A Clinical Study on the Evaluation of BD114 for the Treatment HPV-16-Related Cervical HSIL

This study is an open-label, two-arm, balanced-group, single-dose, non-randomized exploration clinical study. A total of 12 patients with HPV-16 Related HSIL of the Cervix will be enrolled and divided into two arms. Participants in Arm 1 receive topically BD114 intraepithelial injection of lesions, and Participants in Arm 2 receive BD114 gel topical application of lesions, with 6 Participants allocated in each arm. Each study arm is further divided into the low-dose subgroup assigned 1 Participant and the high-dose subgroup assigned 5 Participants. The total study duration for each Participant is 40 weeks (including screening stage). The treatment-emergent adverse events (TEAEs) for safe evaluation, components detection of the BD114 for pharmacokinetics (PK) assessment, histologically lesion regression and virologically HPV-16 clearness for efficacy evaluation are observed and explored during follow-up visits.

Inclusion criteria

• Female, aged 25 to 50 years, without childbearing demand;
• Confirmed histopathological evidence of cervical HSIL (CIN3) at the screening period or within 1 month prior to screening;
• Confirmed cervical HPV-16 positive by HPV test during the screening period or within 1 month prior to screening, without other high-risk HPV types detected;
• Complete visibility of both the squamocolumnar junction (SCJ Types 1/2) and the upper margin of acetate-white epithelium or suspected HSIL lesions under colposcopy examine during the screening period or within 1 month prior to screening;
• No evidence of precancerous lesions or malignancy by endocervical curettage (ECC) ;
• The biopsy sampling of cervical lesions are performed;
• Visible residual cervical lesions after screening biopsy;
• Willing to maintain abstinence or use a highly effective contraceptive method (oral contraceptives, injections, implants, or barrier methods) for women of childbearing potential (WOCBP) from enrollment until Week 36, or her partner undergone surgical sterilization (e.g., vasectomy);
• Good compliance to protocol-specified procedure in study duration assessed by investigator;
• Voluntarily participating in the study and willing to provided signed informed consent.

Exclusion criteria

• Positive detection of antibodies or viral test of human immunodeficiency virus (HIV), or hepatitis B virus (HBV), or hepatitis C virus (HCV), or Treponema pallidum (TP) at screening;
• Confirmed histopathologically epithelial carcinoma, glandular carcinoma or precancerous lesions in the endometrium at screening;
• Confirmed histopathologically or macroscopically high-grade intraepithelial neoplasia or invasive carcinoma in the vulva, vagina or anus at screening;
• HSIL with partial location in cervical canal and incomplete colposcopic visualization ;
• Undergone the treatment for cervical HSIL within 4 weeks prior to screening;
• Vaccination history of any therapeutic HPV vaccine;
• Family history of malignancy, or a history/current presence of any malignant tumor;
• Severe uncontrolled diseases of major organs, including but not limited to: acute myocardial infarction, stroke, liver cirrhosis, severe kidney disease, diabetes mellitus, chronic obstructive pulmonary disease (COPD), hematologic disorders, psychiatric disorders, etc;
• Pregnant (a positive urine or serum pregnancy test) or lactating women;
• Participating in another drug or device clinical trial at screening, or participated in one within 3 months prior to screening;
• The history of any form of gene and/or cell therapy;
• Drug abuse or alcohol addiction no compliance to protocol-specific procedure;
• Any other condition unsuitable for participating this study judged by the investigator.