VGX-3100 Delivered Intramuscularly (IM) Followed by Electroporation (EP) for the Treatment of HPV-16 and/or HPV-18 Related Anal or Anal/Peri-Anal, High Grade Squamous Intraepithelial Lesion (HSIL) in Individuals Seronegative for Human Immunodeficiency Virus (HIV)-1/2

Sponsor

Inovio Pharmaceuticals (Industry)

Overall Status

Completed

CT.gov ID

NCT03499795

Collaborator

(none)

Enrollment

Locations

Arm

36.7

Actual Duration (Months)

7.3

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a phase 2, open-label efficacy study of VGX-3100 administered by intramuscular (IM) injection followed by electroporation (EP) in adult men and women who are human immunodeficiency virus (HIV) negative with histologically confirmed anal or anal/peri-anal high-grade squamous intraepithelial lesion (HSIL) associated with human papilloma virus (HPV)-16 and/or HPV-18. Approximately 24 participants will receive at least 3 doses of VGX-3100.

Condition or Disease	Intervention/Treatment	Phase
Anal Neoplasm	Biological: VGX-3100 Device: CELLECTRA™ 5PSP	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

22 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 2, Open Label, Study of VGX-3100 Delivered Intramuscularly (IM) Followed by Electroporation (EP) for the Treatment of HPV-16 and/or HPV-18 Related Anal or Anal/Peri-Anal, High Grade Squamous Intraepithelial Lesion (HSIL), (AIN2, AIN3, PAIN2, PAIN3) in Individuals That Are Seronegative for Human Immunodeficiency Virus (HIV)-1/2

Actual Study Start Date :

May 3, 2018

Actual Primary Completion Date :

Jun 16, 2020

Actual Study Completion Date :

May 25, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: VGX-3100 Adult participants, who are HIV negative with histologically confirmed anal or anal/peri-anal HSIL associated with HPV-16 and/or 18, will receive VGX-3100 administered by IM injection followed immediately by EP using the CELLECTRA™ 5PSP device. Participants will receive at least 3 doses of VGX-3100 at Day 0, Week 4 and Week 12. For partial responders at Week 36, a fourth dose may be administered at Week 40. All participants are scheduled to be followed to Week 88.	Biological: VGX-3100 One milliliter (1 mL) VGX-3100 (deoxyribonucleic acid [DNA] plasmids encoding E6 and E7 proteins of HPV types 16 and 18) will be injected IM and delivered by EP using CELLECTRA™ 5PSP on Day 0, Week 4 and Week 12, and potentially Week 40. Device: CELLECTRA™ 5PSP IM injection of VGX-3100 is followed by EP with the CELLECTRA™ 5PSP device.

Arm

Intervention/Treatment

Experimental: VGX-3100

Adult participants, who are HIV negative with histologically confirmed anal or anal/peri-anal HSIL associated with HPV-16 and/or 18, will receive VGX-3100 administered by IM injection followed immediately by EP using the CELLECTRA™ 5PSP device. Participants will receive at least 3 doses of VGX-3100 at Day 0, Week 4 and Week 12. For partial responders at Week 36, a fourth dose may be administered at Week 40. All participants are scheduled to be followed to Week 88.

Biological: VGX-3100

One milliliter (1 mL) VGX-3100 (deoxyribonucleic acid [DNA] plasmids encoding E6 and E7 proteins of HPV types 16 and 18) will be injected IM and delivered by EP using CELLECTRA™ 5PSP on Day 0, Week 4 and Week 12, and potentially Week 40.

Device: CELLECTRA™ 5PSP

IM injection of VGX-3100 is followed by EP with the CELLECTRA™ 5PSP device.

Outcome Measures

Primary Outcome Measures

Percentage of Participants with No Histologic Evidence of Anal or Anal/Peri-Anal HSIL and No Evidence of HPV-16/18 at Week 36 [At Week 36]

