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

Официальное название

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)

Обзор

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.

Подробное описание

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.

Вмешательства

• Генная терапия 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.
• Генная терапия 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 tim

Первичные конечные точки

• Adverse events (AEs) and serious adverse events (SAEs) [Срок оценки: ~36 weeks]
• Percentage of Participants with No Histologic Evidence of HSIL [Срок оценки: Week 24, Week 36]

Вторичные конечные точки (8)

• Percentage of Participants with No Histologic Evidence of HSIL and No Evidence of HPV-16 [Срок оценки: Week 24, Week 36]
• Percentage of Participants with No Evidence of HPV-16 [Срок оценки: Week 24, Week 36]
• Percentage of Participants with No Evidence of HSIL or LSIL [Срок оценки: Week 36]
• Percentage of Participants with No Evidence of HSIL or LSIL and No Evidence of HPV-16 [Срок оценки: Week 36]
• Changes in Serum Inflammatory Cytokine (IL-1/IL-6/TNF-α/IFN-γ) Levels Relative to Baseline [Срок оценки: Arm 1: at Day 2, Week 1, Week 2, Week 4, Week 12, Week 24, and Week 36. Arm 2: at Day 10, Day 15, Day 22, Day 36, Week 12, Week 24, and Week 36]
• Concentrations of Cas9 Protein and gRNA in Peripheral Blood [Срок оценки: Arm 1: at Day 2, Week 1, Week 4, Week 12. Arm 2: at Day 10, Day 15, Day 36, Week 12]
• Detection of Anti-p24/Cas9 Protein Antibodies in Peripheral Blood [Срок оценки: Arm 1: Week 2, Week 4, Week 36. Arm 2: Day 22, Day 36, Week 36]
• Off-Target Analysis [Срок оценки: Arm 1: Week 1. Arm 2: Day 15]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Obstetrics & Gynecology Hospital of Fudan University — Шанхай

Идентификаторы

NCT: NCT07170254 · BD-HSIL-114001

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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