A Study of CM326 in Patients With Chronic Rhinosinusitis With Nasal Polyps (DUBHE)

A Randomized, Double Blind, Placebo-controlled, Dose Escalation Phase 1b/2a Study to Evaluate the Safety, Tolerability, PK, PD, Immunogenicity and Preliminary Efficacy of CM326 in Patients With Chronic Rhinosinusitis With Nasal Polyps

This is a multi-center, randomized, double blind, placebo-controlled, dose escalation study to evaluate the safety, tolerability, PK, PD, immunogenicity and preliminary efficacy of CM326 in patients with chronic rhinosinusitis with nasal polyps.

Study Overview

• Status: Active, not recruiting
• Conditions: Chronic Rhinosinusitis With Nasal Polyps
• Intervention / Treatment: Other: Placebo; Drug: CM326

Detailed Description

The study consists of 3 periods, a Screening Period, a Treatment Period and a Safety Follow-up Period.

Subjects who meet eligibility criteria will be randomized to receive either CM326 or placebo subcutaneously.

• Study Type: Interventional
• Enrollment (Estimated): 113
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China
      • Beijing Tongren Hospital, CMU

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Subjects who are capable of understanding the nature of the study and voluntarily signing the ICF.
• Male or female subjects, aged between 18 and 70 years old (inclusive), with a body mass index (BMI) ≥ 19 kg/m2.
• Diagnosed with Chronic Rhinosinusitis With Nasal Polyps.
• The total NPS score should be at least 3 points, with at least 1 point in each side of the nasal cavity.
• Prior treatment with systemic corticosteroids (SCS) within two years before screening, and/or contraindicate to or intolerance to systemic corticosteroids, and/or with prior surgery to nasal polyps 6 months before the screening.
• Ongoing symptoms for at least 4 weeks before screening：1) Nasal congestion/obstruction; 2) Other symptom, e.g., loss of smell or rhinorrhea.

Exclusion Criteria:

• Allergic or intolerant to mometasone furoate spray or CM326/placebo.
• Have used of systemic immunosuppressants for inflammatory or autoimmune diseases within 8 weeks or 5 half-lives prior to randomization.
• Have initiated leukotriene receptor antagonist therapy within 4 weeks prior to randomization.
• have received allergen-specific immunotherapy that initiated within 3 months prior to randomization or planned to be initiated during the study period.
• Have undergone nasal surgery (including nasal polypectomy) within 6 months prior to screening.
• Have received medium- and short-acting systemic corticosteroids (including oral, intravenous, intramuscular corticosteroids), nasal dripping corticosteroids, traditional Chinese medicine (including systemic and local herbal products preparations) for chronic rhinosinusitis (CRS) within 4 weeks prior to screening, or long-acting systemic corticosteroids.
• With concomitant asthma (including suspected diagnosis of asthma) will be excluded if they meet the following conditions: predicted FEV1 of≤ 60%, or acute exacerbation of asthma within 3 months prior to screening requiring SCS or hospitalization (> 24 hours), or using inhaled corticosteroids (ICS) of > 1000 μg fluticasone propionate or others at equivalent doses
• With antrochoanal polyps.
• With severe deviation of the nasal septum occludes at least one nostril.
• With persistent rhinitis medicamentosas.
• With allergic granulomatous angiitis (Churg-Strauss syndrome), granulomatosis with polyangiitis (Wegener's granulomatosis), Young's syndrome, Kartagener's syndrome or other dyskinetic ciliary syndromes, cystic fibrosis.
• With acute sinusitis, nasal infection, or upper respiratory tract infection at screening.
• Have symptoms or whose CT scan suggests allergic fungal sinusitis.
• With malignant or benign neoplasm of nasal cavities.
• With other uncontrolled serious diseases or recurrent chronic diseases.
• Have severe hepatic and renal impairment.
• Have received live attenuated vaccines within 12 weeks prior to randomization, or during the planned study; or have received inactivated vaccines (e.g., novel coronavirus vaccines) within 30 days prior to randomization.
• With known or suspected immunosuppression, including, but not limited to, the history of invasive opportunistic infections.
• Subjects who are pregnant or planning to become pregnant, or breastfeeding during the study.
• With a history of large alcohol consumption or a history of drug abuse within 3 months prior to screening.
• With other medical or non-medical conditions that are not suitable for participation in the study in the opinion of the investigator.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1: 55mg Q2W; CM326 55 mg or matched placebo, every 2 weeks, subcutaneous (SC)	Other: Placebo; Placebo; Drug: CM326; CM326 injection
Experimental: Group 2: 110mg Q2W; CM326 110 mg or matched placebo, every 2 weeks, subcutaneous (SC)	Other: Placebo; Placebo; Drug: CM326; CM326 injection
Experimental: Group 3: 220mg Q2W; CM326 220 mg or matched placebo, every 2 weeks, subcutaneous (SC)	Other: Placebo; Placebo; Drug: CM326; CM326 injection
Experimental: Group 4: 220mg Q4W; CM326 220mg or matched placebo, every 4 weeks, subcutaneous (SC)	Other: Placebo; Placebo; Drug: CM326; CM326 injection
Experimental: Group 5: CM326 220 mg Q2W; CM326 220 mg, every 2 weeks, subcutaneous (SC)	Drug: CM326; CM326 injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of AEs, including any abnormal physical examinations, abnormal vital signs, abnormal ECG, and abnormal lab testing.	Incidence of AEs, including any abnormal physical examinations, abnormal vital signs, abnormal ECG, and abnormal lab testing.	up to Week 64
Changes from baseline of nasal polyp score (NPS) in eosinophilic chronic rhinosinusitis with nasal polyps (CRSwNP) at week 16.	NPS score ranges from 0-8. (sum of 0-4 for each nasal passage scores), higher score means a worse outcome.	at week 16

