Long-term Safety and Efficacy of TQH2722 Injection in the Treatment of Chronic Sinusitis With or Without Nasal Polyps

A Multicenter, Randomized, Continuing Trial to Evaluate the Long-term Safety and Efficacy of TQH2722 Injection in the Treatment of Chronic Sinusitis With or Without Nasal Polyps

This is a multicenter, randomized, continuing, Phase II expansion trial to evaluate the safety, efficacy, and immunogenicity of two doses of TQH2722 in the long-term treatment of severe chronic sinusitis with or without nasal polyps.

Inclusion Criteria:

1. Inclusion Criteria of Part A

   • Sign informed consent before the test to fully understand the purpose, process and possible adverse reactions of the test;

   • Age 18-75 years old (including the threshold), male or female;

   • Enroll in the clinical study of TQH2722 for chronic sinusitis with or without nasal polyps (study number TQH2722-II-02) and meet the following criteria "a" or "b" :

     1. Subjects completed prescribed treatment as required and completed Part A end of study (EOS) visit;
     2. The subjects withdrew early due to poor compliance or other objective reasons other than TQH2722-related AE, and completed the early exit interview according to the plan, and the influencing factors that led to the subjects' early termination of the main study treatment have disappeared/no longer affected the subjects' participation in the continuation study as assessed by the investigators and sponsors.

   Note: If protocol window period requirements are met, examination results from subject's main study EOS/ early exit visit may be used as screening/baseline examination for this study.

   • Subjects had used a more stable dose of nasal glucocorticoids (INCS) for more than 4 weeks prior to screening (for subjects who had used other INCS prior to screening than intranasal Mometasone furoate nasal spray (MFNS), subjects were willing to switch to MFNS during the study);
   • Subjects agree not to have a family plan for 6 months from the date of signing the informed consent to the last dose, and must use effective non-drug contraception with their sexual partners of childbearing age.

2. Inclusion Criteria of Part B

   • Sign informed consent before the test to fully understand the purpose, process and possible adverse reactions of the test;

   • Age 18-75 years old (including the threshold), male or female;

   • Enroll in the clinical study of TQH2722 for chronic sinusitis with or without nasal polyps (study number TQH2722-II-02) and meet the following criteria "a" or "b" :

     1. Subjects completed prescribed treatment as required and completed Part B EOS visit;
     2. The subjects withdrew early due to poor compliance or other objective reasons other than TQH2722-related AE, and completed the early exit interview according to the plan, and the influencing factors that led to the subjects' early termination of the main study treatment have disappeared/no longer affected the subjects' participation in the continuation study as assessed by the investigators and sponsors.

Note: If protocol window period requirements are met, examination results from subject's main study EOS/ early exit visit may be used as screening/baseline examination for this study.

• Subjects had used a more stable dose of nasal glucocorticoids (INCS) for more than 4 weeks prior to screening (for subjects who had used other INCS prior to screening than intranasal Mometasone furoate nasal spray (MFNS), subjects were willing to switch to MFNS during the study);
• Subjects agree not to have a family plan for 6 months from the date of signing the informed consent to the last dose, and must use effective non-drug contraception with their sexual partners of childbearing age.

Exclusion Criteria:

• In the main study (TQH2722-II-02), a TQH2722-related SAE occurred or TQH2722-related AE led to the discontinuation of TQH2722 therapy, and after discussion between the investigator and sponsor, the subject was deemed unsuitable for continuation of TQH2722 therapy.

• The subjects had poor compliance in the main study, and the researchers judged that they could not complete the continuing study.

• During the main study (TQH2722-II-02), any severe progression or poorly controlled concomitant disease (such as asthma exacerbation requiring adjustment of background medication) is identified and the subject is deemed unfit to participate by the principal investigator;

• Any of the following laboratory test values are abnormal during the screening period:

  1. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2.5 upper limit of normal (ULN);
  2. Total bilirubin > 2 x ULN (except indirect bilirubin elevation secondary to Gilbert syndrome);
  3. Creatinine > 1.5×ULN;

• Any medical condition, including but not limited to cardiovascular, gastrointestinal, liver, kidney, neurological, musculoskeletal, infectious, endocrine, metabolic, hematological, psychiatric, or major limb disorders, that the investigator believes is unstable and may affect the patient's safety throughout the study period, or affect the study results or their interpretation, or interfere with the patient's ability to complete the entire study process.For example, but not limited to: ischemic heart disease, left ventricular failure, arrhythmia, uncontrolled hypertension, uncontrolled hyperglycemia, cerebrovascular disease, etc.;

• Patients with active autoimmune diseases (including, but not limited to, Hashimoto thyroiditis, Graves' disease, inflammatory bowel disease, primary biliary cholangitis, systemic lupus erythematosus, multiple sclerosis and other neuroinflammatory diseases, psoriasis vulgaris, rheumatoid arthritis);

