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

NCT ID: NCT07170254

Last Updated: 2025-09-12

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-09-30
• Study Completion Date: 2026-12-31

Brief Summary

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.

Detailed Description

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.

Conditions

High-grade Squamous Intraepithelial Lesions (HSIL)

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

BD114 injection

Subgroup 1: Low-dose (n=1)

• Small lesions (≤5 mm^2): BD114 injection, 0.2 mL
• Large lesions (>5 mm^2): BD114 injection 0.4 mL

Subgroup 2: High-dose (n=5)

• Small lesions (≤5 mm^2): BD114 injection, 0.3 mL
• Large lesions (>5 mm^2): BD114 injection 0.6 mL

Group Type: EXPERIMENTAL

BD114VLP, or BD114

Intervention Type: GENETIC

CRISPR/Cas9 instantaneous gene editing therapy, called BD114VLP (also BD114) which is a developing product of gene therapy from modified third-generation integrated defective lentivirus, can deliver gRNA/Cas9 ribonucleoprotein complex (RNP). It works to knock out or knock down HPV-16 E6/E7 genes integrated in HSIL cell genome resulting to lesion clearness or regression.

A single dosing BD114 injection by topical intraepithelial injection of HSIL lesion.

BD114 gel

Subgroup 1: Low-dose (n=1)

• Small lesions (≤5 mm^2): BD114 gel, 0.1 mL
• Large lesions (>5 mm^2): BD114 gel, 0.2 mL

Subgroup 2: High-dose (n=5)

• Small lesions (≤5 mm^2): BD114 gel, 0.2 mL
• Large lesions (>5 mm^2): BD114 gel, 0.4 mL

Group Type: EXPERIMENTAL

BD114VLP or BD114 plus Gel

Intervention Type: GENETIC

Genetic: BD114VLP or BD114 plus Gel CRISPR/Cas9 instantaneous gene editing therapy, called BD114VLP (also BD114) which is a developing product of gene therapy from modified third-generation integrated defective lentivirus, can deliver gRNA/Cas9 ribonucleoprotein complex (RNP). It works to knock out or knock down HPV-16 E6/E7 genes integrated in HSIL cell genome resulting to lesion clearness or regression.

Multiple dosing BD114 gel (BD114 injection :Gel, 1:1) topical application on HSIL, one time every other day, total 5 times (D0, D2, D4, D6, and D8) .

Interventions

BD114VLP, or BD114

CRISPR/Cas9 instantaneous gene editing therapy, called BD114VLP (also BD114) which is a developing product of gene therapy from modified third-generation integrated defective lentivirus, can deliver gRNA/Cas9 ribonucleoprotein complex (RNP). It works to knock out or knock down HPV-16 E6/E7 genes integrated in HSIL cell genome resulting to lesion clearness or regression.

A single dosing BD114 injection by topical intraepithelial injection of HSIL lesion.

Intervention Type: GENETIC

BD114VLP or BD114 plus Gel

Genetic: BD114VLP or BD114 plus Gel CRISPR/Cas9 instantaneous gene editing therapy, called BD114VLP (also BD114) which is a developing product of gene therapy from modified third-generation integrated defective lentivirus, can deliver gRNA/Cas9 ribonucleoprotein complex (RNP). It works to knock out or knock down HPV-16 E6/E7 genes integrated in HSIL cell genome resulting to lesion clearness or regression.

Multiple dosing BD114 gel (BD114 injection :Gel, 1:1) topical application on HSIL, one time every other day, total 5 times (D0, D2, D4, D6, and D8) .

Intervention Type: GENETIC

Eligibility Criteria

Inclusion Criteria

1. Female, aged 25 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.

• Minimum Eligible Age: 25 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Obstetrics & Gynecology Hospital of Fudan University

OTHER

Sponsor Role: collaborator

Shanghai BDgene Co., Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Obstetrics & Gynecology Hospital of Fudan University

Shanghai, , China

Site Status: RECRUITING

Countries

China

Central Contacts

Fujun Li, M.D.

Role: CONTACT

fujun.li@bdgene.cn

086-191 2131 1061

Long Sui, M.D.

Role: CONTACT

suilong@sh163.net

086-138 0178 8118

Facility Contacts

Long Sui, M.D.

Role: primary

suilong@sh163.net

086-138 0178 8118

Role: backup

suilong@sh163.net

Other Identifiers

BD-HSIL-114001

Identifier Type: -

Identifier Source: org_study_id