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

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