Chronic Rhinosinusitis (Diagnosis), Nasal Polyps
Conditions
Keywords
Chronic Rhinosinusitis with Nasal Polyps
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.
Interventions
BIOLOGICALCM310
300 mg every two weeks
BIOLOGICALPlacebo
300 mg every two weeks
Sponsors
Keymed Biosciences Co.Ltd
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 70 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Bilateral endoscopic Nasal Polyps Score (NPS) | at Week 16 | 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. |
| Nasal Congestion/Obstruction SymptomSeverity (NCS) Score | at Week 16 | Change from baseline in the NCS score. NCS score (0-3), higher score means worse nasal symptom. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Volume of the involved area of nasosinusitis on 3D-construction CT scan | at Week 16 | Change from baseline in the volume of the involved area of nasosinusitis on 3D-construction CT scan. |
| Bilateral endoscopic NPS | at Week 8 | Change from baseline in the bilateral endoscopic NPS. |
| Proportion of subjects receiving rescue therapy for nasal polyps | Baseline up to Week 24 | Proportion of subjects receiving rescue therapy for nasal polyps. |
| University of Pennsylvania Smell Identification Test (UPSIT) | at Week 16 | Change from baseline in UPSIT. UPSIT score (0-40). Higher score means better sense of smell. |
| 22-item Sino-nasal Outcome Test Scores(SNOT-22) score | at Week 16 | Change from baseline in SNOT-22 score. SNOT-22 score (0-110). Higher score means a worse outcome. |
| Total Symptom Score(TSS) score | at Week 16 | Change from baseline in TSS score. TSS score (0-9). Higher score means worse nasal symptom. |
| Time to the first response of NPS | Baseline up to Week 24 | Time to the first response of NPS (defined as bilateral endoscopic NPS improved ≥1). |
| Safety parameters | Baseline up to Week 24 | Incidence of treatment-emergent adverse events (TEAEs), of treatment-emergent serious AEs (TESAEs), etc. |
| Pharmacokinetics(PK) | Baseline up to Week 24 | Trough concentration and exposure. |
| Pharmacodynamics(PD) | Baseline up to Week 24 | Change from baseline in serum biomarker level (TARC, total IgE and eosinophil level). |
| PD(eosinophil level in nasal polyps biospy tissue) | at Week 16 | Change from baseline of eosinophil level in nasal polyps biospy tissue. |
| Anti-drug antibodies(ADA) | Baseline up to Week 24 | Incidence of ADA. |
| Neutralizing antibody (Nab) | Baseline up to Week 24 | Incidence of Nab. |
| Bilateral endoscopic NCS | at Week 16 | Change from baseline in the NCS in subjects with concurrent asthma. |
| Lund-Mackay score | at Week 16 | Change from baseline in the Lund-Mackay score on CT scan. The range of LM score is 0-24. Higher score means worse nasosinusitis. |
Countries
China
Outcome results
None listed