Double-Blind Randomized Phase II Clinical Trial Assessing Administration of pBI-11 Via Electroporation for the Treatment of Patients With HPV16/18+ <CIN2
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 48
- 试验地点
- 2
- 主要终点
- Safety - Frequency and Severity Local Adverse Events and Abnormalities
研究概览
简要总结
This research is being done to test the safety and feasibility of an investigational DNA vaccine called pBI-11 and to find out what effects, if any, it has on women with persistent human papillomavirus 16 (HPV16+) and/or human papillomavirus (HPV18+) cervical infection.
The DNA vaccine is designed to promote an immune response to treat disease caused by HPV types 16 and 18, viruses that can cause cervical cancer. The pBI-11 DNA vaccine or a placebo will be administered intramuscularly using the TriGridTM Delivery System.
详细描述
This is a randomized double-blind placebo-controlled phase II study with cross-over design. The primary goal of this study is three-fold; one is to determine the safety and feasibility of two pBI-11 DNA administrations four weeks apart in patients with persistent HPV16 and/or HPV18+ <CIN2, wherein 3.0 mg of the plasmid DNA is delivered via electroporation mediated intramuscular (IM) administration with the TriGrid Delivery System version 2.0 (TDS-IM v2.0); to evaluate the effect of vaccine on HPV16/18 viral DNA clearance; to evaluate the reliability of the device.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Negative for Intraepithelial Lesions (NEIL), Atypical Squamous Cells of Undetermined Significance (ASC-US), or Low-grade Squamous Intraepithelial Lesion (LSIL) determined by cervical cytology
- •HPV16 and/or 18+ by Roche Cobas 4800, Roche Linear Array HPV Genotyping test, or other FDA-approved HPV genotyping test (Co-infections with HPV types other than HPV16/18 are permissible).
- •Age ≥ 18 years
- •Baseline Eastern Cooperative Oncology Group performance status of 0 or 1 at the time of enrollment.
- •Patients must have adequate organ function at the time of enrollment as defined by the following parameters:
- •White blood cell count ≥ 3,000 cells/uL
- •Absolute lymphocyte number ≥ 500 cells/uL
- •Absolute neutrophil count ≥ 1,500 cells/uL
- •Platelets ≥ 90,000 cells/uL
- •Hemoglobulin ≥ 9 g/dL
- •Total bilirubin < 3 X the institutional limit of normal
- •Aspartate Aminotransferase (AST) and Alanine Aminotransferase(ALT) < 3 X the institutional limit of normal
- •Creatinine < 2.5 X the institutional limit of normal
- •Women of child-bearing potential must agree to use long acting contraception (e.g. tubal ligation, intrauterine device or hormonal implant) or two forms of contraception (e.g. barrier method, oral contraceptives) prior to study entry and for 3 months after final vaccination.
- •Ability to understand and the willingness to sign a written informed consent document.
- •Able to adhere to the study visit schedule and other protocol requirements.
排除标准
- •Histologic evidence of CIN2, cervical intraepithelial neoplasia 3 (CIN3), adenocarcinoma in situ or malignancy.
- •Patients with a diagnosis of immunosuppression or active systemic use of immunosuppressive medications such as steroids.
- •Patients who are receiving any other investigational agents within 28 days prior to the first dose of study vaccine.
- •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 with a history of systemic autoimmune disease such as multiple sclerosis or systemic lupus erythematosus (SLE), but exclusive of a history of thyroiditis, psoriasis, Sjogren's, or inflammatory bowel disease.
- •Patients who are pregnant or breast feeding or plan to become pregnant within 12 months of first study treatment.
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to pBI-11 DNA vaccine.
- •Patient with active infection of, or receiving treatment for Human Immunodeficiency Virus (HIV), Hepatitis C Virus (HCV), or Hepatitis B Virus (HBV).
- •History of prior malignancy with disease free interval <5 years; however, individuals with completely resected basal cell or squamous cell carcinoma of the skin within this interval may be enrolled.
- •Participants with metal implant(s) at the site of injection or any electronic stimulation device, such as cardiac demand pacemakers, automatic implantable cardiac defibrillator, nerve stimulators, or deep brain stimulators.
