Evaluation of the Safety, Tolerability, Immunogenicity and Preliminary Efficacy of BBM-C101 Injection in Patients With Cervical High-Grade Squamous Intraepithelial Lesion(HSIL)

A Phase I/ IIa, Open-Label, Single-Arm, Dose-Escalation and Dose Expansion Study to Evaluate the Safety, Tolerability, Immunogenicity and Preliminary Efficacy of BBM-C101 Injection in Patients With Cervical High-Grade Squamous Intraepithelial Lesions.

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 .

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 .

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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 .

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