Trial Outcomes & Findings for 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 (NCT NCT03499795)

NCT ID: NCT03499795

Last Updated: 2023-07-14

Results Overview

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

23 participants

Primary outcome timeframe

Week 36

Results posted on

2023-07-14

Participant Flow

Participants were enrolled at study sites in Canada and the United States from 15 May 2018 to 16 June 2020.

A total of 48 participants were screened out of which 23 were enrolled to receive study drug.

Participant milestones

Participant milestones
Measure	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.
Overall Study STARTED	23
Overall Study Safety Population	23
Overall Study Modified Intent-to-treat (mITT) Population	23
Overall Study COMPLETED	21
Overall Study NOT COMPLETED	2

Reasons for withdrawal

Reasons for withdrawal
Measure	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.
Overall Study Adverse Event	1
Overall Study Lost to Follow-up	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	VGX-3100 n=23 Participants 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.
Age, Continuous	46 years STANDARD_DEVIATION 12 • n=5 Participants
Sex: Female, Male Female	7 Participants n=5 Participants
Sex: Female, Male Male	16 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	6 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	17 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race/Ethnicity, Customized Race · White	16 Participants n=5 Participants
Race/Ethnicity, Customized Race · Other	3 Participants n=5 Participants
Race/Ethnicity, Customized Race · Black or African American	2 Participants n=5 Participants
Race/Ethnicity, Customized Race · Asian	2 Participants n=5 Participants
Region of Enrollment Canada	4 participants n=5 Participants
Region of Enrollment United States	19 participants n=5 Participants

PRIMARY outcome

Timeframe: Week 36

Outcome measures

Outcome measures
Measure	VGX-3100 n=22 Participants 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.
Percentage of Participants With no Histologic Evidence of Anal or Anal/Peri-Anal HSIL and no Evidence of HPV-16/18 at Week 36	9.1 percentage of participants Interval 1.6 to 25.9

SECONDARY outcome

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)

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

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.

Outcome measures

Outcome measures
Measure	VGX-3100 n=23 Participants 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.
Number of Participants With at Least One Local and Systemic Treatment-emergent Adverse Event (TEAE) During 7 Days Following Each Dose	21 Participants

SECONDARY outcome

Timeframe: From first injection up to Week 88

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

Outcome measures

Outcome measures
Measure	VGX-3100 n=23 Participants 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.
Number of Participants With at Least One Adverse Event (AE)	23 Participants

SECONDARY outcome

Timeframe: Week 36

Outcome measures

Outcome measures
Measure	VGX-3100 n=22 Participants 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.
Percentage of Participants With no Evidence of Anal or Anal/Peri-Anal HSIL at Week 36	13.6 percentage of participants Interval 2.9 to 34.9

SECONDARY outcome

Timeframe: Week 36

Outcome measures

Outcome measures
Measure	VGX-3100 n=22 Participants 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.
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	45.5 percentage of participants Interval 24.4 to 67.8

SECONDARY outcome

Timeframe: Week 36

Outcome measures

Outcome measures
Measure	VGX-3100 n=22 Participants 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.
Percentage of Participants With no Evidence of HPV-16/18 From Intra-Anal Swab by Specific HPV Testing at Week 36	31.8 percentage of participants Interval 13.9 to 54.9

SECONDARY outcome

Timeframe: Week 36

Outcome measures

Outcome measures
Measure	VGX-3100 n=22 Participants 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.
Percentage of Participants With no Evidence of Anal or Anal/Peri-Anal Low-Grade Squamous Intraepithelial Lesion (LSIL) or HSIL at Week 36	9.1 percentage of participants Interval 1.1 to 29.2

SECONDARY outcome

Timeframe: From Baseline to Week 36

Outcome measures

Outcome measures
Measure	VGX-3100 n=22 Participants 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.
Percentage of Participants With no Progression of Anal or Anal/Peri-Anal HSIL to Carcinoma From Baseline to Week 36	100 percentage of participants Interval 84.6 to 100.0

SECONDARY outcome

Timeframe: From Baseline to Weeks 36, 64, and 88

Population: 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.

Outcome measures

Outcome measures
Measure	VGX-3100 n=22 Participants 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.
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 Percent Change From Baseline at Week 36	-14.2 percent change Standard Deviation 41.93
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 Percent Change From Baseline at Week 64	-3.3 percent change Standard Deviation 37.91
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 Percent Change From Baseline at Week 88	-40.6 percent change Standard Deviation 46.77

SECONDARY outcome

Timeframe: Baseline and 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.

Outcome measures

Outcome measures
Measure	VGX-3100 n=22 Participants 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.
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	4.491 cells/million T cells + PBMCs Standard Deviation 4.9686

SECONDARY outcome

Timeframe: Week 36

Outcome measures

Outcome measures
Measure	VGX-3100 n=22 Participants 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.
Percentage of Participants With no Histologic Evidence of Anal or Anal/Peri-Anal HSIL or no Evidence of HPV-16/18 at Week 36	50.0 percentage of participants Interval 28.2 to 71.8

OTHER_PRE_SPECIFIED outcome

Timeframe: From Baseline to Weeks 36, 64, and 88

Outcome measures

Outcome data not reported

Adverse Events

VGX-3100

Serious events: 1 serious events

Other events: 23 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	VGX-3100 n=23 participants at risk 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.
Injury, poisoning and procedural complications Ankle Fracture	4.3% 1/23 • From first injection up to Week 88 Safety population included all participants who received at least 1 dose of VGX-3100+EP.