- •Participants with any chronic or active neurologic disorder, including seizures and epilepsy, excluding a single febrile seizure as a child or episode of seizure in pregnancy due to eclampsia.
- •Participants with syncopal episode within 12 months of screening, excluding fainting for a known and unrelated cause such as anemia which has been resolved.
- •Administration of immunoglobulins and/or any blood products within the 120 days preceding study entry or planned administration during the study period.
- •Participants with a skin-fold measurement of the cutaneous and subcutaneous tissue for all eligible injection sites (vastus lateralis muscles with intact lymph drainage) exceeds 50 mm.
- •Participants in whom the ability to observe possible local reactions at the injection site (lateralis region) is, in the opinion of the investigator, unacceptably obscured due to a physical condition or permanent body art.
研究组 & 干预措施
Arm 1: pBI-11 + pBI-11 + pBI-11
Will receive 3 doses of pBI-11 using the TriGrid Delivery System.
干预措施: pBI-11 (3 doses) (Biological)
Arm 2: Placebo + Placebo + pBI-11
Will receive 2 doses of placebo and 1 dose of pBI-11 using the TriGrid Delivery System
干预措施: pBI-11 (1 dose) (Biological)
Arm 2: Placebo + Placebo + pBI-11
Will receive 2 doses of placebo and 1 dose of pBI-11 using the TriGrid Delivery System
干预措施: Placebo (2 doses) (Biological)
结局指标
主要结局
Safety - Frequency and Severity Local Adverse Events and Abnormalities
时间窗: Post-first study vaccination up to 12 months
Count of the frequency and severity of local adverse events and abnormalities per CTCAE 5.0
Safety - Frequency and Severity Systemic Adverse Events and Abnormalities
时间窗: Post-first study vaccination up to 12 months
Count of the frequency and severity of systemic adverse events and abnormalities per CTCAE 5.0
Safety - Frequency and Severity Solicited Local Adverse Events and Abnormalities
时间窗: Through 7 days after each study vaccine
Count of the frequency and severity of solicited local adverse events and abnormalities per CTCAE 5.0
Safety - Frequency and Severity Solicited Systemic Adverse Events and Abnormalities
时间窗: At Week 0 up to 7 days post vaccine, At week 4 up to 7 days post vaccine, At 7 months up to 7 days post vaccine
Count of the frequency and severity of solicited systemic adverse events and abnormalities per CTCAE 5.0.
Pain Scores assessed by Visual Analog Scale
时间窗: Week 0, Week 4, 7 months
The mean and standard deviation of the visual analog scale (VAS) based pain scores reported by the participants on the tolerability questionnaire. Scale range 0-10 with higher scores indicating worse pain.
Acceptability as assessed by survey
时间窗: Week 0, Week 4, 7 months
The percentage of "Yes" responses to the acceptability question posed in the tolerability questionnaire
Percentage of participants with no HPV16/18 detection
时间窗: At 6 months post first study vaccine
Effect of 2 doses of pBI-11 on HPV16/18 clearance. The percentage of participants with no detection of HPV16 or HPV18 in cervical specimens by Roche Cobas test.
Reliability - Percentage of Device Faults
时间窗: Duration of study, approximately 12 months
Percentage of administration procedures where a device fault is observed.
Reliability -Percentage of Delays
时间窗: Duration of study, approximately 12 months
Percentage of administration procedures during which a device fault results in a delay in completion of the administration procedure of \> 15 minutes.
次要结局
- Effect of 3 doses of pBI-11 on HPV16/18 clearance - Percentage of Participants that Exhibit HPV16/18 Positivity (Active arm)(At Month 12 post first study vaccine)
- Effect of 1 dose of pBI-11 on HPV16/18 clearance - Percentage of participants that exhibit HPV16/18 positivity (Placebo arm)(At Month 12 post first study vaccine)
- Levels of HPV16/18 E6/E7-specific T cells(At Week 8 post first study vaccine)
- Changes in Cytopathology(Baseline, 6 months, and 12 months post-first study vaccine)