A Clinical Study of TQC2731 Injection in the Treatment of Chronic Rhinosinusitis 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 and ≤ 75 years old;

• Bilateral chronic rhinosinusitis with nasal polyps (CRSwNP) who met the diagnosticcriteria of the Chinese Guidelines for the Diagnosis and Treatment of chronicrhinosinusitis (2018);

• Received nasal polyp surgery or received systemic glucocorticoid treatment 2 yearsbefore screening;

• Bilateral nasal polyp score (NPS) ≥5 and each nostril was scored ≥ 2 when screeningand randomization;

• Nasal congestion score (NCS) ≥2 when screening and randomization;

• Persistent nasal leakage or smell decrease or loss last more than 8 weeks beforescreening;

• Sinonasal outcome testing 22 (SNOT-22) score ≥ 30 when screening and randomization;

• Subjects received steady dose of intranasal glucocorticoids (INCS) over 4 weeksbefore screening (subjects agree use Mometasone Furoate Aqueous Nasal Spray (MFNS)while studying);

• Subjects with asthma start inhaled stable dose of glucocorticoid therapy over 4weeks before screening, and are willing to keep the dose during whole study;

• MFNS medication compliance ≥70%, subjects daily symptom assessment compliance ≥70%through Patient dairy;

• Subjects agree to take effective non-pharmaceutical contraception from signinginformed consent to 6 mouth after last administration.

Exclusion Criteria:

• Presence of conditions/concomitant diseases that affect the evaluation of efficacy,such as:

1. Posterior nostril polyps;

2. Deviation of the nasal septum resulted in obstruction of at least one nostril;

3. Acute sinusitis, nasal infection, or upper respiratory tract infection hadoccurred 2 weeks before screening, screening period or mediation period;

4. Drug induced rhinitis;

5. Allergic granulomatous vasculitis (Churg-Strauss syndrome), granuloma with polyvasculitis (Wegener's granuloma), Young syndrome, Kartagener syndrome, or otherdysphoric ciliary syndrome, with cystic fibrosis;

6. Imaging suspected or confirmed fungal sinusitis;

7. NPS cannot be evaluated due to nasal surgery to alter the structure of thelateral nasal wall;

8. Subjects with nasal malignancies and benign tumors (papilloma, blood furuncle,etc.)

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

• Active autoimmune disease (including but not limited to Hashimoto's thyroiditis,Graves disease, Inflammatory bowel disease, Primary biliary cholangitis, Systemiclupus erythematosus, Multiple sclerosis and other neuroinflammatory diseases,Psoriasis vulgaris, Rheumatoid arthritis);

• Known or suspected history of immunosuppression, immune disorders, or immunedisorders, including but not limited to invasive opportunistic infections (histoplasmosis, listeriosis, coccidioides, pulmonary cysticercosis disease,aspergillosis), even if the infection has been resolved;

• Any intranasal and/or sinus surgery (including polypectomy) within 6 months beforescreening;

• Uncontrolled epistaxis occurred within 2 months before screening;

• A history of active pulmonary tuberculosis in the 12 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 hadnot received or failed to respond to standard treatment;

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

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

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

1. Received immunosuppressive therapy within the previous 8 weeks or fivehalf-lives (whichever was longer), (including but not limited tocyclophosphamide, cyclosporine, interferon-γ, azathioprine, methotrexate,mycophenolate mofetil and tacrolimus, etc.);

2. Received monoclonal antibody therapy within the previous 8 weeks or fivehalf-lives (whichever was longer), (Including but not limited to: benralizumab,mepolizumab, omalizumab, resveratrol, dupilumab, etc.);

3. Received systemic glucocorticoids within 28 days before the study;

4. Glucocorticoid-eluting nasal stents were used within 6 months before the study;

5. Immune globulin or blood products therapy were used within 28 days before thestudy;

6. Received or planned to receive live attenuated vaccine within 28 days before orduring the study period;

7. Received allergen specific immunotherapy 6 mouth before screening (if startedat 3 mouth before screening, being treated at a stable dose in 1 mouth beforevisit 1 and not expected to change during study, it would be acceptable);

8. Join any other clinical trials within 3 months;

• Patients with concurrent asthma had any of the following conditions: forcedexpiratory volume in the first second (FEV1) ≤ 50% of the expected normal value, oracute exacerbation of asthma within 90 days prior to screening, requiringhospitalization (>24 hours), or taking a daily dose greater than 1000 μg offluticasone or equivalent inhaled glucocorticoids (ICS);

• Hepatitis B surface Antigen (HBsAg) positive, or Hepatitis B core antibody (HBcAb)positive and Hepatitis B virus deoxyribonucleic acid (HBV-DNA) positive, oranti-hepatitis C virus (Anti-HCV) positive and Hepatitis C virus ribonucleic acid (HCV-RNA) positive, or anti-human Immunodeficiency Virus (Anti-HIV) positive, oranti-treponema pallidum (Anti-TP) positive;

• Any clinically significant abnormal findings, include physical examination, vitalsigns, 12-lead electrocardiogram, blood biochemistry, blood routine or urineroutine, and investigator judged that participating in the trial may put the patientat risk, or may affect the study outcome or hinder the patient's ability to completethe entire study process;

• Lab tests results were abnormal:

1. White cell count<3.5 x 10^9/L;

2. Aspartate aminotransferase (AST) > 2.5 x upper limits of normal (ULN);

3. Alanine aminotransferase (ALT) > 2.5 x ULN;

4. Total bilirubin > 2 x ULN;

5. Creatine phosphokinase (CPK)> 2 x ULN;

6. Creatinine >1.5 x ULN

• Pregnant or lactating women;

• A allergic history 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 sitereactions);

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

• Any medical or psychiatric disorder that was considered by the investigator or thesponsor medical reviewer to be likely to affect the safety of the subjectsthroughout the study or to prevent the subjects from completing the study orinterfere with the interpretation of the results; including but not limited tocardiovascular, gastrointestinal, liver, kidney, neurological, musculoskeletal,infectious, endocrine, metabolic, hematological diseases, psychiatric or major limbdisorders etc.