Secondary Outcome Measures

Number of Local and Systemic Safety Events During 7 Days Following Each Dose [Days 0-7 (7 days following Day 0 dose), Days 22-29 (7 days following Week 4 dose) and Days 78-85 (7 days following Week 12 dose)]
Number of Adverse Events [From baseline to the Week 88 visit]
Percentage of Participants with No Evidence of Anal or Anal/Peri-Anal HSIL on Histology at the Week 36 visit [At Week 36]
Percentage of Participants with No Evidence of HPV-16/18 from Intra-Anal and/or Peri-Anal Tissue by Type-Specific HPV Testing at the Week 36 Visit [At Week 36]
Percentage of Participants with No Evidence of HPV-16/18 from Intra-Anal Swab by Specific HPV Testing at the Weeks 36, 64, and 88 Visits [At Weeks 36, 64 and 88]
Percentage of Participants with No Evidence of Anal or Anal/Peri-Anal Low-Grade Squamous Intraepithelial Lesion (LSIL) or HSIL on Histology at the Week 36 Visit [At Week 36]
Percentage of Participants with No Progression of Anal or Anal/Peri-Anal HSIL to Carcinoma from Baseline on Histology at the Week 36 Visit [From baseline to Week 36]
Percentage Reduction from Baseline in the Number of Intra-Anal and/or Peri-Anal Lesion(s) as Determined by the Investigator at the Weeks 36, 64 and 88 Visits [From baseline to Weeks 36, 64 and 88]
Percentage Reduction from Baseline in the Size of Peri-Anal Lesion(s) as Determined by the Investigator at the Weeks 36, 64 and 88 Visits [From baseline to Weeks 36, 64 and 88]
Flow Cytometry Response Magnitudes [At baseline and Week 15]
Percentage of Participants with No Histologic Evidence of Anal or Anal/Peri-Anal HSIL or No Evidence of HPV-16/18 at Week 36 [At Week 36]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Negative screening test for HIV-1/2 within 30 days of Dose 1;
Confirmed anal or anal/peri-anal HPV-16/18 infection at Screening by polymerase chain reaction (PCR) from HSIL specimen;
Anal tissue specimen/slides for diagnosis must be collected within 10 weeks of first dose of VGX-3100;
At least one anal or anal/peri-anal (AIN2/3 and/or PAIN2/PAIN3) lesion that is histologically-confirmed as HSIL at Screening;
Appropriate candidate for histology collection procedures (i.e. excision or biopsy) as judged by the Investigator;
Female subjects must be post-menopausal, surgically sterile or agree to avoid pregnancy by continued abstinence or use of a contraceptive method with failure rate of less than 1% per year from Screening to one month after last dose of study medication (Week 12 or Week 40)
Men who could father a child must agree to use at least one form of birth control during or continued abstinence from heterosexual intercourse prior to the study, for the duration of study participation and one month after last dose of study medication.
Normal Screening electrocardiogram (ECG).

Exclusion Criteria:

Untreated micro invasive or invasive cancer;
Biopsy-proven Vaginal Intraepithelial Neoplasia (VAIN) and not undergoing medical care and/or treatment for VAIN;
Biopsy-proven Vulvar Intraepithelial Neoplasia (VIN) and not undergoing medical care and/or treatment for VIN;
Biopsy-proven Cervical Intraepithelial Neoplasia (CIN) 2/3 and not undergoing medical care and/or treatment for CIN;
Biopsy-proven Penile Intraepithelial Neoplasia (PIN) and not undergoing medical care and/or treatment for PIN;
Anal or anal/peri-anal HSIL that is not accessible for sampling by biopsy instrument;
Intra-anal and/or peri-anal lesion(s) that cannot be fully visualized at Screening;
Inability to have complete and satisfactory high resolution anoscopic exams (HRAs)
Any treatment for anal or anal/peri-anal HSIL (e.g. surgery) within 4 weeks of Screening;
Pregnant, breast feeding or considering becoming pregnant within one month following the last dose of study medication;
Presence of any abnormal clinical laboratory values greater than Grade 1 per Common Toxicity Criteria for Adverse Events (CTCAE) version 4.03 within 45 days prior to Day 0 or less than Grade 1 but deemed clinically significant by the Investigator;
Immunosuppression as a result of underlying illness or treatment;
History of previous therapeutic HPV vaccination;
Receipt of any non-study related non-live vaccine within 2 weeks of any VGX-3100 dose;
Receipt of any non-study related live vaccine (e.g. measles vaccine) within 4 weeks of any VGX-3100 dose;
Significant acute or chronic medical illness that could be negatively impacted by the electroporation treated as deemed by the Investigator;
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;
Prior major surgery within 4 weeks of Day 0;
Participation in an interventional study with an investigational compound or device within 4 weeks of signing the ICF;
Any illness or condition that in the opinion of the Investigator may affect the safety of the subject or the evaluation of any study endpoint.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Howard Brown Health (HBH)-Sheridan	Chicago	Illinois	United States	60613
2	Laser Surgery Care	New York	New York	United States	10011
3	Clinique de Recherche en Sante	Québec	Quebec	Canada	G1S2L6