Clinical trial NCT05324137: A Study of CM326 in Patients With Chronic Rhinosinusitis With Nasal Polyps
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Chronic Rhinosinusitis With Nasal Polyps
Lead sponsor: Keymed Biosciences Co.Ltd
Sponsor class: INDUSTRY
First posted: 2022-04-12
Enrollment: 88
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Incidence of AEs, including any abnormal physical examinations, abnormal vital signs, abnormal ECG, and abnormal lab testing.
timeFrame: up to Week 64
measure: Changes from baseline of nasal polyp score (NPS) in eosinophilic chronic rhinosinusitis with nasal polyps (CRSwNP) at week 16.
timeFrame: at week 16
Secondary outcomes:
measure: PK: Concentration of CM326 in plasma
timeFrame: up to Week 64
measure: Immunogenicity: anti-drug antibody (ADA)
timeFrame: up to Week 64
measure: PD: Changes from baseline in serum thymus activation regulation chemokine (TARC) concentration after CM326 administration.
timeFrame: up to Week 64
measure: PD: Changes from baseline in serum total immunoglobulin E (IgE) concentration after CM326 administration.
timeFrame: up to Week 64
measure: PD: Changes from baseline in plasma interleukin-5 (IL-5) after CM326 administration
timeFrame: up to Week 64
measure: PD: Changes from baseline in plasma interleukin-13 (IL-13) after CM326 administration
timeFrame: up to Week 64
measure: PD: Changes from baseline in serum periostin after CM326 administration
timeFrame: up to Week 64
measure: PD: Changes from baseline in blood eosinophilic level after CM326 administration
timeFrame: up to Week 64
measure: PD: Changes from baseline in eosinophilic level of nasal polyp biopsy tissue after CM326 administration
timeFrame: up to Week 64
measure: Efficacy: changes from baseline of nasal polyp score (NPS) in non-eosinophilic chronic rhinosinusitis with nasal polyps (CRSwNP)
timeFrame: up to Week 64
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Tongren Hospital, CMU
state: Beijing
Study officials:
affiliation: Beijing Tong-Ren hospital
name: Luo Zhang
role: PRINCIPAL_INVESTIGATOR
References: