Clinical Trial Results:
A Prospective, Randomized, Double-Blind, Placebo-Controlled Phase 3 Study of VGX-3100 Delivered Intramuscularly Followed by Electroporation With CELLECTRA™ 5PSP for the Treatment of HPV-16 and/or HPV-18 Related High-Grade Squamous Intraepithelial Lesion (HSIL) of the Cervix
Summary
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EudraCT number |
2016-002761-63 |
Trial protocol |
GB LT FI DE CZ ES PT PL SK BE NL EE IT |
Global end of trial date |
06 Apr 2021
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Results information
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Results version number |
v2(current) |
This version publication date |
24 Jan 2024
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First version publication date |
27 May 2022
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Other versions |
v1 |
Version creation reason |
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Summary report(s) |
Updated CSR synopsis Errata 1 Errata 2 |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
HPV-301
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT03185013 | ||
WHO universal trial number (UTN) |
- | ||
Other trial identifiers |
US IND Number: 13683 | ||
Sponsors
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Sponsor organisation name |
Inovio Pharmaceuticals, Inc.
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Sponsor organisation address |
660 W. Germantown Pike, Suite 110, Plymouth Meeting, United States, PA 19462
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Public contact |
Clinical Development, Inovio Pharmaceuticals, Inc., HPV301ClinicalTeam@inovio.com
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Scientific contact |
Clinical Development, Inovio Pharmaceuticals, Inc., HPV301ClinicalTeam@inovio.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
06 Apr 2021
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
06 Apr 2021
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Global end of trial reached? |
Yes
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Global end of trial date |
06 Apr 2021
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
Determine the efficacy of VGX-3100 compared with placebo with respect to combined histopathologic regression of cervical high-grade squamous intraepithelial lesion (HSIL) and virologic clearance of human papillomavirus (HPV-16) and/or HPV-18.
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Protection of trial subjects |
This protocol was implemented in accordance with the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use harmonised tripartite guideline E6(R2): Good Clinical Practice. Written informed consent was to be obtained from each subject and/or from the subject’s legally authorized representative prior to screening into the clinical trial. Subjects were asked to complete a participant diary card during their clinical trial participation to record local and systemic adverse events for 7 days after each clinical trial treatment. Subjects were provided with the investigator emergency contact information and advised to report all AEs.
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Background therapy |
Subjects might have used supportive medications for management of anxiety and pain due to treatment (topical anesthetic, mild sedative, analgesic). | ||
Evidence for comparator |
Placebo (150 mM sodium chloride and 15 mM sodium citrate) plus electroporation (EP) with CELLECTRA™ 5PSP. | ||
Actual start date of recruitment |
28 Jun 2017
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Long term follow-up planned |
Yes
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Long term follow-up rationale |
Efficacy, Safety | ||
Long term follow-up duration |
17 Months | ||
Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Argentina: 4
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Country: Number of subjects enrolled |
Mexico: 1
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Country: Number of subjects enrolled |
Peru: 2
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Country: Number of subjects enrolled |
Philippines: 1
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Country: Number of subjects enrolled |
South Africa: 16
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Country: Number of subjects enrolled |
Thailand: 12
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Country: Number of subjects enrolled |
United States: 56
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Country: Number of subjects enrolled |
Poland: 7
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Country: Number of subjects enrolled |
Portugal: 6
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Country: Number of subjects enrolled |
Slovakia: 6
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Country: Number of subjects enrolled |
Spain: 13
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Country: Number of subjects enrolled |
United Kingdom: 3
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Country: Number of subjects enrolled |
Belgium: 4
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Country: Number of subjects enrolled |
Estonia: 36
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Country: Number of subjects enrolled |
Finland: 5
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Country: Number of subjects enrolled |
Germany: 3
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Country: Number of subjects enrolled |
Italy: 4
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Country: Number of subjects enrolled |
Lithuania: 22
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Worldwide total number of subjects |
201
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EEA total number of subjects |
106
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
201
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
Subjects took part in the study at 96 study centres in 20 countries from 28 June 2017 to 06 April 2021. | |||||||||||||||||||||||||||||||||
Pre-assignment
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Screening details |
A total of 201 subjects with HPV-16 and/or HPV-18 related HSIL of the cervix were randomised in this study, 138 in VGX-3100 + EP and 63 in Placebo + EP. | |||||||||||||||||||||||||||||||||
Period 1
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Period 1 title |
Treatment Period (overall period)
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Is this the baseline period? |
Yes | |||||||||||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | |||||||||||||||||||||||||||||||||
Roles blinded |
Subject, Investigator, Monitor, Data analyst, Carer | |||||||||||||||||||||||||||||||||
Blinding implementation details |
This clinical trial was double-blinded with blinding maintained throughout the clinical trial by use of identical packaging for both the active product VGX-3100 and the placebo. There was no difference in appearance for both the active product and the placebo. No personnel directly involved with the clinical trial was to be unblinded. The investigator may have requested to unblind a subject’s treatment assignment in case of an emergency or serious medical condition.
