High-grade Squamous Intraepithelial Lesions of the Cervix Associated With Human Papillomavirus (HPV) Type 16 and/or HPV Type 18 Infection
Conditions
Keywords
gene therapy, Adeno Virus
Brief summary
The goal of this study is to learn about the safety, tolerability, immunogenicity and preliminary efficacy of BBM-C101 injection in patients with High-Grade Squamous Intraepithelial Lesion of the cervix. This study include two phases: Phase I and Phase IIa .
Interventions
DRUGBBM-C101
hypodermic injection , once a week, for a total of 4 administrations. Low dose group， Middle dose group； High dose group
Sponsors
Shanghai Mianyi Biopharmaceutical Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
1. Histologically confirmed HPV16 and/or HPV18 associated HSIL. 2. Colposcopy findings at screening at each study center must meet all of the following conditions: The colposcopy examination should be satisfactory and The ECC result must be negative. 3. Women of childbearing potential must agree to use highly effective contraception together with their partner throughout the study and for at least 1 year after the first dose ; f and a serum pregnancy test within 7 days prior to enrollment must be negative . 4. Willing to voluntarily participate in the study and provide written informed consent . 5. In the opinion of the Investigator, the participant is expected to demonstrate good compliance and be able to complete all scheduled visits and follow-up assessments in accordance with the study protocol . \-
Exclusion criteria
1. During screening, cytological or histopathological shows any of the following results: adenocarcinoma in situ (AIS), atypical glandular cells-favor neoplasia (AGC-FN), or invasive carcinoma . 2. Participants who have received any treatment for HPV positivity or cervical HSIL prior to study drug. 3. History of previous therapeutic HPV vaccination ( except for the licensed prophylactic HPV vaccines ). 4. Participants who have used any local or systemic immunosuppressive agents prior to the first administration of BBM-C101 injection . 5. Received any licensed vaccines within 2 weeks prior to study drug administration . 6. Participants with acute cervical inflammation or acute exacerbation of chronic cervical disease . 7. Positive results were obtained in the tests for hepatitis C virus antibody, human immunodeficiency virus (HIV). 8. Having participated in other clinical trials before signing the informed consent form, including studies involving investigational drugs or devices. 9. Participants who are unable or unwilling to undergo colposcopy, or have contraindications to colposcopy. 10. Participants who have received any gene therapy treatment prior to screening, or plans to receive any other gene therapy treatment during the study period. 11. Participants with clinically significant abnormal values in laboratory tests during screening, as determined by the Investigator to increase risk to the participant's participation in the clinical trial . This includes, but is not limited to, any of the following: 1. White blood cell count \< 3.0 × 10⁹/L; 2. Hemoglobin \< 90 g/L; 3. Platelet \< 100 × 10⁹/L; 4. Aspartate aminotransferase or alanine aminotransferase \> 2 × upper limit of normal (ULN); 5. Total bilirubin \> 1.5 × ULN; 6. Creatinine \> 1.5 × ULN. 12. Participants with a history or diagnosis of autoimmune diseases, including but not limited to Crohn's disease, ulcerative colitis, systemic lupus erythematosus, sarcoidosis, Wegener's granulomatosis, Graves' disease, rheumatoid arthritis, hypophysitis , uveitis, autoimmune hepatitis, systemic sclerosis, autoimmune vasculitis, autoimmune neuropathy (Guillain-Barré syndrome), etc. 13. Participants with active infections requiring systemic anti-infective therapy. 14. Participants with unstable cardiovascular or cerebrovascular diseases, defined as clinical cardiovascular event (such as unstable angina, myocardial infarction, stroke, etc.) occurring within 3 months prior to screening; participants with severe uncontrolled hypertension (systolic blood pressure ≥ 160 mmHg or diastolic blood pressure ≥ 100 mmHg). 15. Participants with a known history of malignant tumors in any organ/system (regardless of evidence of local recurrence or metastasis) . 16. Participants with a history of severe allergic diseases ( e.g., allergy-related shock, dyspnea, angioedema) ). 17. Active drug or alcohol use or dependence that, in the opinion of the Investigator, would interfere with adherence to study requirements . 18. Major surgery or significant trauma within 4 weeks prior to the first dose . 19. Pregnant or breastfeeding (lactating). 20. Any other conditions judged by the Investigator that may affect a participant's safety or compliance . \-
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Phase I: Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs); Incidence of dose limiting toxicity (DLT) events | within 5 weeks |
| Phase I: Determine the Maximum Tolerated Dose (MTD) and/or the Recommended Phase II Dose (RP2D) | within 5 weeks |
| Phase IIa： The percentage of cervical lesions that have regressed to CIN1 or normal as confirmed by virology and histopathology | within 52 weeks |
Secondary
| Measure | Time frame |
|---|---|
| Phase I: The percentage of cervical lesions that have regressed to CIN1 or normal, as confirmed by virology and histopathology studies | within 52 weeks |
| Phase I&Phase IIa: Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs) | within 52 weeks |
| Phase I&Phase IIa: Percentage of HPV and E6E7 mRNA elimination | within 52 weeks |
Countries
China
Contacts
CONTACTXia Wu, PhD
Outcome results
None listed