worse status. | Baseline and at Week 26 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Depemokimab, GSK3511294, Chronic rhinosinusitis, Verbal response scale, Asthma Control Questionnaire, Lund Mackay computed tomography, Nasal polyps score, Nasal endoscopy