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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VGX-3100 + EP | |||||||||||||||||||||||||||||||||
Arm description |
Subjects received three intramuscular (IM) injections of 6 milligram (mg) (in 1 milliliter [mL]) VGX-3100 followed by EP using the CELLECTRA™-5PSP device on Day 0, Week 4, and Week 12. | |||||||||||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||||||||||
Investigational medicinal product name |
VGX-3100
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Injection , Intramuscular use
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Dosage and administration details |
6-mg dose of VGX-3100 drug product was delivered IM followed by EP. VGX-3100 drug product was provided as a solution containing 6 mg in 150 mM sodium chloride and 15 mM sodium citrate. The IP was delivered using the CELLECTRA™ 5PSP device. The device consisted of the following components: 1) Base Station; 2) Handset; and 3) Sterile single-use Array (for accepting the IP cartridge). The first clinical trial treatment was administered on Day 0, the second at Week 4, and the third (final) at Week 12.
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Arm title
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Placebo + EP | |||||||||||||||||||||||||||||||||
Arm description |
Subjects received three IM injections of 1 mL VGX-3100 matching placebo followed by EP using the CELLECTRA™-5PSP device on Day 0, Week 4, and Week 12. | |||||||||||||||||||||||||||||||||
Arm type |
Placebo + EP | |||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Injection , Intramuscular use
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Dosage and administration details |
Subjects received 1 mL placebo IM followed by EP. Placebo was delivered using the CELLECTRA™ 5PSP device. The device consisted of the following components: 1) Base Station; 2) Handset; and 3) Sterile single-use Array (for accepting the IP cartridge). The first clinical trial treatment was administered on Day 0, the second at Week 4, and the third (final) at Week 12.
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Baseline characteristics reporting groups
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Reporting group title |
VGX-3100 + EP
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Reporting group description |
Subjects received three intramuscular (IM) injections of 6 milligram (mg) (in 1 milliliter [mL]) VGX-3100 followed by EP using the CELLECTRA™-5PSP device on Day 0, Week 4, and Week 12. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo + EP
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Reporting group description |
Subjects received three IM injections of 1 mL VGX-3100 matching placebo followed by EP using the CELLECTRA™-5PSP device on Day 0, Week 4, and Week 12. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
Intent-to-Treat (ITT)
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Subject analysis set type |
Intention-to-treat | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Intent-to-Treat (ITT) population included all subjects who were randomized.
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Subject analysis set title |
Modified ITT (mITT)
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Subject analysis set type |
Modified intention-to-treat | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Modified Intent-to-Treat (mITT) population included all subjects who received at least one (1) dose of clinical trial treatment and who had the analysis endpoint of interest.
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Subject analysis set title |
Per-Protocol (PP) Set
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Subject analysis set type |
Per protocol | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Per-Protocol (PP) Set was comprised of subjects who received all doses of clinical trial treatments, had no protocol violations, and had the analysis endpoint of interest.
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Subject analysis set title |
Safety Set
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Subject analysis set type |
Safety analysis | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
The safety set included all subjects who received at least one (1) dose of clinical trial treatment.
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End points reporting groups
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Reporting group title |
VGX-3100 + EP
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Reporting group description |
Subjects received three intramuscular (IM) injections of 6 milligram (mg) (in 1 milliliter [mL]) VGX-3100 followed by EP using the CELLECTRA™-5PSP device on Day 0, Week 4, and Week 12. | ||
Reporting group title |
Placebo + EP
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Reporting group description |
Subjects received three IM injections of 1 mL VGX-3100 matching placebo followed by EP using the CELLECTRA™-5PSP device on Day 0, Week 4, and Week 12. | ||
Subject analysis set title |
Intent-to-Treat (ITT)
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Subject analysis set type |
Intention-to-treat | ||
Subject analysis set description |
Intent-to-Treat (ITT) population included all subjects who were randomized.
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Subject analysis set title |
Modified ITT (mITT)
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Subject analysis set type |
Modified intention-to-treat | ||
Subject analysis set description |
Modified Intent-to-Treat (mITT) population included all subjects who received at least one (1) dose of clinical trial treatment and who had the analysis endpoint of interest.
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Subject analysis set title |
Per-Protocol (PP) Set
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
Per-Protocol (PP) Set was comprised of subjects who received all doses of clinical trial treatments, had no protocol violations, and had the analysis endpoint of interest.
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Subject analysis set title |
Safety Set
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
The safety set included all subjects who received at least one (1) dose of clinical trial treatment.
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End point title |
Percentage of Subjects With No Evidence of Cervical HSIL on Histology and No Evidence of HPV-16 and/or HPV-18 in Cervical Samples | ||||||||||||
End point description |
Subjects with no histologic (i.e., biopsies or excisional treatment) evidence of cervical HSIL, no evidence of HPV-16 and/or HPV-18 at the Week 36 time frame, and subjects in which excision or biopsy sample was not obtained between the initial dose up to Week 36 were considered to be responders. No evidence of HSIL was defined by histology as negative, squamous atypia, or low-grade intraepithelial lesion (LSIL). Cervical samples for HPV-16 and/or HPV-18 were collected using the ThinPrep®. ITT population included all subjects who were randomised.
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End point type |
Primary
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End point timeframe |
Week 36
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Statistical analysis title |
Statistical Analysis | ||||||||||||
Statistical analysis description |
Superiority was concluded if the one-sided p-value was <0.025 and the corresponding lower bound of the 95% confidence interval (CI) exceeded zero (0).
