Double-Blind Randomized Phase II Clinical Trial Assessing Administration of pBI-11 Via Electroporation for the Treatment of Patients With HPV16/18+ <CIN2
Overview
- Phase
- Phase 2
- Intervention
- Not specified
- Conditions
- HPV Infection
- Sponsor
- Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
- Enrollment
- 48
- Locations
- 1
- Primary Endpoint
- Safety - Frequency and Severity Local Adverse Events and Abnormalities
- Status
- Not Yet Recruiting
- Last Updated
- last month
Overview
Brief Summary
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.
Detailed Description
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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
Exclusion Criteria
- •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.
Outcomes
Primary Outcomes
Safety - Frequency and Severity Local Adverse Events and Abnormalities
Time Frame: 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
Time Frame: 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
Time Frame: 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
Time Frame: 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
Time Frame: 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
Time Frame: 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
Time Frame: 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
Time Frame: Duration of study, approximately 12 months
Percentage of administration procedures where a device fault is observed.
Reliability -Percentage of Delays
Time Frame: 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.
Secondary Outcomes
- 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)