Clinical trial NCT03499795: 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Anal Neoplasm
Keywords: High-grade squamous intraepithelial lesions (HSIL)
Human papillomavirus (HPV)
HPV-16
HPV-18
Anal intraepithelial neoplasia 2 (AIN2)
Anal intraepithelial neoplasia 3 (AIN3)
Peri-anal intraepithelial neoplasia 2 (PAIN2)
Peri-anal intraepithelial neoplasia 3 (PAIN3)
Lead sponsor: Inovio Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2018-04-17
Enrollment: 23
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of Participants With no Histologic Evidence of Anal or Anal/Peri-Anal HSIL and no Evidence of HPV-16/18 at Week 36
timeFrame: Week 36
Secondary outcomes:
measure: Number of Participants With at Least One Local and Systemic Treatment-emergent Adverse Event (TEAE) During 7 Days Following Each Dose
timeFrame: 7 days following each dose: Day 0 (Days 0 to 7), Week 4 (Days 22 to 28), Week 12 (Days 78 to 84), and Week 40 (Days 274 to 280)
measure: Number of Participants With at Least One Adverse Event (AE)
timeFrame: From first injection up to Week 88
measure: Percentage of Participants With no Evidence of Anal or Anal/Peri-Anal HSIL at Week 36
timeFrame: Week 36
measure: Percentage of Participants With no Evidence of HPV-16/18 From Intra-Anal and/or Peri-Anal Tissue by Type-Specific HPV Testing at Week 36
timeFrame: Week 36
measure: Percentage of Participants With no Evidence of HPV-16/18 From Intra-Anal Swab by Specific HPV Testing at Week 36
timeFrame: Week 36
measure: Percentage of Participants With no Evidence of Anal or Anal/Peri-Anal Low-Grade Squamous Intraepithelial Lesion (LSIL) or HSIL at Week 36
timeFrame: Week 36
measure: Percentage of Participants With no Progression of Anal or Anal/Peri-Anal HSIL to Carcinoma From Baseline to Week 36
timeFrame: From Baseline to Week 36
measure: Percent Change From Baseline in the Number of Intra-Anal and/or Peri-Anal Lesions as Determined by the Investigator at Weeks 36, 64, and 88
timeFrame: From Baseline to Weeks 36, 64, and 88
measure: Mean Change From Baseline in Frequency of HPV-16/17 E6/E7-specific CD8+/CD137+ Peripheral Blood Mononuclear Cells (PBMCs) That Were Perforin Positive at Week 15
timeFrame: Baseline and Week 15
measure: Percentage of Participants With no Histologic Evidence of Anal or Anal/Peri-Anal HSIL or no Evidence of HPV-16/18 at Week 36
timeFrame: Week 36
Other outcomes:
measure: Percent Change From Baseline in the Size of Peri-Anal Lesions as Determined by the Investigator at Weeks 36, 64, and 88
timeFrame: From Baseline to Weeks 36, 64, and 88
Locations:
city: Chicago
country: United States
facility: Howard Brown Health (HBH)-Sheridan
state: Illinois
city: New York
country: United States
facility: Laser Surgery Care
state: New York
city: Québec
country: Canada
facility: Clinique de Recherche en Sante
state: Quebec
Study officials:
affiliation: Inovio Pharmaceuticals
name: Jeffrey Skolnik, MD
role: STUDY_DIRECTOR
References: