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

Nasal Polyps Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04805398
• Other study ID #: CM310NP001
• Status: Completed
• Phase: Phase 2
• Start date: April 6, 2021
• Est. completion date: March 18, 2022

Study information

• Verified date: November 2021
• Source: Keymed Biosciences Co.Ltd
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 56
• Est. completion date: March 18, 2022
• Est. primary completion date: March 18, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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-4Ra 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.

Related Conditions & MeSH terms

• Chronic Rhinosinusitis (Diagnosis)
• Nasal Polyps
• Polyps
• Sinusitis

Intervention

Biological:
• CM310
300 mg every two weeks
• Placebo
300 mg every two weeks

Locations

Country	Name	City	State
China	Beijing Chaoyang Hospital, CMU	Beijing	Beijing
China	Beijing Hospital	Beijing	Beijing
China	Beijing Renmin Hospital	Beijing	Beijing
China	Beijing Tongren Hospital, CMU	Beijing	Beijing
China	Third Xiangya Hospital of Central South University	Changsha	Hunan
China	Hospital of Chengdu University of Traditional Chinese Medicine	Chengdu	Sichuan
China	West China Hospital of Sichuan University	Chengdu	Sichuan
China	First Affiliated Hospital of Chongqing Medical University	Chongqing	Chongqing
China	Zhejiang Provincial People's Hospital	Hangzhou	Zhejiang
China	Shandong Second Provincial General Hospital (Shandong ENT hospital)	Jinan	Shangdong
China	Jingzhou Central Hospital	Jingzhou	Hubei
China	The First Affiliated Hospital of Nanchang University	Nanchang	Jiangxi
China	Affiliated Hospital of Qingdao University	Qingdao	Shandong
China	Renji Hospital of Shanghai Jiaotong University School of Medicine	Shanghai	Shanghai
China	Tongji Hospital of Tongji University	Shanghai	Shanghai
China	Second Hospital of Shanxi Medical University	Taiyuan	Shanxi
China	Renmin Hospital of Wuhan University	Wuhan	Hubei
China	Union Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology	Wuhan	Hubei
China	Yantai Yuhuangding Hospital	Yantai	Shandong

Sponsors (1)

Lead Sponsor	Collaborator
Keymed Biosciences Co.Ltd

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	Bilateral endoscopic NPS	Change from baseline in the bilateral endoscopic NPS.	at Week 8
Secondary	Proportion of subjects receiving rescue therapy for nasal polyps	Proportion of subjects receiving rescue therapy for nasal polyps.	Baseline up to Week 24
Secondary	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
Secondary	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
Secondary	Total Symptom Score(TSS) score	Change from baseline in TSS score. TSS score (0-9). Higher score means worse nasal symptom.	at Week 16
Secondary	Bilateral endoscopic NPS	Change from baseline in the bilateral endoscopic NPS in subjects with concurrent asthma.	at Week 16
Secondary	Bilateral endoscopic NCS	Change from baseline in the NCS in subjects with concurrent asthma.	at Week 16
Secondary	Safety parameters	Incidence of treatment-emergent adverse events (TEAEs), of treatment-emergent serious AEs (TESAEs), etc.	Baseline up to Week 24
Secondary	Pharmacokinetics(PK)	Trough concentration and exposure.	Baseline up to Week 24
Secondary	Pharmacodynamics(PD)	Change from baseline in serum biomarker level (TARC, total IgE and eosinophil level).	Baseline up to Week 24
Secondary	PD(eosinophil level in nasal polyps biospy tissue)	Change from baseline of eosinophil level in nasal polyps biospy tissue.	at Week 16
Secondary	Anti-drug antibodies(ADA)	Incidence of ADA.	Baseline up to Week 24
Secondary	Neutralizing antibody (Nab)	Incidence of Nab.	Baseline up to Week 24