VGX-3100 Delivered Intramuscularly (IM) Followed by Elect... | NCT03499795

Label	Type	Description	Intervention Names
VGX-3100	Experimental	Adult participants who were HIV negative with histologically confirmed anal or anal/peri-anal HSIL associated with HPV-16 and/or 18, received four 6 mg doses of VGX-3100 as an IM injection on Day 0, Week 4, Week 12, and Week 40 followed immediately by EP using the CELLECTRA™ 5PSP device.	Biological: VGX-3100 Device: CELLECTRA™ 5PSP

Name	Type	Description	Arm Group Labels	Other Names
VGX-3100	Biological	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.

Measure	Description	Time Frame
Percentage of Participants With no Histologic Evidence of Anal or Anal/Peri-Anal HSIL and no Evidence of HPV-16/18 at Week 36		Week 36

Measure	Description	Time Frame
Number of Participants With at Least One Local and Systemic Treatment-emergent Adverse Event (TEAE) During 7 Days Following Each Dose	An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can include any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. A TEAE is any AE either reported for the first time or worsening of a pre-existing event after the first dose of study drug.

Measure	Description	Time Frame
Percent Change From Baseline in the Size of Peri-Anal Lesions as Determined by the Investigator at Weeks 36, 64, and 88		From Baseline to Weeks 36, 64, and 88

Eligibility Module

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.

Name	Affiliation	Role
Jeffrey Skolnik, MD	Inovio Pharmaceuticals	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Howard Brown Health (HBH)-Sheridan		Chicago	Illinois	60613	United States
Laser Surgery Care

ID	Title	Description
FG000	VGX-3100	Adult participants who were HIV negative with histologically confirmed anal or anal/peri-anal HSIL associated with HPV-16 and/or 18, received four 6 mg doses of VGX-3100 as an intramuscular (IM) injection on Day 0, Week 4, Week 12, and Week 40 followed immediately by electroporation (EP) using the CELLECTRA™ 5PSP device.

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Jan 22, 2020	Jun 5, 2023

ID	Title	Description
BG000	VGX-3100	Adult participants who were HIV negative with histologically confirmed anal or anal/peri-anal HSIL associated with HPV-16 and/or 18, received four 6 mg doses of VGX-3100 as an IM injection on Day 0, Week 4, Week 12, and Week 40 followed immediately by EP using the CELLECTRA™ 5PSP device.

Units	Counts
Participants	BG00023

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Percentage of Participants With no Histologic Evidence of Anal or Anal/Peri-Anal HSIL and no Evidence of HPV-16/18 at Week 36

Posted

Number

95% Confidence Interval

percentage of participants

Week 36

ID	Title	Description
OG000	VGX-3100	Adult participants who were HIV negative with histologically confirmed anal or anal/peri-anal HSIL associated with HPV-16 and/or 18, received four 6 mg doses of VGX-3100 as an IM injection on Day 0, Week 4, Week 12, and Week 40 followed immediately by EP using the CELLECTRA™ 5PSP device.

Units	Counts
Participants	OG00022

Title

Denominators

Categories

Title	Measurements
	OG0009.1(1.6 to 25.9)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000		Clopper-Pearson	P-value was calculated based on the exact method of Clopper-Pearson and superiority was concluded if the one-sided p-value is <0.05.	0.8633														Superiority

Secondary

Number of Participants With at Least One Local and Systemic Treatment-emergent Adverse Event (TEAE) During 7 Days Following Each Dose

An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can include any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. A TEAE is any AE either reported for the first time or worsening of a pre-existing event after the first dose of study drug.

Safety population included all participants who received at least 1 dose of VGX-3100+EP.

Posted

Count of Participants

Participants

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)

ID	Title	Description
OG000	VGX-3100	Adult participants who were HIV negative with histologically confirmed anal or anal/peri-anal HSIL associated with HPV-16 and/or 18, received four 6 mg doses of VGX-3100 as an IM injection on Day 0, Week 4, Week 12, and Week 40 followed immediately by EP using the CELLECTRA™ 5PSP device.

Units	Counts
Participants

Secondary

Number of Participants With at Least One Adverse Event (AE)

Safety population included all participants who received at least 1 dose of VGX-3100+EP.

Posted

Count of Participants

Participants

From first injection up to Week 88

ID	Title	Description
OG000	VGX-3100	Adult participants who were HIV negative with histologically confirmed anal or anal/peri-anal HSIL associated with HPV-16 and/or 18, received four 6 mg doses of VGX-3100 as an IM injection on Day 0, Week 4, Week 12, and Week 40 followed immediately by EP using the CELLECTRA™ 5PSP device.

