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

Official title

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.

Overview

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

• Drug BBM-C101
  hypodermic injection , once a week, for a total of 4 administrations. Low dose group， Middle dose group； High dose group

Primary outcome measures

• Phase I: Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs); Incidence of dose limiting toxicity (DLT) events [Time frame: within 5 weeks]
• Phase I: Determine the Maximum Tolerated Dose (MTD) and/or the Recommended Phase II Dose (RP2D) [Time frame: within 5 weeks]
• Phase IIa： The percentage of cervical lesions that have regressed to CIN1 or normal as confirmed by virology and histopathology [Time frame: within 52 weeks]

Secondary outcome measures (3)

• Phase I: The percentage of cervical lesions that have regressed to CIN1 or normal, as confirmed by virology and histopathology studies [Time frame: within 52 weeks]
• Phase I&Phase IIa: Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs) [Time frame: within 52 weeks]
• Phase I&Phase IIa: Percentage of HPV and E6E7 mRNA elimination [Time frame: within 52 weeks]

Eligibility criteria

Inclusion criteria

• Histologically confirmed HPV16 and/or HPV18 associated HSIL.
• 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.
• 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 .
• Willing to voluntarily participate in the study and provide written informed consent .
• 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

• 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 .
• Participants who have received any treatment for HPV positivity or cervical HSIL prior to study drug.
• History of previous therapeutic HPV vaccination ( except for the licensed prophylactic HPV vaccines ).
• Participants who have used any local or systemic immunosuppressive agents prior to the first administration of BBM-C101 injection .
• Received any licensed vaccines within 2 weeks prior to study drug administration .
• Participants with acute cervical inflammation or acute exacerbation of chronic cervical disease .
• Positive results were obtained in the tests for hepatitis C virus antibody, human immunodeficiency virus (HIV).
• Having participated in other clinical trials before signing the informed consent form, including studies involving investigational drugs or devices.
• Participants who are unable or unwilling to undergo colposcopy, or have contraindications to colposcopy.
• Participants who have received any gene therapy treatment prior to screening, or plans to receive any other gene therapy treatment during the study period.
• 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:

• White blood cell count < 3.0 × 10⁹/L;
• Hemoglobin < 90 g/L;
• Platelet < 100 × 10⁹/L;
• Aspartate aminotransferase or alanine aminotransferase > 2 × upper limit of normal (ULN);
• Total bilirubin > 1.5 × ULN;
• Creatinine > 1.5 × ULN.
• 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.
• Participants with active infections requiring systemic anti-infective therapy.
• 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).
• Participants with a known history of malignant tumors in any organ/system (regardless of evidence of local recurrence or metastasis) .
• Participants with a history of severe allergic diseases ( e.g., allergy-related shock, dyspnea, angioedema) ).
• Active drug or alcohol use or dependence that, in the opinion of the Investigator, would interfere with adherence to study requirements .
• Major surgery or significant trauma within 4 weeks prior to the first dose .
• Pregnant or breastfeeding (lactating).
• Any other conditions judged by the Investigator that may affect a participant's safety or compliance .

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Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 4 centers

• Peking University People's Hospital — Beijing
• The Second Affiliated Hospital of Chongqing Medical University — Chongqing
• Henan Provincial People's Hospital — Zhangzhou
• Qilu Hospital of Shandong University — Jinan

Identifiers

NCT: NCT07668960 · BBM040-CLN1001

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