Clinical Trial of TQC2731 Injection in Patients With Chronic Sinusitis and Nasal Polyps

A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Phase III Clinical Trial to Evaluate the Efficacy and Safety of TQC2731 Injection in Patients With Chronic Rhinosinusitis With Nasal Polyps (CRSwNP)

TQC2731 injection is a humanized monoclonal antibody that targets Thymic Stromal Lymphopoietin (TSLP), blocks the TSLP pathway, and inhibits the production of downstream cytokines, thereby exerting anti-inflammatory effects. The purpose of this study is to evaluate the efficacy and safety of TQC2731 injection in patients with chronic rhinosinusitis with nasal polyps (CRSwNP).

Inclusion Criteria:

• Signed informed consent form prior to trial participation, demonstrating full understanding of trial objectives, procedures, and potential adverse reactions.
• Age between 18 and 75 years (inclusive) at the time of informed consent signing, regardless of gender.
• Diagnosis of bilateral chronic rhinosinusitis with nasal polyps (CRSwNP) meeting the diagnostic criteria of the "Chinese Guidelines for the Diagnosis and Treatment of Chronic Rhinosinusitis (2018)"
• At least one prior course of systemic corticosteroids (prednisone 0.5-1 mg/kg/day or 15-30 mg/day or equivalent for minimum 5 days) within 2 years before screening, with persistent bilateral CRSwNP; AND/OR contraindication/intolerance to systemic corticosteroids; AND/OR prior nasal polyp surgery performed more than 6 months before screening.
• Bilateral Nasal Polyp Score (NPS) ≥5 (maximum score 8) with ≥2 points per nostril, as assessed by nasal endoscopy during screening and randomization.
• Nasal Congestion Score (NCS) ≥2 at screening (daily average) and randomization (weekly average).
• Persistent symptoms of rhinorrhea and/or hyposmia/anosmia for over 8 weeks prior to screening.
• 22-item Sino-Nasal Outcome Test (SNOT-22) score ≥30 at screening and randomization.
• Stable dose of intranasal corticosteroids (INCS) for >4 weeks prior to screening (subjects using non-mometasone furoate nasal spray [MFNS] products must agree to switch to Mometasone Furoate Nasal Spray (MFNS) during the study).
• Subjects with comorbid asthma must have had stable asthma symptoms for ≥4 weeks prior to screening (if using medications, such as inhaled corticosteroids, the same dose must have been stably maintained for ≥4 weeks before screening, and the dose is assessed to remain stable during the first phase).
• The evaluation during the lead-in period showed that the medication adherence to intranasal mometasone furoate nasal spray (MFNS) was greater than 70%, and the adherence to daily symptom assessment records in the subjects' electronic logs was also greater than 70%. Note: Days with missing electronic log data were considered non-adherent to this criterion.
• Agreement to practice effective non-pharmacologic contraception from informed consent until 6 months post-final dose, for subjects/partners of childbearing potential.

Exclusion Criteria:

• Conditions/Diseases Affecting Efficacy Evaluation

  • Nasal septum deviation causing ≥1 nostril obstruction；
  • Perforation of the nasal septum
  • Acute sinusitis, nasal infection, or upper respiratory infection within 2 weeks pre-screening or during screening/run-in periods；
  • Rhinitis medicamentosa；
  • Eosinophilic granulomatosis with polyangiitis (EGPA), granulomatosis with polyangiitis (GPA), Young's syndrome, Kartagener's syndrome, other ciliary dyskinesia syndromes, or cystic fibrosis；
  • Suspected or confirmed fungal sinusitis by imaging；
  • Prior nasal surgery altering lateral wall structure precluding NPS assessment；
  • Nasal malignancies or benign tumors (e.g., papilloma, hemangioma)；

• Any intranasal and/or sinus surgery (including polypectomy) within 6 months prior to screening.

• Uncontrolled epistaxis within 2 months prior to screening.

• Regular use of decongestants (topical or systemic) prior to screening, except for short-term use during endoscopic examinations.

• Patients who have received any of the following treatments prior to randomization:

  • Treatment with immunosuppressants (including but not limited to: cyclophosphamide, cyclosporine, interferon gamma, azathioprine, methotrexate, mycophenolate, tacrolimus, Secukinumab) within 8 weeks or 5 half-lives prior to screening (whichever is longer)；
  • Treatment with any monoclonal antibodies (including but not limited to: benralizumab, mepolizumab, omalizumab, dupilumab, or other similar drugs [e.g., TSLP blockers]) within 8 weeks or 5 half-lives prior to screening (whichever is longer).
  • Patients who used medium- or short-acting systemic corticosteroids (SCS, including oral, intravenous, or intramuscular administration), systemic traditional Chinese medicine preparations for treating CRS within 4 weeks prior to screening, or received long-acting SCS (e.g., triamcinolone acetonide injection) within 6 weeks prior to screening, or who plan to receive the aforementioned medications during the study period.
  • Use of corticosteroid-eluting nasal stents within 6 months prior to screening;
  • Treatment with immunoglobulins or blood products within 28 days prior to screening;
  • Administration of live attenuated vaccines within 28 days prior to screening or planned during the study period;
  • Allergen-specific immunotherapy within 6 months prior to screening (allowed only if: initiated >3 months before screening, maintained at a stable dose for ≥1 month before Visit 1, and no planned dose changes during the study)；
  • Participation in other drug/medical device clinical trials within 3 months prior to screening (based on last administration/use).
  • Use nasal antihistamines (such as olopatadine nasal spray, azelastine nasal spray, levocabastine nasal spray, etc.) for the first 3 days.

