Clinical trial NCT04805398: Subcutaneously CM310/Placebo in Patients With Chronic Rhinosinusitis With Nasal Polyposis (CROWNS-1)
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chronic Rhinosinusitis (Diagnosis)
Nasal Polyps
Keywords: Chronic Rhinosinusitis with Nasal Polyps
Lead sponsor: Keymed Biosciences Co.Ltd
Sponsor class: INDUSTRY
First posted: 2021-03-18
Enrollment: 56
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Bilateral endoscopic Nasal Polyps Score (NPS)
timeFrame: at Week 16
measure: Nasal Congestion/Obstruction SymptomSeverity (NCS) Score
timeFrame: at Week 16
Secondary outcomes:
measure: Time to the first response of NPS
timeFrame: Baseline up to Week 24
measure: Lund-Mackay score
timeFrame: at Week 16
measure: Volume of the involved area of nasosinusitis on 3D-construction CT scan
timeFrame: at Week 16
measure: Bilateral endoscopic NPS
timeFrame: at Week 8
measure: Proportion of subjects receiving rescue therapy for nasal polyps
timeFrame: Baseline up to Week 24
measure: University of Pennsylvania Smell Identification Test (UPSIT)
timeFrame: at Week 16
measure: 22-item Sino-nasal Outcome Test Scores(SNOT-22) score
timeFrame: at Week 16
measure: Total Symptom Score(TSS) score
timeFrame: at Week 16
measure: Bilateral endoscopic NPS
timeFrame: at Week 16
measure: Bilateral endoscopic NCS
timeFrame: at Week 16
measure: Safety parameters
timeFrame: Baseline up to Week 24
measure: Pharmacokinetics(PK)
timeFrame: Baseline up to Week 24
measure: Pharmacodynamics(PD)
timeFrame: Baseline up to Week 24
measure: PD(eosinophil level in nasal polyps biospy tissue)
timeFrame: at Week 16
measure: Anti-drug antibodies(ADA)
timeFrame: Baseline up to Week 24
measure: Neutralizing antibody (Nab)
timeFrame: Baseline up to Week 24
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Chaoyang Hospital, CMU
state: Beijing
city: Beijing
country: China
facility: Beijing Hospital
state: Beijing
city: Beijing
country: China
facility: Beijing Renmin Hospital
state: Beijing
city: Beijing
country: China
facility: Beijing Tongren Hospital, CMU
state: Beijing
city: Chongqing
country: China
facility: First Affiliated Hospital of Chongqing Medical University
state: Chongqing
city: Jingzhou
country: China
facility: Jingzhou Central Hospital
state: Hubei
city: Wuhan
country: China
facility: Renmin Hospital of Wuhan University
state: Hubei
city: Wuhan
country: China
facility: Union Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology
state: Hubei
city: Changsha
country: China
facility: Third Xiangya Hospital of Central South University
state: Hunan
city: Nanchang
country: China
facility: The First Affiliated Hospital of Nanchang University
state: Jiangxi
city: Qingdao
country: China
facility: Affiliated Hospital of Qingdao University
state: Shandong
city: Yantai
country: China
facility: Yantai Yuhuangding Hospital
state: Shandong
city: Jinan
country: China
facility: Shandong Second Provincial General Hospital (Shandong ENT hospital)
state: Shangdong
city: Shanghai
country: China
facility: Renji Hospital of Shanghai Jiaotong University School of Medicine
state: Shanghai
city: Shanghai
country: China
facility: Tongji Hospital of Tongji University
state: Shanghai
city: Taiyuan
country: China
facility: Second Hospital of Shanxi Medical University
state: Shanxi
city: Chengdu
country: China
facility: Hospital of Chengdu University of Traditional Chinese Medicine
state: Sichuan
city: Chengdu
country: China
facility: West China Hospital of Sichuan University
state: Sichuan
city: Hangzhou
country: China
facility: Zhejiang Provincial People's Hospital
state: Zhejiang
Study officials:
affiliation: Beijing Tongren Hospital, CMU
name: Luo Zhang
role: PRINCIPAL_INVESTIGATOR
References: