Evaluation of NWRD09 for Female Participants With Persistent HPV16 Infection

Официальное название

A Phase I/IIa, Randomized, Double Blind, Placebo Controlled, Dose Escalation and Cohort Expansion Study to Evaluate the Safety, Tolerability, Immunogenicity, and Efficacy of NWRD09 Injection in Female Participants With Persistent HPV16 Infection

Обзор

This is a two-part, phase I/IIa study, intended to evaluate the safety, tolerability, immunogenicity, and efficacy of NWRD09 in female participants with persistent HPV16 infection, and to determine the MTD, and/or RP2D of NWRD09.

Вмешательства

• Биопрепарат NWRD09
  Participants will receive 4 injections of NWRD09 via IM to the lateral deltoid region of the upper arm, at D1 (W0D1), D15 (W2D1), D29 (W4D1) and D85 (W12D1)
• Биопрепарат Placebo
  Participants will receive 4 injections of Placebo via IM to the lateral deltoid region of the upper arm, at D1 (W0D1), D15 (W2D1), D29 (W4D1) and D85 (W12D1)

Первичные конечные точки

• Incidence and severity of local and systemic adverse events (AEs). [Срок оценки: Up to Week 28]

Вторичные конечные точки (5)

• Proportion of participants with clearance of HPV16 [Срок оценки: Weeks 16 and 28]
• Proportion of participants with cervical cytology normal/ASC-US/LSIL [Срок оценки: Week 16 and 28]
• For participants with histopathological LSIL at baseline, proportion of participants with histopathological regression to NSIL [Срок оценки: Week 28]
• T cell responses to the separate or combined protein peptide pools of HPV16 E1, E2, E6 and E7 proteins [Срок оценки: Weeks 6, 16 and 28]
• Serum HPV16 E6/E7-specific IgG antibodies will be determined by ELISA [Срок оценки: Weeks 6, 16 and 28]

Критерии участия

Критерии включения

• Participants who have fully understood the study, able and willing to comply with all study procedures, and voluntarily sign written ICF;
• Female participants aged 18-60 years (inclusive) at the time of signing the ICF;
• Persistent HPV16 infection, defined as virologically confirmed HPV16 positivity persisting for ≥ 6 months before screening (e.g., participants must provide investigator-approved evidence of HPV16 infection ≥ 6 months prior to screening and be HPV16 positive at the time of screening);
• Participants must have a confirmed cytological results of atypical squamous cells cannot exclude high-grade squamous intraepithelial lesion (ASC-H) or high-grade squamous intraepithelial lesion (HSIL) at the time of screening (histopathological confirmed cervical/vaginal/vulvar LSIL are acceptable but not required);
• Satisfactory colposcopy at screening;
• Normal major organ functions at screening;
• Women of child-bearing potential must have a negative serum pregnancy test result at screening. All WOCBP participants agree to voluntarily use effective contraception, from signing the ICF to the end of the study. In addition, female participants must agree not to donate eggs during this period.

Критерии исключения

• Histopathological confirmed high-grade cervical, vulvar, vaginal or anal intraepithelial lesions (including endocervical adenocarcinoma-in-situ \[AIS\]) or invasive cancer, OR cervical cytology results showing squamous cell carcinoma (SCC), atypical glandular cells (AGC), or AIS at screening;
• Negative for HPV16 as confirmed by real-time quantitative polymerase chain reaction (RT-qPCR) at screening;
• Comorbid infectious diseases, such as acute pelvic inflammatory disease, urinary tract infection, or other active infections requiring systemic treatment prior to the first injection;
• Participants with unresolved vaginal/cervical conditions prior to the first injection that could affect clinical response (e.g., common sexually transmitted infections such as gonorrhoea, genital herpes, etc.);
• Positive serological test results at screening for human immunodeficiency virus (HIV), treponema pallidum antibody, or hepatitis B virus surface antigen (HBsAg) positive; or hepatitis C virus antibody (HCV-Ab) positive and hepatitis C virus (HCV) ribonucleic acid (RNA) quantitative > the lower limit of the positive detection value of the study site;
• Significant abnormalities at the screening ECG, including QTc interval > 470 msec (average of triplicate measurements corrected for heart rate using Fridericia's formula), or history/presence of clinical symptoms of cardiac diseases that is not well controlled, such as New York Heart Association (NYHA) Class 2 or higher heart failure, unstable angina, myocardial infarction within the past 6 months, and clinically significant supraventricular or ventricular arrhythmia requiring treatment or intervention;
• Systemic corticosteroid use (e.g., > 10 mg/day prednisone for > 1 week) within 30 days before screening, excluding hormone replacement therapy and local/topical use (e.g., ocular, intratracheal);
• Immunosuppressant use (> 1 week) within 30 days or 5 drug half-lives (whichever is longer) before screening (including but not limited to cyclosporine, tacrolimus, azathioprine, 6-mercaptopurine, or antilymphocyte globulin);
• Current or planned use of disease-modifying antirheumatic drugs (DMARDs, e.g., azathioprine, cyclophosphamide, cyclosporine, methotrexate) or biologic DMARDs (e.g., infliximab, adalimumab, etanercept) during the study;
• Received any vaccine (other than HPV prophylactic vaccines) within 8 weeks before screening or plan to receive any vaccine during the study;
• History of therapeutic HPV vaccination.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

США · 1 центр

• Columbia University Medical Center — New York

Идентификаторы

NCT: NCT07536282 · NWRD09-103

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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