A vaccine and a device used together to treat women with precancerous cells on the cervix caused by human papillomavirus (HPV).

Phase 1

• Conditions: HPV-16 AND/OR HPV-18 RELATED HIGH GRADE SQUAMOUS INTRAEPITHELIAL LESIONS (HSIL) OF THE CERVIX; MedDRA version: 21.1 Level: PT Classification code 10064328 Term: Human papilloma virus test positive System Organ Class: 10022891 - Investigations; MedDRA version: 21.1 Level: LLT Classification code 10066237 Term: Cervical high grade squamous intraepithelial lesion System Organ Class: 100000004872; Therapeutic area: Diseases [C] - Virus Diseases [C02]

• Registration Number: EUCTR2016-002761-63-FI
• Lead Sponsor: Inovio Pharmaceuticals, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2017-07-26
• Last Update Posted: 11 March 2020

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: Not specified
• Target Recruitment: 198

Inclusion Criteria

Each subject must meet all of the following criteria to be enrolled in the study:
1. Women aged 18 years and above and meets the minimum age of consent per local regulations;
2. Confirmed cervical infection with HPV types 16 and/or 18 at screening by cobasTM 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) Is post-menopausal as defined by spontaneous amenorrhea for more than 12 months
b) Is surgically sterile due to absence of ovaries or due to a bilateral tubal ligation/occlusion performed more than 12 months prior to screening
c) 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:
i. 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).
ii. Abstinence from penile-vaginal intercourse when this is the subject’s preferred and usual lifestyle
iii. Intrauterine device or intrauterine system
iv. 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) no
F.1.3.1 Number of subjects for this age range 10

Exclusion Criteria

Subjects meeting any of the following criteria will be excluded from enrollment in the study:
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 a potentially untreated carcinoma, untreated HSIL, indeterminate, or insufficient for diagnosis (ECC is not required to be 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 visit;
6. History of previous therapeutic HPV vaccination (licensed prophylactic HPV vaccines are allowed, e.g. Gardasil™, Silgard ™, 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 within 45 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 45 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 (i.e. medically significant unintentional weight loss, kwashiorkor, or marasmus) based on screening labs, medical history and physical exam per the investigator’s clinical judgment.
9. Receipt of any non-study, non-live vaccine within 2 weeks of dosing;
10. Receipt of any non-study, live vaccine (e.g. measles vaccine) within 4 weeks of 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 of screening (with the exception of curatively treated, localized anogenit

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified