A Phase II Clinical Trial Evaluating the Efficacy and Safety of SYS6026 Injection in Participants With HPV16 or 18-related High-grade Cervical Squamous Intraepithelial Lesions

A Phase II Clinical Trial Evaluating the Efficacy and Safety of SYS6026 Injection in Participants With HPV16 or 18-related High-grade Cervical Squamous Intraepithelial Lesions

This trial is a multicenter, randomized, double-blind, placebo-controlled Phase II clinical study designed to evaluate the efficacy and safety of SYS6026 at different doses compared to placebo in treating patients with HPV16 or 18-related high-grade cervical squamous intraepithelial lesions (HSIL).

Approximately 175 participants were planned to be enrolled, initially randomized at a 2:2:2:1 ratio to SYS6026 three dose groups and placebo groups.

Inclusion Criteria:

• Age must be 18 years old or above;

• During the screening period, the research center confirmed participants with HPV type 16 and/or type 18 cervical infection;

• During screening, the research center confirmed histological evidence of cervical HSIL (CIN grade 2~CIN3) (lesions may be obtained within 3 months prior to the first study treatment);

• Colposcopy results at each research center during the screening period must meet the following conditions: 1) Fully visible squamous-columnar epithelial junction (type I or type II transformation zone), with fully visible upper white acetic acid epithelial or suspected CIN lesions; 2) Cervical lesions can be touched and sampled by biopsy instruments, and the cervical lesions are sufficiently large to ensure visible lesions remain for observation during the study period;

• Consent was given to undergo lesion biopsy during the screening period and to perform surgical resection or biopsy at 36 weeks after the first vaccination;

• During the screening period, sufficient lesion tissue biopsy samples and cervical swab samples can be obtained for CIN and HPV testing in the central laboratory;

• Major organ function was normal within one week prior to the first vaccination:

  1. Blood count: Hb≥100 g/L; PLT≥100×109/L； Neutrophil count≥ 1.5×109/L;
  2. Liver: TB≤ 1.5× ULN; ALT and AST ≤ 2.5× ULN; Plasma albumin ≥30 g/L;
  3. Kidney: Scr ≤ 1.5× ULN, or creatinine clearance ≥60 mL/min (calculated by Cockcroft-Gault formula);
  4. Coagulation function: PT, APTT, and INR ≤1.5× ULN;

• The investigator determined that the ECG during the screening period was normal or without clinically significant results; 9) Normal vital sign test results:

  1. On the day of the first vaccination, the axillary temperature ≤ 37.0°C;
  2. Systolic pressure < 140 mmHg and diastolic pressure < 90 mmHg;

• Eligible participants with fertility must agree to use reliable contraceptive methods (hormonal contraceptives, barrier therapy, or abstinence) with their partner during the trial and for at least one year after the last dose; Female participants of childbearing age must have a negative blood pregnancy test within 7 days prior to enrollment;

• Fully understand this clinical trial and voluntarily sign a written informed consent form

Exclusion Criteria:

• Screening combined with other high-risk HPV subtypes (HPV 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68);
• Cases with VIN/VAIN/AIN or AIS or other lesions should be excluded.
• During screening, cytological or histopathological examination yields any of the following: AIS, AGC-FN, invasive cancer, etc.;
• HSIL treatment within 4 weeks prior to the first vaccination;
• Previous receipt of therapeutic HPV vaccines (approved preventive HPV vaccines are permitted);
• Received any live vaccine injection within 4 weeks prior to the first vaccination or received any live vaccine injection within 2 weeks;
• Previous or current history of other malignant tumors (except for the following tumors: ductal carcinoma in situ that has been fully treated and completely cured, basal cell carcinoma of the skin, superficial bladder tumors, or any malignant tumor cured more than 2 years prior to study entry);
• Having active autoimmune disease or a history of autoimmune disease;
• Other immune dysfunction conditions, such as receiving immunosuppressive or immunosuppressive therapy within 3 months (continuous oral or infusion for more than 14 days); or those who have received whole blood, plasma, or immunoglobulin therapy within the past month; Or those with known immunological impairment or impairment diagnosed by hospitals, or any condition leading to functional splenectomy or splenectomy;
• A history of severe allergy to any vaccine or known components of SYS6026 injections;
• Participated in other clinical trials within 4 weeks prior to the first use of the investigational vaccine;
• Surgical procedure or significant trauma within 4 weeks prior to the first use of the investigational vaccine;
• Fever (axillary temperature ≥ 38.0°C) within 3 days before first use of the trial vaccine, acute illness or acute exacerbation of chronic disease within the first 5 days, or fever-reducer, analgesic, or anti-allergy medication taken within 3 days before the first trial vaccine dose; Hepatitis C virus infection;
• Active hepatitis B (hepatitis B virus titer> 1000 copies/mL or 200 IU/mL), allowing prophylactic antiviral therapy other than interferon;
• History of immunodeficiency, or positive HIV antibody test;
• Accompanied by systemic active bacterial, fungal, or viral infections (defined as requiring intravenous antibacterial, antifungal, or antiviral drug treatment);
• Long-term (≥7-day) systemic use of glucocorticoids (prednisone ≥20 mg/day or equivalent dose) or other immunosuppressive treatments (short-term glucocorticoids are allowed for preventive treatment; Topical use of glucocorticoids is permitted, such as ocular, intra-articulary, intranasal, and inhaled types. Current or planned use of antirheumatic or immunomodulatory drugs, such as azathioprine, cyclophosphamide, cyclosporine, methotrexate, and TNFα inhibitors (such as infliximab, adalimumab, or etanercept), etc.;
• History of solid organ transplantation or bone marrow transplantation;
• Pregnant or breastfeeding women;
• Other circumstances that may interfere with participant participation in study procedures or may not align with the maximum benefit or impact on study outcomes: such as a history of mental illness, drug use, or drug abuse, any other clinically significant diseases or conditions, such as medically unstable diseases (e.g., chronic kidney failure; Angina, myocardial ischemia or infarction, grade 3 or higher congestive heart failure, cardiomyopathy, or clinically significant arrhythmias), etc.