• Known or suspected immunosuppressed individuals, including but not limited to a history of invasive opportunistic infections (e.g., histoplasmosis, listeriosis, coccidioidomycosis, pulmonary cyst disease, aspergillosis), even if the infection has resolved;

• Subjects with active malignant tumors or a history of malignant tumors:Patients with basal cell carcinoma, skin localized squamous cell carcinoma, or cervical carcinoma in situ who had completed curative treatment for at least 12 months prior to visit 1 could be enrolled in this study; patients with other malignancies could be enrolled if they had completed curative treatment for at least 5 years prior to visit 1;

• A history of active pulmonary tuberculosis within 12 months prior to screening;

• Active hepatitis was present at the screening stage, either hepatitis B surface antigen (HBsAg) positive, hepatitis B core antibody (HBcAb) positive and Hepatitis B Virus-DNA positive, or Hepatitis C Virus (HCV) antibody positive and HCV-RNA positive; or human immunodeficiency virus (Anti-HIV) positive, or treponema pallidum antibody (Anti-TP) positive (if the treponema pallidum serological test is positive, then further non-treponema pallidum serological test is performed, the latter is negative and the investigator determines that patients who have been infected with syphilis in the past but have been cured are eligible for inclusion);

• Diagnosis of helminthic infection within 6 months prior to the screening period, failure to receive standard treatment or failure to respond to standard treatment;

• Subjects who received the following treatments:

  1. Had sinus surgery or nasal sinus surgery within 6 months prior to screening (visit 1).
  2. Received monoclonal antibody therapy within 8 weeks or 5 half-lives prior to screening (whichever is longer);
  3. Received immunosuppressive therapy (including but not limited to cyclophosphamide, cyclosporine, interferon gamma, azathioprine, methotrexate, mycophenolate and tacrolimus) within 8 weeks or 5 half-lives prior to screening, whichever is longer;
  4. Use of other non-biological agents within 8 weeks or 5 half-lives (whichever is longer) prior to screening;
  5. Intravenous immunoglobulin (IVIG) therapy and/or plasma exchange within 30 days prior to screening visit (Visit 1);
  6. Subjects treated with leukotriene antagonists/modulators prior to screening (subjects treated with stable doses of leukotriene modulators for ≥30 days prior to screening can be enrolled);
  7. Start allergen immunotherapy within 3 months prior to screening, or plan to start such therapy during the study period or plan to change the therapeutic dose during the study period;
  8. Have received live attenuated vaccine within 4 weeks prior to screening or plan to receive live attenuated vaccine during the study period;
  9. Chronic active or acute infection requiring systemic treatment with antibiotics, antivirals, antiparasites, antivirals, or antifungals during the 4 weeks prior to screening, or a viral disease that may not have received antiviral treatment during the 4 weeks prior to screening;(Screening visits can be performed after the patient recovers from infection, but the systemic antibiotic washout period needs to be greater than 2 weeks).

• Patients with asthma should be excluded if: a. forced expiratory volume in the first second (FEV1) ≤ 50% of the expected normal value, or b.Acute exacerbation of asthma within 90 days prior to screening requiring hospitalization (>24 hours), or c.Are using a daily dose of fluticasone or equivalent inhaled glucocorticoids (ICS) greater than 1000mcg;

• Subjects with asthma were initiated with inhaled corticosteroids within 4 weeks prior to the screening/induction period (for subjects who could receive a stable dose for at least 4 weeks prior to screening and whose assessed dose could be maintained throughout the study period, inhaled corticosteroids could be fluticasone propionate at a dose ≤1000μg or equivalent doses of other inhaled corticosteroids).

• Subjects have concomitant medical conditions that prevent them from completing the screening period assessment or evaluating the primary efficacy endpoint, such as:

  1. A deviated nasal septum leads to obstruction of at least one nostril
  2. Persistent drug rhinitis;
  3. The diagnosis was eosinophilic granulomatous vasculitis (Churg-Strauss syndrome), granulomatous polyvasculitis (Wegener's granuloma), Young's syndrome, Kartagener syndrome or other ciliary dyskinesia syndrome, cystic fibrosis;
  4. Suspected or confirmed fungal rhinosinusitis on imaging;

• Subjects with nasal malignancies and benign tumors (e.g., papilloma, hemangioma, etc.);

• Subjects who are unable to use MFNS or are allergic or intolerant to Mometasone furoate nasal spray;

• Subjects with a history of systemic allergy to any biological agent (except local injection site reactions);

• Pregnant or lactating women;

• Alcohol, drug and known drug dependence;

• The subjects had poor compliance in the study and could not complete the study as judged by the researcher;

• Any medical or psychiatric condition that, in the judgment of the investigator or sponsor medical reviewer, puts the subject at risk, interferes with participation in the study, or interferes with the interpretation of the study results.