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Comparison groups |
VGX-3100 + EP v Placebo + EP
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Number of subjects included in analysis |
201
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
= 0.029 [1] | ||||||||||||
Method |
Miettinen and Nurminen | ||||||||||||
Parameter type |
Difference in percentage | ||||||||||||
Point estimate |
11.4
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
-0.4 | ||||||||||||
upper limit |
21.2 | ||||||||||||
Notes [1] - One-sided p-value |
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End point title |
Histopathological Regression of Cervical HSIL and Virologic Clearance of HPV-16 and/or HPV-18 at Week 36 (mITT Population) | |||||||||||||||||||||
End point description |
Subjects with no histologic (i.e., biopsies or excisional treatment) evidence of cervical HSIL, no evidence of HPV-16 and/or HPV-18 at the Week 36 time frame, and subjects in which excision or biopsy sample was not obtained between the initial dose up to Week 36 were considered to be responders. No evidence of HSIL was defined by histology as negative, squamous atypia, or low-grade intraepithelial lesion (LSIL). Cervical samples for HPV-16 and/or HPV-18 were collected using the ThinPrep®. mITT population included all subjects who received at least one (1) dose of clinical trial treatment and who had the analysis endpoint of interest. Analyses of primary efficacy endpoint with the mITT set served as sensitivity analyses and were considered supportive of the corresponding analysis with the ITT set.
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End point type |
Primary
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End point timeframe |
Week 36
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Statistical analysis title |
Statistical Analysis | |||||||||||||||||||||
Statistical analysis description |
Superiority was concluded if the one-sided p-value was <0.025 and the corresponding lower bound of the 95% CI exceeded zero (0).
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Comparison groups |
VGX-3100 + EP v Placebo + EP
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Number of subjects included in analysis |
197
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Analysis specification |
Pre-specified
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Analysis type |
superiority | |||||||||||||||||||||
P-value |
= 0.022 [2] | |||||||||||||||||||||
Method |
Miettinen and Nurminen | |||||||||||||||||||||
Parameter type |
Risk difference (RD) | |||||||||||||||||||||
Point estimate |
12.4
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Confidence interval |
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level |
95% | |||||||||||||||||||||
sides |
2-sided
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lower limit |
0.4 | |||||||||||||||||||||
upper limit |
22.5 | |||||||||||||||||||||
Notes [2] - One-sided p-value |
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End point title |
Histopathological Regression of Cervical HSIL and Virologic Clearance of HPV-16 and/or HPV-18 at Week 36 (PP Population) | |||||||||||||||||||||
End point description |
Subjects with no histologic (i.e., biopsies or excisional treatment) evidence of cervical HSIL, no evidence of HPV-16 and/or HPV-18 at the Week 36 time frame, and subjects in which excision or biopsy sample was not obtained between the initial dose up to Week 36 were considered to be responders. No evidence of HSIL was defined by histology as negative, squamous atypia, or low-grade intraepithelial lesion (LSIL). Cervical samples for HPV-16 and/or HPV-18 were collected using the ThinPrep®. PP Set was comprised of subjects who received all doses of clinical trial treatments, had no protocol violations, and had the analysis endpoint of interest. Analyses of primary efficacy endpoint with the PP set served as sensitivity analyses and were considered supportive of the corresponding analysis with the ITT set.
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End point type |
Primary
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End point timeframe |
Week 36
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Statistical analysis title |
Statistical Analysis | |||||||||||||||||||||
Statistical analysis description |
Superiority was concluded if the one-sided p-value was <0.025 and the corresponding lower bound of the 95% CI exceeded zero (0).
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Comparison groups |
Placebo + EP v VGX-3100 + EP
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Number of subjects included in analysis |
184
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Analysis specification |
Pre-specified
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Analysis type |
superiority | |||||||||||||||||||||
P-value |
= 0.021 [3] | |||||||||||||||||||||
Method |
Miettinen and Nurminen | |||||||||||||||||||||
Parameter type |
Risk difference (RD) | |||||||||||||||||||||
Point estimate |
12.9
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Confidence interval |
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level |
95% | |||||||||||||||||||||
sides |
2-sided
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lower limit |
0.5 | |||||||||||||||||||||
upper limit |
23.5 | |||||||||||||||||||||
Notes [3] - One-sided p-value |
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End point title |
Number of Subjects With Any Adverse Events (AEs) and Serious Adverse Events (SAEs) Following Investigational Treatment for the Duration of the Study | |||||||||||||||
End point description |
An AE is any untoward medical occurrence in a subject administered a pharmaceutical product and which does not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as AEs. An SAE is any experience that suggested a significant hazard, contraindication, side effect, or precaution, and fulfilled any of the following criteria: fatal (resulted in death), life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was medically significant or required intervention to prevent any of the tother outcomes listed here. Safety set was used.
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End point type |
Secondary
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End point timeframe |
From baseline up to Week 88
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No statistical analyses for this end point |
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End point title |
Percentage of Subjects With No Evidence of Cervical HSIL on Histology | ||||||||||||
End point description |
Subjects with no histologic (i.e., biopsies or excisional treatment) evidence of cervical HSIL at Week 36 and subjects in which an excision or biopsy sample was not obtained between the initial dose up to Week 36 were considered to be responders. No evidence of HSIL was defined by histology as negative, squamous atypia, or LSIL. ITT population included all subjects who were randomised.
