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

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)

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).

Study Overview

• Status: Completed
• Conditions: Chronic Rhinosinusitis (Diagnosis); Nasal Polyps
• Intervention / Treatment: Biological: CM310; Biological: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 56
• Phase: Phase 2

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 68 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

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

Collaborators and Investigators

• Sponsor: Keymed Biosciences Co.Ltd
• Investigators: Principal Investigator: Luo Zhang, Beijing Tongren Hospital, CMU

Study record dates

Study Major Dates

• Study Start (Actual): April 6, 2021
• Primary Completion (Actual): March 18, 2022
• Study Completion (Actual): March 18, 2022

Study Registration Dates

• First Submitted: March 12, 2021
• First Submitted That Met QC Criteria: March 17, 2021
• First Posted (Actual): March 18, 2021

Study Record Updates

• Last Update Posted (Actual): June 29, 2022
• Last Update Submitted That Met QC Criteria: June 23, 2022
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Keywords: Chronic Rhinosinusitis with Nasal Polyps
• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Otorhinolaryngologic Diseases; Pathological Conditions, Anatomical; Paranasal Sinus Diseases; Nose Diseases; Sinusitis; Nasal Polyps; Polyps
• Other Study ID Numbers: CM310NP001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No