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PK: Concentration of CM326 in plasma	Concentration of CM326 in plasma	up to Week 64
Immunogenicity: anti-drug antibody (ADA)	Occurrence of positive anti-drug antibody (ADA)	up to Week 64
PD: Changes from baseline in serum thymus activation regulation chemokine (TARC) concentration after CM326 administration.	Changes from baseline in serum thymus activation regulation chemokine (TARC) concentration after CM326 administration.	up to Week 64
PD: Changes from baseline in serum total immunoglobulin E (IgE) concentration after CM326 administration.	Changes from baseline in serum total immunoglobulin E (IgE) concentration after CM326 administration.	up to Week 64
PD: Changes from baseline in plasma interleukin-5 (IL-5) after CM326 administration	Changes from baseline in plasma interleukin-5 (IL-5) after CM326 administration	up to Week 64
PD: Changes from baseline in plasma interleukin-13 (IL-13) after CM326 administration	Changes from baseline in plasma interleukin-13 (IL-13) after CM326 administration	up to Week 64
PD: Changes from baseline in serum periostin after CM326 administration	Changes from baseline in serum periostin after CM326 administration	up to Week 64
PD: Changes from baseline in blood eosinophilic level after CM326 administration	Changes from baseline in blood eosinophil level after CM326 administration	up to Week 64
PD: Changes from baseline in eosinophilic level of nasal polyp biopsy tissue after CM326 administration	Changes from baseline in eosinophil level of Nasal polyp biopsy tissue after CM326 administration	up to Week 64
Efficacy: changes from baseline of nasal polyp score (NPS) in non-eosinophilic chronic rhinosinusitis with nasal polyps (CRSwNP)	NPS score ranges from 0-8. (sum of 0-4 for each nasal passage scores), higher score means a worse outcome.	up to Week 64

Collaborators and Investigators

• Sponsor: Keymed Biosciences Co.Ltd
• Investigators: Principal Investigator: Luo Zhang, Beijing Tong-Ren hospital

Study record dates

Study Major Dates

• Study Start (Actual): July 11, 2022
• Primary Completion (Estimated): August 29, 2023
• Study Completion (Estimated): August 30, 2024

Study Registration Dates

• First Submitted: March 18, 2022
• First Submitted That Met QC Criteria: April 5, 2022
• First Posted (Actual): April 12, 2022

Study Record Updates

• Last Update Posted (Actual): August 4, 2023
• Last Update Submitted That Met QC Criteria: August 2, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• 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: CM326NP001

Drug and device information, study documents

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