E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Cervical Intraepithelial Neoplasia (CIN) 2/3 or 3 |
|
E.1.1.1 | Medical condition in easily understood language |
Pre-cancerous cells on the cervix |
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E.1.1.2 | Therapeutic area | Diseases [C] - Female diseases of the urinary and reproductive systems and pregancy complications [C13] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10008263 |
E.1.2 | Term | Cervical dysplasia |
E.1.2 | System Organ Class | 10038604 - Reproductive system and breast disorders |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the histologic response to three 6 mg doses of VGX-3100 administered by IM injection in combination with EP delivered by CELLECTRA®-5P in adult females with biopsy-proven HPV-16 or 18 associated CIN 2/3 or CIN 3 |
|
E.2.2 | Secondary objectives of the trial |
To evaluate the virologic response to three 6 mg doses of VGX-3100 administered by IM injection in combination with EP delivered by CELLECTRA®-5P in adult females with biopsy-proven HPV-16 or 18 associated CIN 2/3 or CIN 3 |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
a. Female subjects age 18-55 years;
b. Histologically confirmed HPV-16 or HPV-18-associated CIN 2/3 or CIN 3 from tissue collected less than 10 weeks prior to Vaccination/EP #1 with no evidence of invasive
cancer in any specimen;
c. Colposcopy is satisfactory based on visualization of the entire squamocolumnar junction and the upper limit of the entire aceto-white or suspected CIN disease area; lesions in ≤ 3 cervical quadrants (4 quadrant disease where the lesion occupies less than 50% of each quadrant will be considered for inclusion);
d. Healthy subjects as judged by the Investigator based on medical history, PE, and normal results for an ECG, CBC, Serum Chemistries, CPK and urinalysis done up to 4 weeks prior to enrollment and administration of study drug;
e. Women of child-bearing potential agree to remain sexually abstinent, use two medically effective methods of contraception (e.g. oral contraception, barrier methods, spermicide, intrauterine device (IUD)), or have a partner who is sterile (i.e., vasectomy) through 36 weeks (9 months);
f. Able and willing to comply with all study procedures and voluntarily signs informed consent form. |
|
E.4 | Principal exclusion criteria |
a. Unsatisfactory colposcopy defined as incomplete visualization of the entire squamocolumnar junction and the upper limit of the entire aceto-white or suspected CIN disease area;
b. Pregnancy or breastfeeding;
c. Immunosuppression including any concurrent condition requiring the continued use of systemic or topical steroids at or near the injection site [deltoid, upper arm] (excluding inhaled and eye drop-containing corticosteroids) or the use of immunosuppressive agents. All other corticosteroids must be discontinued > 4 weeks prior to Day 0 of study vaccine administration; autoimmune disorders, transplant recipients;
d. History of previous therapeutic HPV vaccination (individuals who have been immunized with licensed prophylactic HPV vaccines (e.g. Gardasil®, Cervarix®) are not excluded);
e. Positive serological test for hepatitis C virus or hepatitis B virus surface antigen (HBsAg) or human immunodeficiency virus (HIV);
f. Administration of any blood product within 3 months of enrollment;
g. Administration of any licensed vaccine within 2 weeks of enrollment (4 weeks for measles vaccine);
h. Participation in a study with an investigational compound or device within 30 days of signing informed consent;
i. Cardiac pre-excitation syndromes (such as Wolff-Parkinson-White);
j. History of seizures (unless seizure free for 5 years);
k. Tattoos, scars, or active lesions/rashes within 2 cm of the intended site of vaccination/EP or any implantable leads;
l. Active drug or alcohol use or dependence that, in the opinion of the investigator, would interfere with adherence to study requirements;
m. Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (i.e. infections disease) illness must not be enrolled into this study;
n. Any other conditions judged by the investigator that would limit the evaluation of a subject. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Histopathological regression of cervical lesions to CIN 1 or less |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
Clearance of HPV-16 or 18 in combination with histopathological regression of cervical lesions to CIN 1 or less |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 9 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Canada |
Georgia |
India |
Romania |
South Africa |
United States |
|
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
Last visit of the last subject enrolled |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |