A Study to Evaluate the Efficacy and Safety of AK139 in Participants With Chronic Rhinosinusitis With Nasal Polyps

This is a multicenter, randomized, double-blind, placebo-controlled Phase II study designed to evaluate the efficacy, safety, pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of AK139 in participants with chronic rhinosinusitis with nasal polyps (CRSwNP).

Eligible participants will be randomized to receive AK139 or placebo in addition to background treatment with mometasone furoate nasal spray (MFNS). The study will assess the effect of AK139 on nasal polyp burden, disease symptoms, health-related quality of life, safety, PK, PD, and immunogenicity throughout the study period.

Inclusion criteria

• Male or female participants aged 18 to 75 years (inclusive) at the time of signing the informed consent form (ICF).
• Bilateral CRSwNP with prior treatment with systemic corticosteroids (SCS), contraindications to or intolerance of SCS, and/or prior nasal polyp surgery.
• Nasal Polyp Score (NPS) ≥5, with a minimum score of 2 in each nasal cavity, at screening and baseline.
• Ongoing nasal congestion/obstruction, with a Nasal Congestion Score (NCS) of 2 or 3 at screening and baseline.
• Use of intranasal corticosteroids for at least 4 weeks prior to screening.

Exclusion criteria

• History of sinonasal surgery (including nasal polypectomy) within 6 months prior to screening, or prior nasal surgery resulting in structural changes that preclude adequate assessment of Nasal Polyp Score (NPS).
• Presence of any of the following conditions:

• Antrochoanal polyp;
• Persistent rhinitis medicamentosa;
• Allergic fungal rhinosinusitis with symptoms and/or CT findings.
• Nasal malignant or benign tumors.
• Severe nasal septal deviation causing obstruction of at least one nostril.
• Known eosinophilic granulomatosis with polyangiitis, granulomatosis with polyangiitis, cystic fibrosis, primary ciliary dyskinesia, or other systemic diseases associated with nasal polyposis.
• Participants with asthma and FEV1 ≤50% of the predicted value at screening or baseline.
• Parasitic infection, active tuberculosis, recurrent or chronic infectious diseases, or autoimmune diseases.
• Acute sinusitis, nasal infection, or upper respiratory tract infection within 2 weeks prior to screening or during the screening period.
• Chronic infection with hepatitis B virus, hepatitis C virus, human immunodeficiency virus (HIV), or syphilis.
• Treatment with anti-IL-4Rα monoclonal antibodies, anti-thymic stromal lymphopoietin (TSLP) monoclonal antibodies, anti-immunoglobulin E (IgE) monoclonal antibodies, or other biologic agents within 10 weeks or 5 half-lives (whichever is longer) before randomization, or prior treatment with AK139.
• Treatment with short- or intermediate-acting systemic corticosteroids within 4 weeks prior to screening, or long-acting systemic corticosteroids within 6 weeks prior to screening.
• Prior treatment with anti-IL-4Rα monoclonal antibodies with inadequate clinical response.