HPV-16 and/or HPV-18 related high grade squamous intraepithelial lesion (HSIL) of the cervix MedDRA version: 20.1 Level: PT Classification code 10064328 Term: Human papilloma virus test positive System Organ Class: 10022891 - Investigations MedDRA version: 20.0 Level: LLT Classification code 10066237 Term: Cervical high grade squamous intraepithelial lesion System Organ Class: 100000004872
Conditions
Sponsors
Inovio Pharmaceuticals, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Women aged 18 years and above that meet the minimum age of consent per local regulations; 2. Confirmed cervical infection with HPV types 16 and/or 18 at screening by cobas™ HPV test; 3. Cervical tissue specimen/slides provided to Study Pathology Adjudication Committee for diagnosis must be collected within 10 weeks prior to anticipated date of first dose of study drug; 4. Histologic evidence of cervical HSIL as confirmed by PAC at screening; 5. Must understand, agree and be able to comply with the requirements of the protocol. Subjects must be willing and able to provide voluntary consent to participate and sign a Consent Form prior to study-related activities; 6. Must be judged by Investigator to be an appropriate candidate for the protocol-specified procedure (i.e. excision, 4 quadrant biopsy with ECC, or 4-quadrant biopsy) required at Week 36; 7. Satisfactory colposcopy at screening, defined as full visualization of the squamo-columnar junction (Type I or II transformation zone) and complete visualization of the upper limit of aceto-white epithelium or suspected CIN disease; 8. Cervical lesion that is accessible for sampling by biopsy instrument (e.g. Mini-Tischler device); 9. Cervical lesion of adequate size to ensure that a visible lesion remains after screening biopsy; 10. Must meet one of the following criteria with respect to their reproductive capacity: a) Post-menopausal as defined by spontaneous amenorrhea for more than 12 months; b) Surgically sterile due to absence of ovaries or due to a bilateral tubal ligation/occlusion performed more than 12 months prior to screening; c) Women of Child Bearing Potential (WOCBP) is willing to use a contraceptive method with failure rate of less than 1% per year when used consistently and correctly from screening until Week 36. The following methods are acceptable : - Hormonal contraception: either combined or progestin-alone including oral contraceptives, injectable, implants, vaginal ring, or percutaneous patches. Hormonal contraceptives must not be used in subjects with a history of hypercoagulability (e.g., deep vein thrombosis, pulmonary embolism); - Abstinence from penile-vaginal intercourse when this is the subject’s preferred mode of sexual activity; - Intrauterine device or intrauterine system; - Male partner sterilization at least 6 months prior to the female subject’s entry into the study, and this male is the sole partner for that subject 11. Normal screening ECG or screening ECG with no clinically significant findings, as judged by the investigator Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 188 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 10
Exclusion criteria
Exclusion criteria: 1. Microscopic or gross evidence of adenocarcinoma-in-situ (AIS), high grade vulvar, vaginal (inclusive of cervical HPV-related lesions that extend into the vaginal vault), or anal intraepithelial neoplasia or invasive cancer in any histopathologic specimen at screening; 2. Cervical lesion(s) that cannot be fully visualized on colposcopy due to extension high into cervical canal at screening; 3. History of ECC which showed cervical HSIL indeterminate, or insufficient for diagnosis (ECC is not performed as part of study screening); 4. Treatment for cervical HSIL within 4 weeks prior to screening; 5. Pregnant, breastfeeding or considering becoming pregnant through week 36; 6. History of previous therapeutic HPV vaccination (licensed prophylactic HPV vaccines are allowed, e.g. Gardasil™, Cervarix™); 7. Presence of any abnormal clinical screening laboratory values greater than Grade 1 per Common Terminology Criteria for Adverse Events (CTCAE) v 4.03 or less than Grade 1 but deemed clinically significant by the investigator within 30 days prior to Day 0; 8. Immunosuppression as a result of underlying illness or treatment including: a) History of or positive serologic test for HIV at screening (performed within 30 days prior to Day 0) b) Primary immunodeficiencies c) Long term use (= 7 days) of oral or parenteral glucocorticoids at a dose of =20 mg/day of prednisone equivalent; (use of inhaled, otic, and ophthalmic corticosteroids are allowed) d) Current or anticipated use of disease modifying doses of anti-rheumatic drugs (e.g., azathioprine, cyclophosphamide, cyclosporine, methotrexate), and biologic disease modifying drugs such as TNF-a inhibitors (e.g. infliximab, adalimumab or etanercept) e) History of solid organ or bone marrow transplantation f) Any prior history of other clinically significant immunosuppressive or clinically diagnosed autoimmune disease that may jeopardize the safety of the subject or require therapy that would interfere with study assessments or endpoint evaluation, or otherwise impact the validity of the study