BCG for Therapeutic Use Phase I Clinical Trial

Prior treatment

• Patients with acute or chronic active hepatitis B \[Hepatitis B Surface Antigen (HBsAg) positive and peripheral blood hepatitis B virus deoxyribonucleic acid (DNA) copy number ≥103/mL\], hepatitis C virus (HCV) antibody positive (HCV copy number ≥103/mL), human immunodeficiency virus (HIV) antibody positive, syphilis specific antibody positive, C-TST test strongly positive, active tuberculosis, patients who are receiving anti-tuberculosis treatment, and other patients with fever or acute infectious diseases.
• New York Heart Association (NYHA) heart function grade ≥3. 2. Patients with tumors of other genitourinary system or other organs. 3. Patients with carcinoma in situ (Tis stage) or muscular invasive bladder urothelial carcinoma (T2 stage and above).
  • 4\. Received any BCG treatment for NMIBC within 2 years before enrollment. Or recurrence of NMIBC after BCG treatment at any time.
  • 5\. Patients who had received chemotherapy, radiotherapy or immunotherapy within 4 weeks before admission (except for immediate postoperative intravesical chemotherapy).
  • 6\. Pregnant or lactating women (currently breastfeeding or less than one year after delivery although there is no artificial breastfeeding), women of childbearing age who cannot guarantee effective contraception during the trial period, and plan to have a pregnancy plan within 6 months after the last dosing (Including the partner of the male subject).
  • 7\. It is known or suspected that bladder perforation or abnormal conditions such as prolonged operation time and massive bleeding occur during the operation.
  • 8\. The investigator judged that there was severe gross hematuria before enrollment, and suspected that the surgical wound had not healed or the urinary tract mucosa was damaged.
  • 9\. with cystitis or having received other intravesical drug therapy and severe bladder irritation,which was judged by the investigator to be expected to affect the evaluation of this study.
  • 10\. Complete bladder incontinence, defined as the use of more than 6 pads within 24 hours.
  • 11\. Participated in clinical trials of other drugs within 3 months before enrollment.
  • 12\. Regular drinkers within six months before enrollment, such as those who drink more than 14 units of alcohol per week (1 unit =360 mL beer with 5% alcohol, or 45 mL spirits with 40% alcohol, or 150 mL wine with 12% alcohol); Or have a history of drug abuse or drug use.
  • 13\. The investigator believes that there may be any conditions that increase the risk of the subjects or interfere with the execution of the clinical trial.

Other illness

• Those who have immunodeficiency or impairment (such as AIDS patients), who are using immunosuppressive drugs or radiotherapy that are likely to cause systemic BCG disease reaction.
• Allergic to BCG vaccine and its excipients.
• Patients with a history of severe adverse reactions to BCG vaccine such as BCG septicemia or systemic infection.
• Patients with a history of serious diseases of cardiovascular, cerebrovascular, lung, liver, kidney and other important organs, or those with severe hypertension or diabetes that can not be controlled clinically judged by the investigators; Patients with symptomatic urinary tract infections.

Other

• 1\. Any of the following:

• 1\. Patients aged 18 years and over after transurethral resection of non-muscular invasive bladder cancer, both male and female.
• 2\. Voluntarily participate in the trial, provide valid identification, fully informed and signed a written informed consent form.
• 3\. Eastern Cooperative Oncology Group (ECOG) score: 0 \~ 2. 4. According to the Guidelines for the Diagnosis and Treatment of Bladder Cancer (2022 edition), patients with histologically confirmed non-muscular invasive bladder cancer (NMIBC) who are assessed to be medium or high risk and need BCG intravesical instillation therapy (Patients who need secondary electroresection can be included in the study after the second electroresection is completed and the pathological results are confirmed to be medium-or high-risk non-muscular invasive bladder cancer). Excluding carcinoma in situ.
• 5\. Clinical laboratory tests meet the following characteristics:
• Blood routine: no hematopoietic growth factor or transfusion support was used within 14 days before enrollment, including absolute neutrophil count (ANC) ≥1500/mm3 or ≥1.5×109/L; Platelet ≥100000/mm3 or 100×109/L; Hemoglobin ≥9 g/dL.
• Liver function: total serum bilirubin ≤1.5× upper limit of normal (ULN), total serum bilirubin \<3×ULN, aspartate and alanine aminotransferase (AST and ALT) ≤2.5×ULN in subjects with Gilbert syndrome.
• Renal function: creatinine clearance ≥45 mL/min (estimated according to Cockcroft Gault formula) or serum creatinine ≤1.5×ULN.
• Coagulation function: activated partial thromboplastin time (APTT) ≤1.5×ULN, International normalized ratio (INR) ≤1.5×ULN.