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

ConditionHigh-grade Squamous Intraepithelial Lesions (HSIL)
Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexFemale
Age25-50
SponsorShanghai BDgene Co., Ltd.

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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;

Disqualifiers

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 ;

Trial design

Design model

Sequential

Treatments tested in this trial

  • BD114VLP, or BD114

    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.

  • BD114VLP or BD114 plus Gel

    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) .

Treatment groups

12 Participants
are divided into 2 treatment groups
Group A: BD114 injectionExperimental treatment 1 intervention
Group B: BD114 gelExperimental treatment 1 intervention

Trial outcomes

Primary outcomes

1

Adverse events (AEs) and serious adverse events (SAEs)

All AEs and SAEs occurring during the study period (from informed consent signing to Week 36 post-BD114 intervention) were recorded and assessed according to the NCI-CTCAE v5.0 grading system, including their classification by System Organ Class (SOC), severity grade, number of affected Participants, and incidence rates. Gynecological AEs (beyond NCI-CTCAE v5.0 specifications) shall be evaluated by investigators for classification and severity grading according to current clinical guidelines/expert consensus.

Time frame
~36 weeks
2

Percentage of Participants with No Histologic Evidence of HSIL

Cervical tissue biopsies obtained at Week 24 and Week 36 undergo histopathological evaluation, and judge the HSIL Clearance by complete regression or disappear of the original lesions, with clearance rates calculated per the following formula: Percentage of Participants with No Histologic Evidence of HSIL (%) = Number of Participants Achieving HSIL Clearance / Total number of Participants treated with BD114 ×100%

Time frame
Week 24, Week 36

Secondary outcomes

1

Percentage of Participants with No Histologic Evidence of HSIL and No Evidence of HPV-16

Virological HPV-16 assessment was performed using clinically validated type-specific HPV testing kits, meanwhile colposcopy-guided cervical tissue biopsies are histopathologically evaluated. The calculating formula as follow: Percentage of Participants with No Histologic Evidence of HSIL and No Evidence of HPV-16 = Number of Participants with No Histologic Evidence of HSIL and No Evidence of HPV-16 / Total number of Participants treated with BD114 ×100%

Time frame
Week 24, Week 36
2

Percentage of Participants with No Evidence of HPV-16

Histological samples (cervical exfoliated cells) is detected for HPV-16 by real-time fluorescent quantifying PCR technology. The calculating formula as follow: Percentage of Participants with No Evidence of HPV-16 = Number of Participants with No Evidence of HPV-16 / Total number of Participants treated with BD114 ×100%

Time frame
Week 24, Week 36
3

Percentage of Participants with No Evidence of HSIL or LSIL

Cervical biopsies at Week 36 are performed for histopathological evaluation, no histologically evidence of HSIL or LSIL of histological samples are judged as no histology findings of HSIL or LSIL. The calculating formula as follow: Percentage of Participants with No Evidence of HSIL or LSIL = Number of Participants with No Evidence of HSIL or LSIL / Total number of Participants treated with BD114 ×100%

Time frame
Week 36
4

Percentage of Participants with No Evidence of HSIL or LSIL and No Evidence of HPV-16

Cervical biopsies at Week 36 are performed for histopathological evaluation, no histologically evidence of HSIL or LSIL of histological samples are judged as no histology findings of HSIL or LSIL. Histological samples (cervical exfoliated cells) is detected HPV-16 by real-time fluorescent quantifying PCR technology. Calculation Formula: Percentage of Participants with No Evidence of HSIL or LSIL and No Evidence of HPV-16 = Number of Participants A with No Evidence of HSIL or LSIL and No Evidence of HPV-16 / Total number of Participants treated with BD114 ×100%

Time frame
Week 36

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Shanghai BDgene Co., Ltd.

Lead sponsor

Obstetrics & Gynecology Hospital of Fudan University

Collaborator

Source ClinicalTrials.gov
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