A Extension Clinical Study of TQC2731 Injection in the Treatment of Chronic Sinusitis With Nasal Polyps

A Multicenter, Randomized, Ongoing Trial Evaluating the Long-term Safety and Efficacy of TQC2731 Injection in the Treatment of Chronic Sinusitis With Nasal Polyps

This study aims to evaluate the efficacy and safety of TQC2731 injection in the treatment of chronic sinusitis with nasal polyps.

Inclusion Criteria:

• Subjects sign informed consent before study, fully understand the purpose, procedures and possible adverse reactions of the study;
• Male and female, ≥18 years old;
• Participate in the clinical study of TQC2731 for the treatment of chronic rhinosinusitis with nasal polyps (CRSwNP) (study number TQC2731-II-02) and meet the following criteria "a" or "b": a. Participants complete the prescribed treatment according to the protocol requirements and complete end of treatment (EOT) visits; b. The subject withdrew early due to poor compliance or other objective reasons other than TQC2731 related adverse events (AEs), and completed the early withdrawal visit according to the plan. After evaluation by the researcher and sponsor, the factors that led to the subject's early termination of the main study treatment have disappeared/no longer affect the subject's participation in this continuing study;
• Subjects used steady dose of intranasal glucocorticoids (INCS) over 4 weeks before screening (subjects willing to use Mometasone Furoate Aqueous Nasal Spray (MFNS) while studying);
• Subjects agree from sign informed consent to last administration over 6 mouth without Family planning，and take effective non-pharmaceutical contraception.

Exclusion Criteria:

• In the main study (TQC2731-II-02), SAE related to TQC2731 occurred, or TQC2731 treatment was terminated due to AE related to TQC2731. After discussion between the investigator and the sponsor, it was determined that the subject was not suitable to continue receiving TQC2731 treatment;

• The subjects had poor compliance in the main study and were deemed unable to complete this continuing study by the researchers;

• During the main study (TQC2731-II-02), any serious progression or poorly controlled comorbidities were found (such as asthma exacerbation requiring adjustment of background medication), and the main investigator determined that the subject was not suitable to participate in the trial;

• Presence of conditions/concomitant diseases that affect the evaluation of efficacy, e.g.

  1. Posterior nostril polyps;
  2. Imaging suspected or confirmed fungal sinusitis;
  3. Nasal polyp score(NPS) cannot be evaluated due to nasal surgery to alter the structure of the lateral nasal wall;
  4. Subjects with nasal malignancies and benign tumors (papilloma, blood furuncle, etc.).

• Any type of active malignancy or a history of malignancy (Patient with basal cell carcinoma, skin localized squamous cell carcinoma or carcinoma in situ of cervix, if curative treatment was completed for more than 12 months prior to visit 1 can join the study; Other malignant tumors can join the study if patients had completed curative therapy for at least 5 years prior to visit 1);

• Active autoimmune disease;

• Known or suspected history of immunosuppression, immune dysfunction, or immune dysfunction, including but not limited to invasive opportunistic infections, even if the infection has subsided;

• Uncontrolled epistaxis occurred within 2 months before screening;

• Infection requiring treatment with systemic antibacterial, antiviral, antifungal, antiparasitic, or antiparasitic agents occurred within 14 days before screening;

• Helminth parasite infection was diagnosed within 24 weeks prior to screening and had not received or failed to respond to standard treatment;

• Leukotriene antagonists/modulators were used while screening(using a stable dose of leukotriene modulator for ≥30 days before screening was accepted);

• Regular use of decongestants (topical or systemic) before screening, short-term use for endoscopy excepted;

• Patients who received any of the following treatments before screening:

  1. Immunosuppressive therapy had been administered within the previous 8 weeks or five half-lives (whichever was longer), (including but not limited to cyclophosphamide, cyclosporine, interferon-γ, azathioprine, methotrexate, mycophenolate mofetil and tacrolimus, etc.);
  2. Monoclonal antibody therapy had been administered within the previous 8 weeks or five half-lives (whichever was longer), (Including but not limited to: benralizumab, mepolizumab, omalizumab, resveratrol, dupilumab, etc.);
  3. Systemic glucocorticoids were used during the first 28 days;
  4. Glucocorticoid-eluting nasal stents were used during the first 6 mouths;
  5. Immune globulin or blood products therapy were used during the first 28 days; 6）Live attenuated vaccine was administered for the first 28 days or during the planned study period; 7）Received allergen specific immunotherapy 6 mouth before screening(if being treated at a stable dose and not expected to change during study,3 mouth before screening and 1 mouth before visit 1 were accepted); 8）Join any other study within 3 mouths.

• Patients with concomitant asthma begin inhaled corticosteroid therapy within the first 4 weeks of the screening period (For patients who have been assessed to maintain a stable dose for at least 4 weeks prior to screening and whose dose has been maintained throughout the entire study period, inhaled corticosteroids can be administered at a dose of ≤ 1000μ Fluticasone propionate or equivalent doses of other inhaled corticosteroids.);

• Any infectious disease screening indicator that meets the following criteria during screening:

  1. Active tuberculosis infection during screening;
  2. Hepatitis B virus surface antigen (HBsAg) positive, or hepatitis B core antibody (HBcAb) positive and hepatitis B virus (HBV) DNA positive;
  3. Anti-hepatitis C virus (Anti-HCV) positive and Hepatitis C virus ribonucleic acid (HCV-RNA) positive;
  4. Positive Treponema pallidum antibody (Anti TP) (if the Treponema pallidum serological test is positive, further non treponema pallidum serological tests will be conducted, the latter being negative and judged by the researcher as a patient who has previously been infected with syphilis but has been cured and meets the inclusion criteria);
  5. Positive for human immunodeficiency virus antibodies (Anti HIV);

• Abnormal laboratory test results:

  1. Aspartate aminotransferase (AST)>2.5 x upper limit of normal value (ULN);
  2. Alanine aminotransferase (ALT)>2.5 x upper limit of normal value (ULN);
  3. Creatinine>1.5 x ULN.

• Pregnant or lactating women;

• A history of or allergic reaction to Mometasone furoate nasal spray (Nasonex ®) or any component of TQC2731 injection;

• A history of systemic allergy to any biologic drug(except local injection site reactions);

• The subjects had poor compliance and were judged unable to complete the study;

• Any clinically significant abnormal findings, including physical examination, vital signs, 12-lead electrocardiogram, blood biochemistry, blood routine or urine routine, and the researcher's judgment that participating in the trial may put the patient at risk, or may affect the study results or hinder the patient's ability to complete the entire study process.