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||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Week 36
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
VGX-3100 + Electroporation (EP), Placebo + EP | ||||||||||||
Comparison groups |
VGX-3100 + EP v Placebo + EP
|
||||||||||||
Number of subjects included in analysis |
201
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority [4] | ||||||||||||
Method |
|||||||||||||
Parameter type |
Difference in percentage | ||||||||||||
Point estimate |
12.8
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-0.6 | ||||||||||||
upper limit |
24.5 | ||||||||||||
Notes [4] - Superiority was concluded if the lower bound of the 95% CI exceeded 0. |
|
|||||||||||||
End point title |
Percentage of Subjects With No Evidence of HPV-16 and/or HPV-18 in Cervical Samples by Type Specific HPV Testing | ||||||||||||
End point description |
Subjects with no evidence of HPV-16 and/or HPV-18 at the Week 36 time frame and subjects in which an excision or biopsy sample was not obtained between the initial dose up to Week 36 were considered to be responders. Cervical samples for HPV-16 and/or HPV-18 were collected using the ThinPrep®. ITT population included all subjects who were randomised.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Week 36
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
VGX-3100 + Electroporation (EP), Placebo + EP | ||||||||||||
Comparison groups |
VGX-3100 + EP v Placebo + EP
|
||||||||||||
Number of subjects included in analysis |
201
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority [5] | ||||||||||||
Method |
|||||||||||||
Parameter type |
Difference in percentage | ||||||||||||
Point estimate |
18.2
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
5.1 | ||||||||||||
upper limit |
29.4 | ||||||||||||
Notes [5] - Superiority was concluded if the lower bound of the 95% CI exceeded 0. |
|
|||||||||||||
End point title |
Percentage of Subjects With No Evidence of LSIL or HSIL on Histology | ||||||||||||
End point description |
Subjects with no histologic evidence of cervical HSIL, squamous atypia, or LSIL at the Week 36 time frame and subjects in which an excision or biopsy sample was not obtained between the initial dose up to Week 36 were considered to be responders. No evidence of HSIL was defined as no evidence of cervical squamous intraepithelial neoplasia 1 (CIN1), CIN2, or CIN3 on biopsies or excisional treatment. ITT population included all subjects who were randomised.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Week 36
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
VGX-3100 + Electroporation (EP), Placebo + EP | ||||||||||||
Comparison groups |
VGX-3100 + EP v Placebo + EP
|
||||||||||||
Number of subjects included in analysis |
201
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority [6] | ||||||||||||
Method |
|||||||||||||
Parameter type |
Difference in percentage | ||||||||||||
Point estimate |
13.5
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
1.7 | ||||||||||||
upper limit |
23.5 | ||||||||||||
Notes [6] - Superiority was concluded if the lower bound of the 95% CI exceeded 0. |
|
|||||||||||||
End point title |
Percentage of Subjects With No Evidence of LSIL or HSIL and No Evidence of HPV-16 and/or HPV-18 | ||||||||||||
End point description |
Subjects with no histologic evidence of cervical HSIL, squamous atypia, and LSIL, no evidence of HPV-16 and/or HPV-18 by type specific HPV testing at the Week 36 time, and subjects in which an excision or biopsy sample was not obtained between initial dose up to Week 36 were considered to be responders. No evidence of HSIL was defined as no evidence of CIN1, CIN2, or CIN3 on biopsies or excisional treatment. ITT population included all subjects who were randomised.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Week 36
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
VGX-3100 + Electroporation (EP), Placebo + EP | ||||||||||||
Comparison groups |
VGX-3100 + EP v Placebo + EP
|
||||||||||||
Number of subjects included in analysis |
201
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority [7] | ||||||||||||
Method |
|||||||||||||
Parameter type |
Difference in percentage | ||||||||||||
Point estimate |
11.8
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
1.5 | ||||||||||||
upper limit |
20.3 | ||||||||||||
Notes [7] - Superiority was concluded if the lower bound of the 95% CI exceeded 0. |
|
|||||||||||||
End point title |
Percentage of Subjects With No Progression of Cervical HSIL to Cervical Carcinoma | ||||||||||||
End point description |
Subjects with no histologic evidence of cervical Adenocarcinoma in situ or cervical carcinoma at the Week 36 timeframe relative to baseline and subjects in which an excision or biopsy sample was not obtained between initial dose up to Week 36 were considered as responders. ITT population included all subjects who were randomised.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Week 36
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
VGX-3100 + Electroporation (EP), Placebo + EP | ||||||||||||
Comparison groups |
VGX-3100 + EP v Placebo + EP
|
||||||||||||
Number of subjects included in analysis |
201
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority [8] | ||||||||||||
Method |
|||||||||||||
Parameter type |
Difference in percentage | ||||||||||||
Point estimate |
-1.7
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-11.5 | ||||||||||||
upper limit |
10.3 | ||||||||||||
Notes [8] - Superiority was concluded if the lower bound of the 95% CI exceeded 0. |
|
|||||||||||||
End point title |
Percentage of Subjects Who Have Cleared HPV-16 and/or HPV-18 in Non-cervical Anatomic Locations | ||||||||||||
End point description |
Subjects with no evidence of HPV-16 and/or HPV-18 on specimens from noncervical anatomic locations (oropharynx, vagina and intra-anal) at the Week 36 time frame were considered as responder. ITT population included all subjects who were randomised.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Week 36
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
VGX-3100 + Electroporation (EP), Placebo + EP | ||||||||||||
Comparison groups |
VGX-3100 + EP v Placebo + EP
|
||||||||||||
Number of subjects included in analysis |
201
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority [9] | ||||||||||||
Method |
|||||||||||||
Parameter type |
Difference in percentage | ||||||||||||
Point estimate |
10.8
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-0.5 | ||||||||||||
upper limit |
20.1 | ||||||||||||
Notes [9] - Superiority was concluded if the lower bound of the 95% CI exceeded 0. |
|
|||||||||||||||||||||||||
End point title |
Levels of Serum Anti-HPV-16 and Anti-HPV-18 Antibody Concentrations | ||||||||||||||||||||||||
End point description |
A standardized binding enzyme-linked immunosorbent assay (ELISA) was performed to measure the anti–HPV-16/18 antibody response induced by VGX-3100. mITT population included all subjects who received at least one dose of clinical trial treatment and who had the analysis endpoint of interest. Overall number analyzed is the number of subjects with data available for analysis. Number analyzed is the number of subjects with data available for analysis at the specified timepoints.