results. g) Subjects who are malnourished based on screening labs, medical history (e.g. clinically significant unintentional weight loss) and physical exam, as determined by investigator clinical judgement 9. Receipt of any non-study, non-live vaccine within 2 weeks of Day 0; 10. Receipt of any non-study, live vaccine (e.g. measles vaccine) within 4 weeks of Day 0; 11. Current or history of clinically significant, medically unstable disease which, in the judgment of the investigator, would jeopardize the safety of the subject, interfere with study assessments or endpoint evaluation, or otherwise impact the validity of the study results (e.g. chronic renal failure; angina, myocardial ischemia or infarction, class 3 or higher congestive heart failure, cardiomyopathy, or clinically significant arrhythmias) 12. Malignancy or treatment for malignancy within 2 years of screening, with the exception of superficial skin cancers that only require local excision; 13. Presence of acute or chronic bleeding or clotting disorder that would contraindicate IM injections, or use of blood thinners (e.g. anticoagulants or antiplatelet drugs) within 2 weeks of Day 0; 14. History of seizures unless seizure free for 5 years with the use of one or fewer antiepileptic agents; 15. Sustained, manually confirmed, sitting systolic blood pressure >150 mm Hg or 95 mm Hg at Screening or Day 0; 16.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Determine the efficacy of VGX-3100 compared with placebo with respect to combined histopathologic regression of cervical HSIL and virologic clearance of HPV-16 and/or HPV-18;Secondary Objective: 1. Evaluate the safety and tolerability of VGX-3100 delivered IM followed by EP with CELLECTRA™ 5PSP 2. Determine VGX-3100 efficacy compared to placebo as measured by histopathologic regression of cervical HSIL 3. Determine VGX-3100 efficacy compared to placebo as measured by virologic clearance of HPV-16 and/or HPV-18 4. Determine VGX-3100 efficacy compared to placebo as measured by complete histopathologic regression of cervical HSIL to normal 5. Determine VGX-3100 efficacy compared to placebo as measured by both complete histopathologic regression of cervical HSIL to normal and virologic clearance of HPV-16 and/or HPV-18 6. Determine VGX-3100 efficacy compared to placebo as measured by histopathologic non-progression 7. Describe the clearance of HPV-16 and/or HPV-18 infection from non-cervical anatomic locations 8. Determine the humoral and cellular immune response of VGX-3100 compared with placebo at post dose 3 and week 36 visit as assessed relative to baseline;Primary end point(s): Proportion of subjects with no evidence of cervical HSIL on histology (i.e. biopsy or excisional treatment) and no evidence of HPV-16 and/or HPV-18 in cervical samples by type specific HPV testing at Week 36 visit;Timepoint(s) of evaluation of this end point: At Week 36 visit | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1a. Incidence and severity of local and systemic events for 7 and 28 days following each investigational treatment and for the duration of the study 40 weeks 1b. Incidence and severity of all adverse events including Serious adverse events (SAEs) (e.g. Serious unexpected serious adverse reaction (SUSAR), Unexpected adverse device effect (UADE) and other unexpected AEs) for the duration of the study (through Week 40 visit) 2. Proportion of subjects with no evidence of cervical HSIL on histology (i.e. biopsies or excisional treatment) at Week 36 visit 3. Proportion of subjects with no evidence of HPV-16 and/or HPV-18 in cervical samples by type specific HPV testing at Week 36 visit 4. Proportion of subjects with no evidence of Low grade squamous intraepithelial lesion (LSIL) or HSIL (i.e. no evidence of CIN1, CIN2 or CIN3) on histology (i.e. biopsies or excisional treatment) at Week 36 visit 5. Proportion of subjects with no evidence of LSIL or HSIL (i.e. no evidence of CIN1, CIN2 or CIN3 on biopsies or excisional treatment) on histology (i.e. biopsies or excisional treatment) and no evidence of HPV-16 and/or HPV-18 by type specific HPV testing at Week 36 visit 6. Proportion of subjects with no progression of cervical HSIL to cervical carcinoma from baseline on histology (i.e. biopsies or excisional treatment) at Week 36 visit 7. Proportion of subjects who have cleared HPV-16 and/or HPV-18 on specimens from non-cervical anatomic locations (oropharynx, vagina and intra-anal) at Week 36 Visit 8a. Levels of serum anti-HPV-16 and anti-HPV-18 antibody concentrations at Weeks 15 and 36 visits 8b. Interferon-? ELISpot response magnitudes at baseline, Weeks 15 and 36 visits 8c. Flow Cytometry response magnitudes at baseline and Week 15 visits;Timepoint(s) of evaluation of this end point: 1a. For 7 and 28 days following each investigational treatment and for the duration of the study 40 weeks 1b. Through Week 40 visit 2. At Week 36 visit 3. At Week 3 | — |
Countries
Argentina, Belgium, Brazil, Canada, Estonia, Finland, Germany, Italy, Lithuania, Mexico, Peru, Philippines, Poland, Portugal, Puerto Rico, Slovakia, South Africa, Spain, Thailand, United Kingdom, United States
Contacts
Public ContactClinical Development
Inovio Pharmaceuticals, Inc.
Outcome results
None listed