Subcutaneously CM310/Placebo in Patients With Chronic Rhinosinusitis With Nasal Polyposis (CRSwNP)

• ClinicalTrials.gov Identifier: NCT04805398
• Recruitment Status: Active, not recruiting
• First Posted: March 18, 2021
• Last Update Posted: November 11, 2021
• Sponsor: Keymed Biosciences Co.Ltd
• Information provided by (Responsible Party): Keymed Biosciences Co.Ltd

Study Description

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).

Condition or disease	Intervention/treatment	Phase
Chronic Rhinosinusitis (Diagnosis); Nasal Polyps	Biological: CM310; Biological: Placebo	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 56 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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)
• Actual Study Start Date: April 1, 2021
• Estimated Primary Completion Date: March 2022
• Estimated Study Completion Date: June 2022

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Bilateral endoscopic Nasal Polyps Score (NPS) [ Time Frame: 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.
2. Nasal Congestion/Obstruction SymptomSeverity (NCS) Score [ Time Frame: at Week 16 ]
   Change from baseline in the NCS score. NCS score (0-3), higher score means worse nasal symptom.

Secondary Outcome Measures :

1. Time to the first response of NPS [ Time Frame: Baseline up to Week 24 ]
   Time to the first response of NPS (defined as bilateral endoscopic NPS improved ≥1).
2. Lund-Mackay score [ Time Frame: 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.
3. Volume of the involved area of nasosinusitis on 3D-construction CT scan [ Time Frame: at Week 16 ]
   Change from baseline in the volume of the involved area of nasosinusitis on 3D-construction CT scan.
4. Bilateral endoscopic NPS [ Time Frame: at Week 8 ]
   Change from baseline in the bilateral endoscopic NPS.
5. Proportion of subjects receiving rescue therapy for nasal polyps [ Time Frame: Baseline up to Week 24 ]
   Proportion of subjects receiving rescue therapy for nasal polyps.
6. University of Pennsylvania Smell Identification Test (UPSIT) [ Time Frame: at Week 16 ]
   Change from baseline in UPSIT. UPSIT score (0-40). Higher score means better sense of smell.
7. 22-item Sino-nasal Outcome Test Scores(SNOT-22) score [ Time Frame: at Week 16 ]
   Change from baseline in SNOT-22 score. SNOT-22 score (0-110). Higher score means a worse outcome.
8. Total Symptom Score(TSS) score [ Time Frame: at Week 16 ]
   Change from baseline in TSS score. TSS score (0-9). Higher score means worse nasal symptom.
9. Bilateral endoscopic NPS [ Time Frame: at Week 16 ]
   Change from baseline in the bilateral endoscopic NPS in subjects with concurrent asthma.
10. Bilateral endoscopic NCS [ Time Frame: at Week 16 ]
    Change from baseline in the NCS in subjects with concurrent asthma.
11. Safety parameters [ Time Frame: Baseline up to Week 24 ]
    Incidence of treatment-emergent adverse events (TEAEs), of treatment-emergent serious AEs (TESAEs), etc.
12. Pharmacokinetics(PK) [ Time Frame: Baseline up to Week 24 ]
    Trough concentration and exposure.
13. Pharmacodynamics(PD) [ Time Frame: Baseline up to Week 24 ]
    Change from baseline in serum biomarker level (TARC, total IgE and eosinophil level).
14. PD(eosinophil level in nasal polyps biospy tissue) [ Time Frame: at Week 16 ]
    Change from baseline of eosinophil level in nasal polyps biospy tissue.
15. Anti-drug antibodies(ADA) [ Time Frame: Baseline up to Week 24 ]
    Incidence of ADA.
16. Neutralizing antibody (Nab) [ Time Frame: Baseline up to Week 24 ]
    Incidence of Nab.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 70 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

China, Beijing

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

China, Chongqing

First Affiliated Hospital of Chongqing Medical University

Chongqing, Chongqing, China

China, Hubei

Jingzhou Central Hospital

Jingzhou, Hubei, 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

China, Hunan

Third Xiangya Hospital of Central South University

Changsha, Hunan, China

China, Jiangxi

The First Affiliated Hospital of Nanchang University

Nanchang, Jiangxi, China

China, Shandong

Affiliated Hospital of Qingdao University

Qingdao, Shandong, China

Yantai Yuhuangding Hospital

Yantai, Shandong, China

China, Shangdong

Shandong Second Provincial General Hospital (Shandong ENT hospital)

Jinan, Shangdong, China

China, Shanghai

Renji Hospital of Shanghai Jiaotong University School of Medicine

Shanghai, Shanghai, China

Tongji Hospital of Tongji University

Shanghai, Shanghai, China

China, Shanxi

Second Hospital of Shanxi Medical University

Taiyuan, Shanxi, China

China, Sichuan

Hospital of Chengdu University of Traditional Chinese Medicine

Chengdu, Sichuan, China

West China Hospital of Sichuan University

Chengdu, Sichuan, China

China, Zhejiang

Zhejiang Provincial People's Hospital

Hangzhou, Zhejiang, China

Sponsors and Collaborators

Keymed Biosciences Co.Ltd

Investigators

• Principal Investigator: Luo Zhang; Beijing Tongren Hospital, CMU

More Information

• Responsible Party: Keymed Biosciences Co.Ltd
• ClinicalTrials.gov Identifier: NCT04805398
• Other Study ID Numbers: CM310NP001
• First Posted: March 18, 2021
• Last Update Posted: November 11, 2021
• Last Verified: November 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Keymed Biosciences Co.Ltd:

Chronic Rhinosinusitis with Nasal Polyps

Additional relevant MeSH terms:

Sinusitis; Nasal Polyps; Polyps; Pathological Conditions, Anatomical; Respiratory Tract Infections; Infections; Paranasal Sinus Diseases; Nose Diseases; Respiratory Tract Diseases; Otorhinolaryngologic Diseases