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: 20.0Level: PTClassification code 10064328Term: Human papilloma virus test positiveSystem Organ Class: 10022891 - Investigations; MedDRA version: 20.0Level: LLTClassification code 10066237Term: Cervical high grade squamous intraepithelial lesionSystem Organ Class: 100000024086; Therapeutic area: Diseases [C] - Virus Diseases [C02]

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

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2017-08-08
• Last Update Posted: 21 March 2022

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Female
• 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;
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 or spontaneous amenorrhea for 6-12 months with FSH level >40 mIU/mL
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:
- 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 and usual lifestyle
- 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

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. 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 during the study;
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 Toxicity 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.
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 <90 mm Hg or a diastolic blood pressure >95 mm Hg at Screening or Day 0;
16. Resting heart rate <50 bpm (unless attributable to athletic co

Study & Design

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