Other adverse events

Other adverse events
Measure	VGX-3100 n=23 participants at risk 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.
Gastrointestinal disorders Nausea	43.5% 10/23 • From first injection up to Week 88 Safety population included all participants who received at least 1 dose of VGX-3100+EP.
Gastrointestinal disorders Proctalgia	21.7% 5/23 • From first injection up to Week 88 Safety population included all participants who received at least 1 dose of VGX-3100+EP.
Gastrointestinal disorders Diarrhoea	13.0% 3/23 • From first injection up to Week 88 Safety population included all participants who received at least 1 dose of VGX-3100+EP.
Gastrointestinal disorders Abdominal pain	8.7% 2/23 • From first injection up to Week 88 Safety population included all participants who received at least 1 dose of VGX-3100+EP.
Gastrointestinal disorders Anal fissure	8.7% 2/23 • From first injection up to Week 88 Safety population included all participants who received at least 1 dose of VGX-3100+EP.
Gastrointestinal disorders Constipation	8.7% 2/23 • From first injection up to Week 88 Safety population included all participants who received at least 1 dose of VGX-3100+EP.
Gastrointestinal disorders Gastritis	8.7% 2/23 • From first injection up to Week 88 Safety population included all participants who received at least 1 dose of VGX-3100+EP.
Gastrointestinal disorders Rectal haemorrhage	8.7% 2/23 • From first injection up to Week 88 Safety population included all participants who received at least 1 dose of VGX-3100+EP.
General disorders Injection site pain	87.0% 20/23 • From first injection up to Week 88 Safety population included all participants who received at least 1 dose of VGX-3100+EP.
General disorders Fatigue	60.9% 14/23 • From first injection up to Week 88 Safety population included all participants who received at least 1 dose of VGX-3100+EP.
General disorders Injection site erythema	30.4% 7/23 • From first injection up to Week 88 Safety population included all participants who received at least 1 dose of VGX-3100+EP.
General disorders Injection site pruritus	26.1% 6/23 • From first injection up to Week 88 Safety population included all participants who received at least 1 dose of VGX-3100+EP.
General disorders Injection site bruising	17.4% 4/23 • From first injection up to Week 88 Safety population included all participants who received at least 1 dose of VGX-3100+EP.
General disorders Injection site haemorrhage	17.4% 4/23 • From first injection up to Week 88 Safety population included all participants who received at least 1 dose of VGX-3100+EP.
General disorders Injection site swelling	17.4% 4/23 • From first injection up to Week 88 Safety population included all participants who received at least 1 dose of VGX-3100+EP.
General disorders Malaise	17.4% 4/23 • From first injection up to Week 88 Safety population included all participants who received at least 1 dose of VGX-3100+EP.
Immune system disorders Seasonal allergy	13.0% 3/23 • From first injection up to Week 88 Safety population included all participants who received at least 1 dose of VGX-3100+EP.
Infections and infestations Upper respiratory tract infection	34.8% 8/23 • From first injection up to Week 88 Safety population included all participants who received at least 1 dose of VGX-3100+EP.
Infections and infestations Bronchitis	8.7% 2/23 • From first injection up to Week 88 Safety population included all participants who received at least 1 dose of VGX-3100+EP.
Infections and infestations COVID-19	8.7% 2/23 • From first injection up to Week 88 Safety population included all participants who received at least 1 dose of VGX-3100+EP.
Infections and infestations Oral herpes	8.7% 2/23 • From first injection up to Week 88 Safety population included all participants who received at least 1 dose of VGX-3100+EP.
Injury, poisoning and procedural complications Arthropod bite	8.7% 2/23 • From first injection up to Week 88 Safety population included all participants who received at least 1 dose of VGX-3100+EP.
Musculoskeletal and connective tissue disorders Myalgia	73.9% 17/23 • From first injection up to Week 88 Safety population included all participants who received at least 1 dose of VGX-3100+EP.
Musculoskeletal and connective tissue disorders Arthralgia	34.8% 8/23 • From first injection up to Week 88 Safety population included all participants who received at least 1 dose of VGX-3100+EP.
Musculoskeletal and connective tissue disorders Muscular weakness	8.7% 2/23 • From first injection up to Week 88 Safety population included all participants who received at least 1 dose of VGX-3100+EP.
Musculoskeletal and connective tissue disorders Pain in extremity	8.7% 2/23 • From first injection up to Week 88 Safety population included all participants who received at least 1 dose of VGX-3100+EP.
Nervous system disorders Headache	65.2% 15/23 • From first injection up to Week 88 Safety population included all participants who received at least 1 dose of VGX-3100+EP.
Nervous system disorders Dizziness	8.7% 2/23 • From first injection up to Week 88 Safety population included all participants who received at least 1 dose of VGX-3100+EP.
Nervous system disorders Hypoaesthesia	8.7% 2/23 • From first injection up to Week 88 Safety population included all participants who received at least 1 dose of VGX-3100+EP.
Reproductive system and breast disorders Erectile dysfunction	13.0% 3/23 • From first injection up to Week 88 Safety population included all participants who received at least 1 dose of VGX-3100+EP.
Respiratory, thoracic and mediastinal disorders Cough	13.0% 3/23 • From first injection up to Week 88 Safety population included all participants who received at least 1 dose of VGX-3100+EP.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	8.7% 2/23 • From first injection up to Week 88 Safety population included all participants who received at least 1 dose of VGX-3100+EP.

Additional Information

Study Director

Inovio Pharmaceuticals

Phone: 267-440-4237

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place