A Randomized, Double-Blind, Placebo-Controlled Phase II Clinical Study to Evaluate the Efficacy and Safety of NWRD08 in Patients With HPV16/18-Positive Cervical High-Grade Squamous Intraepithelial Lesion (HSIL)
This is a randomized, double-blind, placebo controlled Phase 2 study to determine the efficacy and safety of NWRD08 administered by intramuscular (IM) injection followed by electroporation (EP) in adult women with histologically confirmed cervical high grade squamous intraepithelial lesion (HSIL) (cervical intraepithelial neoplasia grade 2 \[CIN2\] or grade 3 \[CIN3\]) associated with human papillomavirus (HPV) 16 and/or HPV18.
⁃ Subjects had to meet all of the following inclusion criteria:
⁃ 1\. Aged 18 to 60 years, female.
⁃ 2\. Confirmed by the central laboratory, histopathology results demonstrated cervical HSIL with concurrent HPV16 and/or HPV18 positivity.
⁃ 3\. Colposcopy results during screening must meet the following criteria:
• The colposcopy must be satisfactory, allowing clear visualization of the entire acetowhite area or the extent of suspected cervical intraepithelial neoplasia (CIN) lesions, including the upper border of the lesion.
• If the upper border of the lesion is unclear, endocervical curettage (ECC) results must be negative.
• The cervical lesion area must be less than 75% of the surface of the ectocervix.
⁃ 4\. Fully understand the study and voluntarily sign the informed consent form, able to communicate well with the investigator and complete all treatments, examinations, and visits as required by the study protocol. The informed consent form must be signed before performing any study-specific procedures.
⁃ 5\. At screening, the investigator judges the electrocardiogram (ECG) as normal or without clinically significant findings.
⁃ 6\. Normal function of major organs within 1 week before the first dose: Blood routine: Hemoglobin (Hb) ≥100 g/L; platelet count (PLT) ≥75×10⁹/L; white blood cell count (WBC) ≥3.0×10⁹/L; absolute neutrophil count (ANC) ≥1.5×10⁹/L.
⁃ Liver: Total bilirubin (TB) ≤1.5 × upper limit of normal (ULN); alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤1.5 × ULN; plasma albumin ≥30 g/L.
⁃ Kidney: Serum creatinine (Scr) ≤1.5 × ULN, or creatinine clearance rate ≥60 mL/min (calculated by Cockcroft-Gault formula) (if serum creatinine \>1.5 × ULN).
⁃ 7\. Women of childbearing potential must be willing to consistently and correctly use a contraceptive method with a failure rate of less than 1% per year from the time of signing the informed consent form until the end of the study. Acceptable methods include:
• Hormonal contraceptives: Combined or progestin-only methods, including oral contraceptives, injections, implants, vaginal rings, or transdermal patches. Subjects with a history of hypercoagulable states (e.g., deep vein thrombosis, pulmonary embolism) must not use hormonal contraceptives.
• Abstinence from penile-vaginal intercourse.
• Intrauterine device (IUD) or intrauterine system (IUS).
• Female subject's male partner sterilized for at least 6 months prior to study entry, and this male is the subject's sole sexual partner.
• Condom use, with emergency contraception required in case of accidents such as slippage or breakage.
• Postmenopausal patients (defined as at least 12 consecutive months of amenorrhea without alternative medical causes, with serum follicle-stimulating hormone levels within the laboratory reference range for postmenopausal women) or those sterilized for more than 12 months prior to screening may be considered not requiring contraception.