Subcutaneously CM310/Placebo in Patients With Chronic Rhinosinusitis With Nasal Polyposis (CROWNS-1)

Study Overview
=================
Brief Summary
-----------------
This is a multi-center, randomized, double blind, placebo-controlled study to evaluate the efficacy, safety, PK, PD and immumogenicity of CM310 in comparison to placebo in addition to a background treatment of mometasone furcate nasal spray (MFNS) in patients with chronic rhinosinusitis with nasal polyposis (CRSwNP).

Detailed Description
-----------------
The study consists of a Screening/run-in Period (up to 4 weeks), a Randomized, Double Blind Treatment Period (16 weeks, till End-of-Treatment Visit) and a Safety Follow-up Period (8 weeks, till End-of-Study Visit). 56 patients who meet eligibility criteria will be randomized 1:1 to receive either CM310 300mg or matched placebo subcutaneously every two weeks (Q2W) for a total of 8 times. All patients will receive MFNS on a daily basis as a background treatment throughout the study. MFNS is required to use no less than 14 days during Screening/run-in Period. Central reading will be implemented to nasal endoscopic nasal polyp score (NPS) , CT scans to Lund-Mackay score and volume of the involved area of nasosinusitis on 3D-construction images, and nasal polyp biopsy tissue analysis to eosinophil counts & percentage.

Official Title
-----------------
A Randomized, Double Blind, Placebo-Controlled Phase 2 Study to Evaluate the Efficacy, Safety, PK, PD and Immunogenicity of Subcutaneously Given Multiple-Dose CM310 in Patients With Chronic Rhinosinusitis With Nasal Polyps (CRSwNP)

Conditions
-----------------
Chronic Rhinosinusitis (Diagnosis), Nasal Polyps

Intervention / Treatment
-----------------
* Biological: CM310
* Biological: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Bilateral CRSwNP. Prior treatment with systemic corticosteroids (SCS), and/or contraindicate to or intolerance to SCS, and/or with prior surgery to nasal polyps. Stable dose of intranasal corticosteroids for at least 4 weeks before screening. Ongoing symptoms for at least 4 weeks before screening：1)Nasal congestion/obstruction; 2)Othe symptom, e.g., loss of smell or rhinorrhea. Bilateral NPS of ≥5 with a minimum score of 2 in each nasal cavity at screening and at baseline. NCS score of 2 or 3 at screening and at baseline. Eosinophilic level meets the one of the following criteria: 1) serum eosinophil count ≥6.9% (without concomitant asthma) or ≥3.7% (with concomitant asthma) at screening; 2) absolute count of ≥55 per high power field or percentage of ≥27% in eosinophil level from nasal polyps biospy tissue. Contraception. Exclusion Criteria: Not enough washingout period for previous therapy, e.g., less than 10 weeks or 5 half-lives (whichever is longer) for IL-4Rα antagonists, less than 8 weeks or 5 half-lives for biologic therapy/systemic immunosuppressant, less than 6 months for sinus surgery (including polypectomy). concurrent disease, e.g., ongoing rhinitis medicamentosa, acute sinusitis, nasal infection or upper respiratory infection, allergic fungal rhinosinusitis, malignancy, uncontrolled chronic disease such as cardivascular diseases, tuberculosis, diabetes etc. Allergic or intolerant to mometasone furoate spray or CM310/placebo. Significant liver or renal dysfunction. Other.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CM310<br>CM310 300mg is given subcutaneously (SC) every two weeks for 16-week treatment | Biological: CM310<br>* 300 mg every two weeks<br>|
| Placebo Comparator: Placebo<br>Placebo is given subcutaneously (SC) every two weeks for 16-week treatment. | Biological: Placebo<br>* 300 mg every two weeks<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bilateral endoscopic Nasal Polyps Score (NPS) | Change from baseline in the bilateral endoscopic NPS.NPS score ranges from 0-8. (sum of 0-4 for each nasal passage scores), higher score means a worse outcome. | at Week 16 | 
| Nasal Congestion/Obstruction SymptomSeverity (NCS) Score | Change from baseline in the NCS score. NCS score (0-3), higher score means worse nasal symptom. | at Week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to the first response of NPS | Time to the first response of NPS (defined as bilateral endoscopic NPS improved ≥1). | Baseline up to Week 24 | 
| Lund-Mackay score | Change from baseline in the Lund-Mackay score on CT scan. The range of LM score is 0-24. Higher score means worse nasosinusitis. | at Week 16 | 
| Volume of the involved area of nasosinusitis on 3D-construction CT scan | Change from baseline in the volume of the involved area of nasosinusitis on 3D-construction CT scan. | at Week 16 | 
| Bilateral endoscopic NPS | Change from baseline in the bilateral endoscopic NPS. | at Week 8 | 
| Proportion of subjects receiving rescue therapy for nasal polyps | Proportion of subjects receiving rescue therapy for nasal polyps. | Baseline up to Week 24 | 
| University of Pennsylvania Smell Identification Test (UPSIT) | Change from baseline in UPSIT. UPSIT score (0-40). Higher score means better sense of smell. | at Week 16 | 
| 22-item Sino-nasal Outcome Test Scores(SNOT-22) score | Change from baseline in SNOT-22 score. SNOT-22 score (0-110). Higher score means a worse outcome. | at Week 16 | 
| Total Symptom Score(TSS) score | Change from baseline in TSS score. TSS score (0-9). Higher score means worse nasal symptom. | at Week 16 | 
| Bilateral endoscopic NPS | Change from baseline in the bilateral endoscopic NPS in subjects with concurrent asthma. | at Week 16 | 
| Bilateral endoscopic NCS | Change from baseline in the NCS in subjects with concurrent asthma. | at Week 16 | 
| Safety parameters | Incidence of treatment-emergent adverse events (TEAEs), of treatment-emergent serious AEs (TESAEs), etc. | Baseline up to Week 24 | 
| Pharmacokinetics(PK) | Trough concentration and exposure. | Baseline up to Week 24 | 
| Pharmacodynamics(PD) | Change from baseline in serum biomarker level (TARC, total IgE and eosinophil level). | Baseline up to Week 24 | 
| PD(eosinophil level in nasal polyps biospy tissue) | Change from baseline of eosinophil level in nasal polyps biospy tissue. | at Week 16 | 
| Anti-drug antibodies(ADA) | Incidence of ADA. | Baseline up to Week 24 | 
| Neutralizing antibody (Nab) | Incidence of Nab. | Baseline up to Week 24 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Chronic Rhinosinusitis with Nasal Polyps