Units	Counts
Participants	OG000

Secondary

Percentage of Participants With no Evidence of Anal or Anal/Peri-Anal HSIL at Week 36

Posted

Number

95% Confidence Interval

percentage of participants

Week 36

ID	Title	Description
OG000	VGX-3100	Adult participants who were HIV negative with histologically confirmed anal or anal/peri-anal HSIL associated with HPV-16 and/or 18, received four 6 mg doses of VGX-3100 as an IM injection on Day 0, Week 4, Week 12, and Week 40 followed immediately by EP using the CELLECTRA™ 5PSP device.

Units	Counts
Participants	OG000

Secondary

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

Posted

Number

95% Confidence Interval

percentage of participants

Week 36

ID	Title	Description
OG000	VGX-3100	Adult participants who were HIV negative with histologically confirmed anal or anal/peri-anal HSIL associated with HPV-16 and/or 18, received four 6 mg doses of VGX-3100 as an IM injection on Day 0, Week 4, Week 12, and Week 40 followed immediately by EP using the CELLECTRA™ 5PSP device.

Units	Counts
Participants	OG000

Secondary

Percentage of Participants With no Evidence of HPV-16/18 From Intra-Anal Swab by Specific HPV Testing at Week 36

Posted

Number

95% Confidence Interval

percentage of participants

Week 36

ID	Title	Description
OG000	VGX-3100	Adult participants who were HIV negative with histologically confirmed anal or anal/peri-anal HSIL associated with HPV-16 and/or 18, received four 6 mg doses of VGX-3100 as an IM injection on Day 0, Week 4, Week 12, and Week 40 followed immediately by EP using the CELLECTRA™ 5PSP device.

Units	Counts
Participants	OG000

Secondary

Percentage of Participants With no Evidence of Anal or Anal/Peri-Anal Low-Grade Squamous Intraepithelial Lesion (LSIL) or HSIL at Week 36

Posted

Number

95% Confidence Interval

percentage of participants

Week 36

ID	Title	Description
OG000	VGX-3100	Adult participants who were HIV negative with histologically confirmed anal or anal/peri-anal HSIL associated with HPV-16 and/or 18, received four 6 mg doses of VGX-3100 as an IM injection on Day 0, Week 4, Week 12, and Week 40 followed immediately by EP using the CELLECTRA™ 5PSP device.

Units	Counts
Participants	OG000

Secondary

Percentage of Participants With no Progression of Anal or Anal/Peri-Anal HSIL to Carcinoma From Baseline to Week 36

Posted

Number

95% Confidence Interval

percentage of participants

From Baseline to Week 36

ID	Title	Description
OG000	VGX-3100	Adult participants who were HIV negative with histologically confirmed anal or anal/peri-anal HSIL associated with HPV-16 and/or 18, received four 6 mg doses of VGX-3100 as an IM injection on Day 0, Week 4, Week 12, and Week 40 followed immediately by EP using the CELLECTRA™ 5PSP device.

Units	Counts
Participants	OG000

Secondary

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

mITT population included all participants who received at least 1 dose of VGX-3100+EP. 'Overall number of participants analyzed' indicates the number of participants with data available for outcome measure analysis. 'Number analyzed' indicates the number of participants with data available for analysis at the specified timepoint.

Posted

Mean

Standard Deviation

percent change

From Baseline to Weeks 36, 64, and 88

ID	Title	Description
OG000	VGX-3100	Adult participants who were HIV negative with histologically confirmed anal or anal/peri-anal HSIL associated with HPV-16 and/or 18, received four 6 mg doses of VGX-3100 as an IM injection on Day 0, Week 4, Week 12, and Week 40 followed immediately by EP using the CELLECTRA™ 5PSP device.

Units	Counts
Participants	OG000

Secondary

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

PBMCs were isolated from whole blood samples. The assessment of cellular immune activity occurred via the application Flow Cytometry for the purposes of performing a Lytic Granule Loading Assay. The Lytic Granule Loading assay examined cluster of differentiation (CD)8/CD137 cellular markers and Perforin (proteins involved in lytic degranulation and cytotoxic potential) intracellular marker. The frequency was presented as number of perforin-positive CD8 i.e., CD8+/ CD137+ PBMCs cells per million CD8+/ CD137+ PBMCs cells.

Posted

Mean

Standard Deviation

cells/million T cells + PBMCs

Baseline and Week 15

ID	Title	Description
OG000	VGX-3100	Adult participants who were HIV negative with histologically confirmed anal or anal/peri-anal HSIL associated with HPV-16 and/or 18, received four 6 mg doses of VGX-3100 as an IM injection on Day 0, Week 4, Week 12, and Week 40 followed immediately by EP using the CELLECTRA™ 5PSP device.