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
Week 15 and Week 36
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
Statistical analysis title |
Week 15: HPV-16 E7 | ||||||||||||||||||||||||
Comparison groups |
VGX-3100 + EP v Placebo + EP
|
||||||||||||||||||||||||
Number of subjects included in analysis |
189
|
||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
superiority [10] | ||||||||||||||||||||||||
Method |
|||||||||||||||||||||||||
Parameter type |
Difference in median | ||||||||||||||||||||||||
Point estimate |
224
|
||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||
lower limit |
24 | ||||||||||||||||||||||||
upper limit |
224 | ||||||||||||||||||||||||
Notes [10] - Superiority was concluded if the lower bound of the 95% CI exceeded 0. |
|||||||||||||||||||||||||
Statistical analysis title |
Week 36: HPV-16 E7 | ||||||||||||||||||||||||
Comparison groups |
VGX-3100 + EP v Placebo + EP
|
||||||||||||||||||||||||
Number of subjects included in analysis |
189
|
||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
superiority [11] | ||||||||||||||||||||||||
Method |
|||||||||||||||||||||||||
Parameter type |
Difference in median | ||||||||||||||||||||||||
Point estimate |
0
|
||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||
lower limit |
0 | ||||||||||||||||||||||||
upper limit |
0 | ||||||||||||||||||||||||
Notes [11] - Superiority was concluded if the lower bound of the 95% CI exceeded 0. |
|||||||||||||||||||||||||
Statistical analysis title |
Week 15: HPV-18 E7 | ||||||||||||||||||||||||
Comparison groups |
VGX-3100 + EP v Placebo + EP
|
||||||||||||||||||||||||
Number of subjects included in analysis |
189
|
||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
superiority [12] | ||||||||||||||||||||||||
Method |
|||||||||||||||||||||||||
Parameter type |
Difference in median | ||||||||||||||||||||||||
Point estimate |
2024
|
||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||
lower limit |
2000 | ||||||||||||||||||||||||
upper limit |
6050 | ||||||||||||||||||||||||
Notes [12] - Superiority was concluded if the lower bound of the 95% CI exceeded 0. |
|||||||||||||||||||||||||
Statistical analysis title |
Week 36: HPV-18 E7 | ||||||||||||||||||||||||
Comparison groups |
VGX-3100 + EP v Placebo + EP
|
||||||||||||||||||||||||
Number of subjects included in analysis |
189
|
||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
superiority [13] | ||||||||||||||||||||||||
Method |
|||||||||||||||||||||||||
Parameter type |
Difference in median | ||||||||||||||||||||||||
Point estimate |
224
|
||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||
lower limit |
74 | ||||||||||||||||||||||||
upper limit |
674 | ||||||||||||||||||||||||
Notes [13] - Superiority was concluded if the lower bound of the 95% CI exceeded 0. |
|
|||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Change From Baseline in Interferon-Gamma Response Magnitude | ||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Assessment of cellular immune activity occurred via the application of the Interferon-γ enzyme-linked immunosorbent spot (IFN-γ ELISpot). Peripheral blood mononuclear cells (PBMCs) isolated from whole blood sample were used for analysis. mITT population included all subjects who received at least one dose of clinical trial treatment and who had the analysis endpoint of interest. Overall number analysed is the number of subjects with data available for analysis. Number analysed is the number of subjects with data available for analysis at the specified timepoints.