• Screening for a history of active pulmonary tuberculosis within the past 12 months；

• Exclusion of infections within the last 14 days requiring systemic antibiotic, antiviral, antifungal, antiparasitic, or antiprotozoal therapy;

• Exclusion of subjects diagnosed with helminthic parasitic infection in the past 6 months who either did not receive standard treatment or had treatment failure；

• Known or suspected history of immunosuppression, immune dysfunction, or immune dysregulation, including but not limited to invasive opportunistic infections (histoplasmosis, listeriosis, coccidioidomycosis, pneumocystosis, aspergillosis), even if the infection has resolved; Or there is an unusual frequency, recurrence, or prolonged infection (as judged by the investigator).

• The forced expiratory volume in the first second (FEV1) of the subjects during the screening/introduction period was ≤ 50% of the normal predicted value.

• Patients with comorbid asthma who meet any of the following criteria:

Asthma exacerbation within 90 days before screening, or current use of inhaled corticosteroids (ICS) at a daily dose higher than 1000μg fluticasone (or equivalent).

Definition of Asthma Acute Exacerbation:

• Use of systemic corticosteroids (or a temporary increase in the stable dose of baseline OCS) for at least 3 consecutive days due to worsening asthma; a single injection of depot long-acting corticosteroids may be considered equivalent to a 3-day course of systemic corticosteroids.

• An emergency department or urgent care center visit due to asthma requiring systemic corticosteroids (as described above) (defined as evaluation and treatment in the emergency department or urgent care center lasting <24 hours).

• Hospitalization due to asthma (defined as admission to a medical facility and/or evaluation and treatment in a healthcare setting lasting ≥24 hours).

  • Use of leukotriene antagonists/modulators prior to randomization (subjects who have been on a stable dose of leukotriene modulators for ≥30 days continuously prior to randomization may be enrolled);
  • Presence of other concurrent active or clinically significant respiratory diseases that, in the investigator's judgment, may significantly impact the study, such as active tuberculosis, lung cancer, bronchiectasis, pulmonary sarcoidosis, pulmonary fibrosis, pulmonary hypertension, interstitial lung disease, or other active pulmonary conditions
  • Subjects who have undergone lobectomy or lung volume reduction surgery within 12 months prior to the start of the study;
  • Exclusion of subjects with cardiovascular conditions (including but not limited to unstable ischemic heart disease, heart failure, uncontrolled hypertension, myocardial infarction, significant arrhythmias, long QT syndrome, or Fridericia-corrected QT interval (QTcF) prolongation [≥450 ms in men, ≥470 ms in women]) if the investigator deems participation could compromise safety or study outcome interpretation;
  • Exclude individuals with difficult venous access or a history of vasovagal syncope (needle/blood-related);
  • Exclusion of any current active malignancy or history of malignancy (Patients with basal cell carcinoma, localized squamous cell carcinoma of the skin, or carcinoma in situ of the cervix are eligible if curative treatment was completed >12 months before V1. Patients with other malignancies are eligible if curative treatment was completed at least 5 years before V1).
  • Presence of active autoimmune diseases (including but not limited to Hashimoto's thyroiditis with hyperthyroidism, Graves' disease, inflammatory bowel disease, primary biliary cholangitis, systemic lupus erythematosus, multiple sclerosis and other neuroinflammatory disorders, psoriasis vulgaris, and rheumatoid arthritis);
  • Exclusion if any infectious disease screening indicator meets the following criteria during screening;

• Exclusion of subjects who are positive for hepatitis B virus surface antigen (HBsAg).

• Hepatitis B virus core antibody (HBcAb) with detectable Hepatitis B Virus (HBV)-DNA.

• Exclude if Hepatitis C Virus (HCV) antibody-positive and HCV-RNA positive, or if previously treated for HCV (regardless of current HCV-RNA status).

• Anti-Treponema pallidum antibody (Anti-TP) positive (if syphilis serology is positive, a non-treponemal test must be performed; subjects with a negative non-treponemal test and deemed by the investigator as previously cured are eligible).

• Anti-HIV positive

  • Abnormal laboratory test results:

• White blood cell count <3.5 × 10⁹/L;

• Aspartate aminotransferase (AST) >2.5 × upper limit of normal (ULN);

• Alanine aminotransferase (ALT) >2.5 × ULN;

• Total bilirubin >2 × ULN;

• Creatinine >1.5 × ULN

  • Any clinically significant abnormal findings during the import period, including physical examination, vital signs, 12-lead ECG, blood biochemistry, hematology, or urinalysis, which in the investigator's judgment may place the patient at risk, affect study results, or impair the patient's ability to complete the entire study
  • Women who are pregnant or lactating.
  • Those who were still smokers or had quit smoking for less than six months at the time of screening.
  • Exclude those with regular excessive alcohol consumption (>14 units/week for females or >21 units/week for males) in the past 6 months, inability to abstain during the trial, or a positive breath alcohol test.
  • History of drug abuse within the past 2 years, or a positive drug abuse screening result.
  • Subjects with a known history of hypersensitivity or allergic reaction to any ingredient of mometasone furoate nasal spray (Nasonex®) or TQC2731 injection.
  • Exclusion for any history of systemic allergic reaction to biologic agents (local injection site reactions excluded).
  • The participant demonstrated poor adherence and was deemed unable to complete the study.
  • Any medical or psychiatric condition that, in the judgment of the investigator or the sponsor's medical reviewer, may affect the subject's safety throughout the study or impede the subject's ability to complete the entire study process or interfere with the interpretation of study results, including but not limited to cardiovascular, gastrointestinal, hepatic, renal, neurological, musculoskeletal, infectious, endocrine, metabolic, hematologic disorders, psychiatric illnesses, or major physical disabilities.