Chronic Rhinosinusitis With Nasal Polyps (CRSwNP)
Conditions
Brief summary
This is a multicenter, randomized, double-blind, placebo-controlled study designed to evaluate the efficacy, safety, pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of AK139 injection compared with placebo in participants with chronic rhinosinusitis with nasal polyps (CRSwNP) receiving background treatment with mometasone furoate nasal spray (MFNS).
Detailed description
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.
Interventions
BIOLOGICALAK139
AK139 administered subcutaneously
BIOLOGICALPlacebo
Placebo administered subcutaneously
Sponsors
Akeso
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Male or female participants aged 18 to 75 years (inclusive) at the time of signing the informed consent form (ICF). 2. Bilateral CRSwNP with prior treatment with systemic corticosteroids (SCS), contraindications to or intolerance of SCS, and/or prior nasal polyp surgery. 3. Nasal Polyp Score (NPS) ≥5, with a minimum score of 2 in each nasal cavity, at screening and baseline. 4. Ongoing nasal congestion/obstruction, with a Nasal Congestion Score (NCS) of 2 or 3 at screening and baseline. 5. Use of intranasal corticosteroids for at least 4 weeks prior to screening.
Exclusion criteria
1. 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). 2. Presence of any of the following conditions: * Antrochoanal polyp; * Persistent rhinitis medicamentosa; * Allergic fungal rhinosinusitis with symptoms and/or CT findings. 3. Nasal malignant or benign tumors. 4. Severe nasal septal deviation causing obstruction of at least one nostril. 5. Known eosinophilic granulomatosis with polyangiitis, granulomatosis with polyangiitis, cystic fibrosis, primary ciliary dyskinesia, or other systemic diseases associated with nasal polyposis. 6. Participants with asthma and FEV1 ≤50% of the predicted value at screening or baseline. 7. Parasitic infection, active tuberculosis, recurrent or chronic infectious diseases, or autoimmune diseases. 8. Acute sinusitis, nasal infection, or upper respiratory tract infection within 2 weeks prior to screening or during the screening period. 9. Chronic infection with hepatitis B virus, hepatitis C virus, human immunodeficiency virus (HIV), or syphilis. 10. 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. 11. 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. 12. Prior treatment with anti-IL-4Rα monoclonal antibodies with inadequate clinical response.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Nasal Polyp Score (NPS) | Baseline and Week 16 | Change from baseline in Nasal Polyp Score (NPS). NPS is a bilateral endoscopic assessment scale for nasal polyposis, where each nasal cavity is scored from 0 to 4. The total score is the sum of the left and right sides, ranging from 0 to 8, with higher scores indicating more severe nasal polyp disease. |
| Nasal Congestion Score (NCS) | Baseline and Week 16 | Change from baseline in Nasal Congestion Score (NCS). NCS is a patient-reported outcome measure using a 4-point Verbal Rating Scale (VRS) ranging from 0 to 3. Higher scores indicate more severe nasal congestion. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Nasal Polyp Score (NPS) | From baseline to Week 20 (excluding Week 16) | Change from baseline in Nasal Polyp Score (NPS) at each assessment visit. |
| Nasal Congestion Score (NCS) | From baseline through Week 20 (excluding Week 16) | Change from baseline in Nasal Congestion Score (NCS) at each assessment visit. |
| Total Symptom Score (TSS) | From baseline to Week 20 | Change from baseline in Total Symptom Score (TSS) at each assessment visit. TSS ranged from 0 to 9, with higher scores indicating greater nasal symptom severity. |
| Sino-Nasal Outcome Test-22 (SNOT-22) | From baseline to Week 20 | Change from baseline in Total Score of Sino-Nasal Outcome Test-22 (SNOT-22) at each assessment visit. SNOT-22 is a validated patient-reported questionnaire used to assess symptom severity and health-related quality of life (HRQoL) in patients with chronic rhinosinusitis (CRS). Scores range from 0 to 110, with higher scores indicating greater symptom burden and poorer HRQoL. |
| Lund-Mackay Score | Baseline and Week 16 | Change from baseline in Lund-Mackay Score on CT scan. The Lund-Mackay score ranges from 0 to 24, with higher scores indicating more severe sinonasal disease. |
| Safety parameters | Up to Week 20 | Assessment of safety, including treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and clinically significant findings from physical examinations, laboratory tests, vital signs, and 12-lead electrocardiograms (ECGs). |
| Pharmacokinetics (PK) | Up to Week 20 | Serum concentrations of AK139 following administration. |
| Pharmacodynamics (PD) | From baseline to Week 20 | Change from baseline in serum biomarker levels. |
| Anti-drug Antibodies (ADA) and Neutralizing Antibodies (NAb) | Up to Week 20 | Incidence of Anti-drug antibodies(ADA) and Neutralizing antibody (Nab) after treatment. |
Countries
China
Contacts
CONTACTGuoqin Wang
Outcome results
None listed