Units	Counts
Participants

Secondary

Percentage of Participants With no Histologic Evidence of Anal or Anal/Peri-Anal HSIL or no Evidence of HPV-16/18 at Week 36

Posted

Number

95% Confidence Interval

percentage of participants

Week 36

ID	Title	Description
OG000	VGX-3100	Adult participants who were HIV negative with histologically confirmed anal or anal/peri-anal HSIL associated with HPV-16 and/or 18, received four 6 mg doses of VGX-3100 as an IM injection on Day 0, Week 4, Week 12, and Week 40 followed immediately by EP using the CELLECTRA™ 5PSP device.

Units	Counts
Participants	OG000

Other Pre-specified

Percent Change From Baseline in the Size of Peri-Anal Lesions as Determined by the Investigator at Weeks 36, 64, and 88

Not Posted

From Baseline to Weeks 36, 64, and 88

Participants

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Nausea	Gastrointestinal disorders	MedDRA (23.0)	Systematic Assessment	EG00010 affected23 at risk
Proctalgia	Gastrointestinal disorders	MedDRA (23.0)	Systematic Assessment	EG0005 affected23 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA (23.0)	Systematic Assessment	EG0003 affected23 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA (23.0)	Systematic Assessment	EG0002 affected23 at risk
Anal fissure	Gastrointestinal disorders	MedDRA (23.0)	Systematic Assessment	EG0002 affected23 at risk
Constipation	Gastrointestinal disorders	MedDRA (23.0)	Systematic Assessment	EG0002 affected23 at risk
Gastritis	Gastrointestinal disorders	MedDRA (23.0)	Systematic Assessment	EG0002 affected23 at risk
Rectal haemorrhage	Gastrointestinal disorders	MedDRA (23.0)	Systematic Assessment	EG0002 affected23 at risk
Injection site pain	General disorders	MedDRA (23.0)	Systematic Assessment	EG00020 affected23 at risk
Fatigue	General disorders	MedDRA (23.0)	Systematic Assessment	EG00014 affected23 at risk
Injection site erythema	General disorders	MedDRA (23.0)	Systematic Assessment	EG0007 affected23 at risk
Injection site pruritus	General disorders	MedDRA (23.0)	Systematic Assessment	EG0006 affected23 at risk
Injection site bruising	General disorders	MedDRA (23.0)	Systematic Assessment	EG0004 affected23 at risk
Injection site haemorrhage	General disorders	MedDRA (23.0)	Systematic Assessment	EG0004 affected23 at risk
Injection site swelling	General disorders	MedDRA (23.0)	Systematic Assessment	EG0004 affected23 at risk
Malaise	General disorders	MedDRA (23.0)	Systematic Assessment	EG0004 affected23 at risk
Seasonal allergy	Immune system disorders	MedDRA (23.0)	Systematic Assessment	EG0003 affected23 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA (23.0)	Systematic Assessment	EG0008 affected23 at risk
Bronchitis	Infections and infestations	MedDRA (23.0)	Systematic Assessment	EG0002 affected23 at risk
COVID-19	Infections and infestations	MedDRA (23.0)	Systematic Assessment	EG0002 affected23 at risk
Oral herpes	Infections and infestations	MedDRA (23.0)	Systematic Assessment	EG0002 affected23 at risk
Arthropod bite	Injury, poisoning and procedural complications	MedDRA (23.0)	Systematic Assessment	EG0002 affected23 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA (23.0)	Systematic Assessment	EG00017 affected23 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA (23.0)	Systematic Assessment	EG0008 affected23 at risk
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA (23.0)	Systematic Assessment	EG0002 affected23 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA (23.0)	Systematic Assessment	EG0002 affected23 at risk
Headache	Nervous system disorders	MedDRA (23.0)	Systematic Assessment	EG00015 affected23 at risk
Dizziness	Nervous system disorders	MedDRA (23.0)	Systematic Assessment	EG0002 affected23 at risk
Hypoaesthesia	Nervous system disorders	MedDRA (23.0)	Systematic Assessment	EG0002 affected23 at risk
Erectile dysfunction	Reproductive system and breast disorders	MedDRA (23.0)	Systematic Assessment	EG0003 affected23 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA (23.0)	Systematic Assessment	EG0003 affected23 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA (23.0)	Systematic Assessment	EG0002 affected23 at risk

ID	Term
D001005	Anus Neoplasms
D000081483	Squamous Intraepithelial Lesions

ID	Term
D012004	Rectal Neoplasms
D015179	Colorectal Neoplasms
D007414	Intestinal Neoplasms
D005770	Gastrointestinal Neoplasms
D004067	Digestive System Neoplasms
D009371	Neoplasms by Site
D009369	Neoplasms
D004066	Digestive System Diseases
D005767	Gastrointestinal Diseases
D007410	Intestinal Diseases
D001004	Anus Diseases
D012002	Rectal Diseases
D065308	Morphological and Microscopic Findings
D013568	Pathological Conditions, Signs and Symptoms