|
||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Baseline; Week 15 and Week 36
|
||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||
Statistical analysis title |
HPV-16 E6: Week 15 | ||||||||||||||||||||||||||||||||||||||||||||||||
Comparison groups |
VGX-3100 + EP v Placebo + EP
|
||||||||||||||||||||||||||||||||||||||||||||||||
Number of subjects included in analysis |
170
|
||||||||||||||||||||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||||||||||||||||||||||
Analysis type |
superiority [14] | ||||||||||||||||||||||||||||||||||||||||||||||||
Method |
|||||||||||||||||||||||||||||||||||||||||||||||||
Parameter type |
Difference in median | ||||||||||||||||||||||||||||||||||||||||||||||||
Point estimate |
13.33
|
||||||||||||||||||||||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||||||||||||||||||||||||||
lower limit |
8.33 | ||||||||||||||||||||||||||||||||||||||||||||||||
upper limit |
20 | ||||||||||||||||||||||||||||||||||||||||||||||||
Notes [14] - Superiority was concluded if the lower bound of the 95% CI exceeded 0. |
|||||||||||||||||||||||||||||||||||||||||||||||||
Statistical analysis title |
HPV-16 E6: Week 36 | ||||||||||||||||||||||||||||||||||||||||||||||||
Comparison groups |
VGX-3100 + EP v Placebo + EP
|
||||||||||||||||||||||||||||||||||||||||||||||||
Number of subjects included in analysis |
170
|
||||||||||||||||||||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||||||||||||||||||||||
Analysis type |
superiority [15] | ||||||||||||||||||||||||||||||||||||||||||||||||
Method |
|||||||||||||||||||||||||||||||||||||||||||||||||
Parameter type |
Difference in median | ||||||||||||||||||||||||||||||||||||||||||||||||
Point estimate |
8.33
|
||||||||||||||||||||||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||||||||||||||||||||||||||
lower limit |
3.33 | ||||||||||||||||||||||||||||||||||||||||||||||||
upper limit |
11.67 | ||||||||||||||||||||||||||||||||||||||||||||||||
Notes [15] - Superiority was concluded if the lower bound of the 95% CI exceeded 0. |
|||||||||||||||||||||||||||||||||||||||||||||||||
Statistical analysis title |
HPV-16 E7: Week 15 | ||||||||||||||||||||||||||||||||||||||||||||||||
Comparison groups |
VGX-3100 + EP v Placebo + EP
|
||||||||||||||||||||||||||||||||||||||||||||||||
Number of subjects included in analysis |
170
|
||||||||||||||||||||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||||||||||||||||||||||
Analysis type |
superiority [16] | ||||||||||||||||||||||||||||||||||||||||||||||||
Method |
|||||||||||||||||||||||||||||||||||||||||||||||||
Parameter type |
Difference in median | ||||||||||||||||||||||||||||||||||||||||||||||||
Point estimate |
10.83
|
||||||||||||||||||||||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||||||||||||||||||||||||||
lower limit |
5 | ||||||||||||||||||||||||||||||||||||||||||||||||
upper limit |
15 | ||||||||||||||||||||||||||||||||||||||||||||||||
Notes [16] - Superiority was concluded if the lower bound of the 95% CI exceeded 0. |
|||||||||||||||||||||||||||||||||||||||||||||||||
Statistical analysis title |
HPV-16 E7: Week 36 | ||||||||||||||||||||||||||||||||||||||||||||||||
Comparison groups |
VGX-3100 + EP v Placebo + EP
|
||||||||||||||||||||||||||||||||||||||||||||||||
Number of subjects included in analysis |
170
|
||||||||||||||||||||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||||||||||||||||||||||
Analysis type |
superiority [17] | ||||||||||||||||||||||||||||||||||||||||||||||||
Method |
|||||||||||||||||||||||||||||||||||||||||||||||||
Parameter type |
Difference in median | ||||||||||||||||||||||||||||||||||||||||||||||||
Point estimate |
7.5
|
||||||||||||||||||||||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||||||||||||||||||||||||||
lower limit |
1.67 | ||||||||||||||||||||||||||||||||||||||||||||||||
upper limit |
10 | ||||||||||||||||||||||||||||||||||||||||||||||||
Notes [17] - Superiority was concluded if the lower bound of the 95% CI exceeded 0. |
|||||||||||||||||||||||||||||||||||||||||||||||||
Statistical analysis title |
HPV-18 E6: Week 15 | ||||||||||||||||||||||||||||||||||||||||||||||||
Comparison groups |
VGX-3100 + EP v Placebo + EP
|
||||||||||||||||||||||||||||||||||||||||||||||||
Number of subjects included in analysis |
170
|
||||||||||||||||||||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||||||||||||||||||||||
Analysis type |
superiority [18] | ||||||||||||||||||||||||||||||||||||||||||||||||
Method |
|||||||||||||||||||||||||||||||||||||||||||||||||
Parameter type |
Difference in median | ||||||||||||||||||||||||||||||||||||||||||||||||
Point estimate |
50.83
|
||||||||||||||||||||||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||||||||||||||||||||||||||
lower limit |
31.67 | ||||||||||||||||||||||||||||||||||||||||||||||||
upper limit |
66.67 | ||||||||||||||||||||||||||||||||||||||||||||||||
Notes [18] - Superiority was concluded if the lower bound of the 95% CI exceeded 0. |
|||||||||||||||||||||||||||||||||||||||||||||||||
Statistical analysis title |
HPV-18 E6: Week 36 | ||||||||||||||||||||||||||||||||||||||||||||||||
Comparison groups |
VGX-3100 + EP v Placebo + EP
|
||||||||||||||||||||||||||||||||||||||||||||||||
Number of subjects included in analysis |
170
|
||||||||||||||||||||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||||||||||||||||||||||
Analysis type |
superiority [19] | ||||||||||||||||||||||||||||||||||||||||||||||||
Method |
|||||||||||||||||||||||||||||||||||||||||||||||||
Parameter type |
Difference in median | ||||||||||||||||||||||||||||||||||||||||||||||||
Point estimate |
38.33
|
||||||||||||||||||||||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||||||||||||||||||||||||||
lower limit |
18.33 | ||||||||||||||||||||||||||||||||||||||||||||||||
upper limit |
51.67 | ||||||||||||||||||||||||||||||||||||||||||||||||
