A Randomized Double-Blind, Placebo-controlled Phase II Trial With Safety Run-In of Intramuscular pNGVL4a-Sig/E7(Detox)/HSP70 and TA-CIN for the Treatment of Patients With HPV16+ Atypical Squamous Cells of Undetermined Significance (ASC-US) or Cannot Exclude High Grade SIL (ASC-H) Cytology or Low-grade Squamous Intraepithelial Lesion (LSIL)
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 16
- 试验地点
- 12
- 主要终点
- Incidence of Treatment-Emergent Adverse Events as assessed by CTCAE v5.0
研究概览
简要总结
- To evaluate the safety and tolerability of the dual IM pNGVL4a Sig/E7(detox)/HSP70 DNA and single IM TA-CIN immunization regimen
- To evaluate the efficacy of dual IM pNGVL4a-Sig/E7(detox)/HSP70 DNA and single IM TA-CIN immunization regimen on Human Papillomavirus (HPV) 16 clearance by Month 6
详细描述
Patients with human papillomavirus type 16 (HPV16) infection and low-grade cervical dysplasia [low-grade squamous intraepithelial lesion (LSIL)/CIN1] or atypical squamous cells [atypical squamous cells of undetermined significance (ASC-US)/atypical squamous cells- cannot exclude high-grade squamous intraepithelial lesion (ASC-H)] require active surveillance for disease progression. A safe and effective immunotherapy to clear HPV16 is an unmet medical need. This study (NCT03911076) is a randomized double-blind, placebo-controlled phase II trial of PVX2 [vaccination twice with HPV16-targeting pNGVL4a-Sig/E7(detox)/HSP70 plasmid and once with the HPV16 L2E7E6 fusion protein "TA-CIN"] as immunotherapy for patients with HPV16+ ASC-US, ASC-H, or LSIL/CIN1. The primary objective of this cohort is to determine the safety and tolerability of PVX2 in three monthly immunizations. Subjects are confirmed to have HPV16 infection and LSIL/CIN1, ASC-US, or ASC-H. Adverse events are evaluated using Common Terminology Criteria for Adverse Events v5.0. HPV typing by HPV16 18/45 Aptima Assay is performed at baseline, month 6, and month 12, with simultaneous cytology analysis. Cervical biopsies and endocervical curettage are performed at baseline and month 6. In a safety run-in cohort 12 eligible patients are enrolled prior to the randomized phase.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Safety run-in is open label (no control), followed by randomized double-blind, placebo-controlled study
入排标准
- 年龄范围
- 25 Years 至 70 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Female subjects age 25-70 years with confirmation of ASC-US, ASC-H, or LSIL by liquid-based cytology
- •HIV uninfected
- •Patients whose cytologic specimen is HPV16+ by Aptima HPV 16 18/45 Genotype Assay
- •Body Mass Index ≤ 32 kg/m2
- •Hepatitis B surface antigen negative
- •Anti-hepatitis C virus antibody (anti-HCV) negative or negative HCV PCR if anti-HCV positive
- •Patients who are able and willing to comply with all study procedures and voluntarily sign an informed consent form, and with anticipated availability for the planned follow-up period of one year
- •Patients who are of childbearing potential agree to remain sexually abstinent, use methods of contraception (e.g. oral contraception, barrier methods, spermicide, intrauterine device (IUD)), or have a partner who is sterile (i.e., vasectomy) through 6 months.
- •Patients must have adequate organ function at the time of enrollment as defined by the following parameters: white blood cell count >3,000/mcL; lymphocyte number >500/mcL; absolute neutrophil count >1,000/mcL; platelets >90,000/mcL; hemoglobin >9 g/dL; total bilirubin <3 X the institutional limit of normal; aspartate aminotransferase (AST [SGOT]) / alanine aminotransferase (ALT [SGPT]) <3 X the institutional limit of normal; creatinine <2.5X the institutional limit of normal.
- •Histologic diagnosis of <CIN2 upon screening colposcopic examination with mandatory ECC, and cervical biopsy(ies) as clinically indicated.
排除标准
- •Patients who are attempting pregnancy within 6 months, pregnant, or breastfeeding.
- •Patients with immunodeficiency, or treatment with immunosuppressive medications
- •Administration of any blood product within 3 months of enrollment.
- •Administration of any licensed vaccine within 2 weeks of enrollment (4weeks for measles vaccine)
- •Participation in a study with an investigational compound or device within 30 days of signing informed consent.
- •History of seizures (unless seizure free for 5 years)
- •Patients with positive serological test for human immunodeficiency virus (HIV).
- •Previous cancer history within the past 5 years.
- •Patients who have had chemotherapy, radiation, biological cancer therapy, or other investigational agents within 28 days prior to the first dose of study drug.
- •Patients who have had surgery within 28 days, excluding minor procedures (dental work, skin biopsy, etc).
- •Patients with an uncontrolled intercurrent illness including, but not limited to, ongoing, or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- •Patients who have an active autoimmune disease (e.g., rheumatoid arthritis, systemic lupus erythematosus (SLE), ulcerative colitis, Crohn's Disease, multiple sclerosis (MS), ankylosing spondylitis).
- •Patients with a recognized immunodeficiency disease including cellular immunodeficiencies, hypogammaglobulinemia, or dysgammaglobulinemia; patients who have acquired, hereditary, or congenital immunodeficiencies; patients being chronically treated with immunosuppressive drugs such as cyclosporin, adrenocorticotropic hormone (ACTH), or systemic corticosteroids
- •Previous cervical conization or LEEP procedure or previous total hysterectomy due to cervical lesions at enrollment.
结局指标
主要结局
Incidence of Treatment-Emergent Adverse Events as assessed by CTCAE v5.0
时间窗: 12 months
To evaluate the safety and tolerability of the dual IM pNGVL4a Sig/E7(detox)/HSP70 DNA and single IM TA-CIN immunization regimen
Percent of patients that have cleared HPV16 at Month 6
时间窗: 6 months
To evaluate the efficacy of dual IM pNGVL4a-Sig/E7(detox)/HSP70 DNA and single IM TA-CIN immunization regimen on Human Papillomavirus (HPV) 16 clearance by Month 6
次要结局
- Percent of patients that have normal cytology at Month 6(6 months)
- Percent of patients that have cleared HPV16 at Month 12(12 months)