High Grade Squamous Intraepithelial Lesion of the Cervix
Conditions
Interventions
Test Group:6 mg (1 ml) VGX-3100 intramuscular injection followed by EP with the CELLECTRA 5PSP device given at Day 1, Week 4 and Week 12.
Control Group:Placebo intramuscular injection followed by EP with the CELLECTRA 5PSP device given at Day 1, Week 4 and Week 12.
Sponsors
Chinese Academy of Medical Sciences Cancer Hospital
Eligibility
Sex/Gender
Female
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1.Women aged 18 years and above that meet the minimum age of consent per Chinese regulations; 2.Confirmed cervical infection with HPV types 16 and/or 18 at screening by HPV test; 3.Histologic evidence of cervical HSIL as confirmed by Pathological Adjudication Committee (PAC) at screening; 4.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 an Informed Consent Form (ICF) prior to study- related activities; 5.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; 6.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; 7.Cervical lesion that is accessible for sampling by biopsy instrument (e.g. Mini-Tischler device); 8.Cervical lesion of adequate size to ensure that a visible lesion remains after screening biopsy; 9.Must meet one of the following criteria with respect to their reproductive capacity: (1) Post-menopausal as defined by spontaneous amenorrhea for more than 12 months (2) Surgically sterile due to absence of ovaries or due to a bilateral tubal ligation/occlusion performed more than 12 months prior to screening; (3) 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 signing ICF until visit week 40. The following methods are acceptable: 1) 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); 2) Subjects may abstinence from heterosexual intercourse; 3) Use condoms, such as accidents (rupture, slip, etc.), need to take emergency contraceptive pills 4) Intrauterine device or intrauterine sustained release system; 5) 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. 10.Normal screening Electrocardiogram (ECG) or screening ECG with no clinically significant findings, as judged by the investigator.
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.ECC that shows indeterminate, or insufficient for HSIL diagnosis (ECC is not required to be performed as part of study screening); 4.Treatment for cervical HSIL within 4 weeks prior to signing ICF; 5.Pregnant, breastfeeding or considering becoming pregnant through week 40 visit; 6.History of previous therapeutic HPV vaccination (licensed prophylactic HPV vaccines are allowed, e.g. Gardasil™, SilgardTM, Cervarix™); 7.Presence of any unresolved abnormal clinical screening laboratory values of Grade 1 or greater per Common Toxicity Criteria for Adverse Events (CTCAE) v 4.03 and deemed clinically significant by the investigator 8 weeks prior to Day 0; 8.Immunosuppression as a result of underlying illness or treatment including: (1) History of or positive serologic test for HIV at screening; (2) Primary immunodeficiencies; (3) Long term use (>= 7 days) of oral or parenteral glucocorticoids at a dose of >=20 mg/day of prednisone equivalent; (use of inhaled, topical, otic and ophthalmic corticosteroids are allowed); (4) Current or anticipated use of disease modifying doses of anti-rheumatic drugs (e.g., azathioprine, cyclophosphamide, cyclosporine, methotrexate), and biologic disease modifying drugs (e.g. infliximab, adalimumab or etanercept); (5) History of solid organ or bone marrow transplantation; (6) 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; (7) Subjects who are malnourished (i.e. medically significant unintentional weight loss) based on medical history, screening labs and physical exam per the investigator’s clinical judgment. 9.Receipt of any non-live vaccine within 2 weeks prior to Dosing; 10.Receipt of any live vaccine (e.g. measles vaccine) within 4 weeks prior to Dosing; 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 systemic treatment for malignancy within 2 years prior to signing ICF (locally treated anogenital malignancy and superficial skin cancers are allowed); 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 prior to 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.Resting pulse rate < 50 bpm (unless attributable to athletic
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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.; | — |
Secondary
| Measure | Time frame |
|---|---|
| Incidence and severity of local and systemic adverse events (AEs) for 7 and 28 days following each investigational treatment and for the duration of the study (i.e., 40 weeks);Incidence and severity of all adverse events (SAEs) (e.g., Serious unexpected serious adverse reaction (SUSAR), Unexpected adverse device effect (UADE)) and Adverse Events of special interest (AESI) for the duration of the study (through Week 88 visit);Proportion of subjects with no evidence of cervical HSIL on histology (i.e., biopsies or excisional treatment) at Week 36 visit;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;Proportion of subjects with no evidence of cervical 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;Proportion of subjects with no evidence of cervical 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;Proportion of subjects with no evidence of cervical HSIL on histology (i.e. biopsy or excisional treatment) or no evidence of HPV-16 and/or HPV-18 in cervical samples by type specific HPV testing at Week 36 visit;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;Levels of serum anti-HPV-16 and anti-HPV-18 antibody concentrations at baseline?Weeks 15 and 36 visits;At baseline, week 15, and week 36 visits, the level of cellular immune response in peripheral blood mononuclear cells (PBMC) was measured using the gamma-interferon-enzyme-linked immunospot assay (IFN-? ELISPOT);Injection success rate of subjects treated by VGX-3100 or placebo delivered by CELLECTRATM 5PSP;Percentage of | — |
Countries
China
Contacts
Public ContactWu Lingying
Chinese Academy of Medical Sciences Cancer Hospital
Outcome results
None listed