Notes [19] - Superiority was concluded if the lower bound of the 95% CI exceeded 0. |
|||||||||||||||||||||||||||||||||||||||||||||||||
Statistical analysis title |
HPV-18 E7: Week 15 | ||||||||||||||||||||||||||||||||||||||||||||||||
Comparison groups |
VGX-3100 + EP v Placebo + EP
|
||||||||||||||||||||||||||||||||||||||||||||||||
Number of subjects included in analysis |
170
|
||||||||||||||||||||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||||||||||||||||||||||
Analysis type |
superiority [20] | ||||||||||||||||||||||||||||||||||||||||||||||||
Method |
|||||||||||||||||||||||||||||||||||||||||||||||||
Parameter type |
Difference in median | ||||||||||||||||||||||||||||||||||||||||||||||||
Point estimate |
14.17
|
||||||||||||||||||||||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||||||||||||||||||||||||||
lower limit |
6.67 | ||||||||||||||||||||||||||||||||||||||||||||||||
upper limit |
18.33 | ||||||||||||||||||||||||||||||||||||||||||||||||
Notes [20] - Superiority was concluded if the lower bound of the 95% CI exceeded 0. |
|||||||||||||||||||||||||||||||||||||||||||||||||
Statistical analysis title |
HPV-18 E7: Week 36 | ||||||||||||||||||||||||||||||||||||||||||||||||
Comparison groups |
VGX-3100 + EP v Placebo + EP
|
||||||||||||||||||||||||||||||||||||||||||||||||
Number of subjects included in analysis |
170
|
||||||||||||||||||||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||||||||||||||||||||||
Analysis type |
superiority [21] | ||||||||||||||||||||||||||||||||||||||||||||||||
Method |
|||||||||||||||||||||||||||||||||||||||||||||||||
Parameter type |
Difference in median | ||||||||||||||||||||||||||||||||||||||||||||||||
Point estimate |
10
|
||||||||||||||||||||||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||||||||||||||||||||||||||
lower limit |
5 | ||||||||||||||||||||||||||||||||||||||||||||||||
upper limit |
15 | ||||||||||||||||||||||||||||||||||||||||||||||||
Notes [21] - Superiority was concluded if the lower bound of the 95% CI exceeded 0. |
|
|||||||||||||||||||||||||||||||
End point title |
Change From Baseline (CFB) in Flow Cytometry Response Magnitude | ||||||||||||||||||||||||||||||
End point description |
Assessment of cellular immune activity was measured using the application flow cytometry for the purposes of performing a Lytic Granule Loading Assay. The Lytic Granule Loading assay examines the following external cellular markers: CD3, CD4, CD8 (T cell identification), CD137, CD38 and CD69 (T cell activation markers) as well as PD-1 (exhaustion/activation marker). Here change from baseline in CD8+CD137+Perforin+, CD8+CD38+Perforin+ and CD8+CD69+Perforin+ are reported. mITT population included all subjects who received at least one dose of clinical trial treatment and who had the analysis endpoint of interest. Overall number analysed is the number of subjects with data available for analysis. Number analysed is the number of subjects with data available for analysis at the specified timepoints.
|
||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||
End point timeframe |
Baseline, Week 15
|
||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||
Statistical analysis title |
Parameter: CD8+CD137+Perforin+ | ||||||||||||||||||||||||||||||
Comparison groups |
VGX-3100 + EP v Placebo + EP
|
||||||||||||||||||||||||||||||
Number of subjects included in analysis |
172
|
||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||||
Analysis type |
superiority [22] | ||||||||||||||||||||||||||||||
Method |
|||||||||||||||||||||||||||||||
Parameter type |
Difference in median | ||||||||||||||||||||||||||||||
Point estimate |
0.035
|
||||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||||||||
lower limit |
0.002 | ||||||||||||||||||||||||||||||
upper limit |
0.046 | ||||||||||||||||||||||||||||||
Notes [22] - Superiority was concluded if the lower bound of the 95% CI exceeded 0. |
|||||||||||||||||||||||||||||||
Statistical analysis title |
Parameter: CD8+CD38+Perforin+ | ||||||||||||||||||||||||||||||
Comparison groups |
VGX-3100 + EP v Placebo + EP
|
||||||||||||||||||||||||||||||
Number of subjects included in analysis |
172
|
||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||||
Analysis type |
superiority [23] | ||||||||||||||||||||||||||||||
Method |
|||||||||||||||||||||||||||||||
Parameter type |
Difference in median | ||||||||||||||||||||||||||||||
Point estimate |
0.011
|
||||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||||||||
lower limit |
0 | ||||||||||||||||||||||||||||||
upper limit |
0.014 | ||||||||||||||||||||||||||||||
Notes [23] - Superiority was concluded if the lower bound of the 95% CI exceeded 0. |
|||||||||||||||||||||||||||||||
Statistical analysis title |
Parameter: CD8+CD69+Perforin+ | ||||||||||||||||||||||||||||||
Comparison groups |
VGX-3100 + EP v Placebo + EP
|
||||||||||||||||||||||||||||||
Number of subjects included in analysis |
172
|
||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||||
Analysis type |
superiority [24] | ||||||||||||||||||||||||||||||
Method |
|||||||||||||||||||||||||||||||
Parameter type |
Difference in median | ||||||||||||||||||||||||||||||
Point estimate |
0.044
|
||||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||||||||
lower limit |
0.017 | ||||||||||||||||||||||||||||||
upper limit |
0.058 | ||||||||||||||||||||||||||||||
Notes [24] - Superiority was concluded if the lower bound of the 95% CI exceeded 0. |
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse events information
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
From baseline up to Week 88
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse event reporting additional description |
Safety set included all subjects who received at least one dose of clinical trial treatment. One subject received mixed treatment and was excluded from the safety analysis.
