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

An Open-Label, Two-Arm, Non-Randomized Clinical Study On The Safety And Efficacy Of Instantaneous CRISPR/Cas9 Gene Editing Therapy For Treating Chinese Patients With HPV-16-Related High-Grade Squamous Intraepithelial Lesions (HSIL)

This study is intented to evaluate the safety, and tolerability and preliminary efficacy of Instantaneous CRISPR/Cas9 Gene Editing Therapy (BD114 virus-like particle, also BD114) for the treatment of high-grade squamous intraepithelial lesions (HSIL) associated with HPV-16 infection.

This study is an open-label, two-arm, balanced-group, single-dose, non-randomized exploration clinical study. A total of 6 patients with HPV-16 Related HSIL of the Cervix will be enrolled and divided into two arms. Participant in Arm 1(n=1) receive topically low-dose of BD114 with intraepithelial injection of lesions, and participants in Arm 2 (n=5) receive high-dose of BD114 with intraepithelial injection of lesions. The total follow-up 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 or clearness and virologically HPV-16 clearness for efficacy evaluation are conducted and explored during follow-up visits.

Inclusion Criteria:

1. Female, aged 18 to 50 years, without childbearing demand;
2. Confirmed histopathological evidence of cervical HSIL (CIN3) at the screening period or within 1 month prior to screening;
3. 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;
4. 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;
5. No evidence of precancerous lesions or malignancy by endocervical curettage (ECC) ;
6. The biopsy sampling of cervical lesions are performed;
7. Visible residual cervical lesions after screening biopsy;
8. 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);
9. Good compliance to protocol-specified procedure in study duration assessed by investigator;
10. Voluntarily participating in the study and willing to provided signed informed consent.

Exclusion Criteria:

1. 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;
2. Confirmed histopathologically epithelial carcinoma, glandular carcinoma or precancerous lesions in the endometrium at screening;
3. Confirmed histopathologically or macroscopically high-grade intraepithelial neoplasia or invasive carcinoma in the vulva, vagina or anus at screening;
4. HSIL with partial location in cervical canal and incomplete colposcopic visualization ;
5. Undergone the treatment for cervical HSIL within 4 weeks prior to screening;
6. Vaccination history of any therapeutic HPV vaccine;
7. Family history of malignancy, or a history/current presence of any malignant tumor;
8. 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;
9. Pregnant (a positive urine or serum pregnancy test) or lactating women;
10. Participating in another drug or device clinical trial at screening, or participated in one within 3 months prior to screening;
11. The history of any form of gene and/or cell therapy;
12. Drug abuse or alcohol addiction no compliance to protocol-specific procedure;
13. Any other condition unsuitable for participating this study judged by the investigator.