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
24.0
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting groups
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
VGX-3100 + EP
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Subjects received three IM injections of 6 mg (in 1 mL) VGX-3100 followed by EP using the CELLECTRA™-5PSP device on Day 0, Week 4, and Week 12. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo + EP
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Subjects received three IM injections of 1 mL VGX-3100 matching placebo followed by EP using the CELLECTRA™-5PSP device on Day 0, Week 4, and Week 12. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
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Frequency threshold for reporting non-serious adverse events: 5% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||
Substantial protocol amendments (globally) |
|||
Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
06 Jun 2016 |
The main changes in Protocol version 2.0 include the following:
• Added rationale for selection of nonfrozen formulation for Phase 3 clinical trial.
• Added additional background information to Section 2 Study Design.
• Clarified inclusion and exclusion criteria.
• Administrative changes made throughout the protocol for clarification, that did not significantly affect the safety of subjects, clinical trial scope, or scientific quality of the protocol.
|
||
10 Jun 2016 |
The main changes in Protocol version 2.1 include the following:
• Administrative and formatting changes were made to protocol version 2.0 dated 06Jun2016 resulting in protocol version 2.1 dated 10Jun2016. |
||
23 Sep 2016 |
The main changes in Protocol version 3.0 include the following:
• Name of the investigational product (IP) was changed from VGX-3100X to VGX-3100. The term VGX-3100 as used in protocol version 3.0 denoted 3.0 ± 0.2 mg/mL pGX3001 bulk plasmid and 3.0 ± 0.2 mg/mL pGX3002 bulk plasmid in SSC buffer, refrigerated formulation.
• The population for the primary analysis for the clinical trial was changed from mITT based on complete data to intent-to-treat (ITT) analysis. Based on this change, the number of subjects to be enrolled in the clinical trial was now 198 instead of 165.
• Modifications in objectives and endpoints
• Modifications in inclusion and exclusion criteria
• Modifications to the clinical trial evaluations
• Section 2.1.3 Definition of Responder and Nonresponde
• Added information on supplementation of subjects in case more than 10% of subjects randomly assigned to clinical trial treatment discontinued prior to the Week 36 primary endpoint procedure.
• Section 5.7 Return and Destruction of Investigational Product
• Section 6.1.1 Screening Evaluations
• Section 6.15.1 Prohibited Concomitant Medications and Treatments
• Added that progression of HSIL to microinvasive or invasive squamous cell carcinoma should be reported as an SAE.
• Section 7.3.1 was modified to replace the term “events requiring expedited reporting” to “adverse events of special interest (AESI)”. Added clarification on reporting requirements to sponsor.
• Section 7.4.2 was updated to reflect change in reporting contact details in event of SAE.
• Section 8 Statistical Analysis section
• Section 9.4.2 Pathology Adjudication Committee
• Additional administrative clarifications were made to the protocol that did not significantly affect the safety of subjects, clinical trial scope, or scientific quality of the protocol. |
||
29 Mar 2018 |
The main changes in Protocol version 4.0 include the following:
• Modifications and updates to the hypothesis, objectives, and endpoints
• Revisions to the inclusion and exclusion criteria
• Updates were made to the Schedule of Events table to align with the protocol text and above-mentioned changes to the clinical trial endpoints and inclusion and exclusion criteria.
• General updates and clarifications
• Section 7.3 (Safety and Toxicity Management) was modified to align with safety assessments as stated in the section describing clinical trial design of clinical protocol synopsis.
• Section 8 (Statistical Analysis Plan) was revised to align with the changes made to objectives and endpoints.
• Section 9.4.2 (Pathology Adjudication Committee) was modified to refer to the PAC charter, which had the most current information regarding the PAC review process.
• The PDC was unchanged but was removed from the Appendix since the PDC was a separate document.
• Additional minor grammatical and administrative changes were made throughout the document for improving the general readability of the protocol.
|
||
20 Nov 2019 |
The main changes in Protocol version 5.0 include the following:
• Human leukocyte antigen (HLA) testing and associated exploratory endpoint 2 was removed from the protocol in consideration of the HPV-003 clinical trial results which showed no clear association of HLA background as a predictor of response.
• Group-level unblinded (VGX-3100, placebo) summaries and analyses of efficacy were to be produced once the primary endpoint Week 36 visit data were collected for all subjects.
• The stopping rules outlined in Section 7.3.2, Stopping Rules (Criteria for Pausing of Study), were clarified to focus on unexpected, verified events and not include events that were already described as known adverse drug reactions.
• Additional administrative clarifications were made to the protocol that did not significantly affect the safety of subjects, clinical trial scope, or scientific quality of the protocol. |
||
Interruptions (globally) |
|||
Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |