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NCT03721978

REVEAL 2 Trial (Evaluation of VGX-3100 and Electroporation for the Treatment of Cervical HSIL)

Completed Phase 3 Results posted Last updated 17 October 2024
What this trial tests

Phase 3 trial testing VGX-3100 in Cervical Dysplasia in 203 participants. Completed in 15 September 2022.

Timeline
28 February 2019
Primary endpoint
23 August 2022
15 September 2022

Quick facts

Lead sponsorInovio Pharmaceuticals
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingquadruple
Primary purposetreatment
Enrollment203
Start date28 February 2019
Primary completion23 August 2022
Estimated completion15 September 2022
Sites53 locations across South Africa, Finland, Estonia, Poland, Argentina, Puerto Rico, Lithuania, Spain

Drugs / interventions tested

Conditions studied

Sponsor

Inovio Pharmaceuticals — full company profile →

Who can join

18 and older, female only, with Cervical Dysplasia or Cervical High Grade Squamous Intraepithelial Lesion. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Baseline Biomarker-positive Participants for ITT Population: Percentage of Participants With No Histologic Evidence of Cervical HSIL on Histology Sample and No Evidence of HPV-16 and/or HPV-18 in Cervical Samples Primary · At Week 36

Baseline biomarker-positive participants with no histologic (i.e., biopsies or excisional treatment) evidence of cervical HSIL, no evidence of HPV-16 and/or HPV-18 at Week 36, and participants who did not have unscheduled excision or biopsy sample 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™. The efficacy time frame is defined by a biopsy or surgical excision at an

GroupValue95% CI
VGX-3100 + EP28.6
Matched Placebo + EP0
Baseline Biomarker-positive Participants for Safety Population: Number of Participants With Any Local and Systemic Adverse Events (AEs) Secondary · From Baseline to Week 40

An AE is any untoward medical occurrence in a participant 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 the pharmaceutical product, whether or not considered related to the pharmaceutical product. Pre-existing conditions which worsen during a study are also considered as AEs. Nausea, fatigue, injection site bruising, injection site erythema, injection site haematoma, injection site induration, injection site

Nausea
GroupValue95% CI
VGX-3100 + EP6
Matched Placebo + EP0
Fatigue
GroupValue95% CI
VGX-3100 + EP10
Matched Placebo + EP2
Injection Site Bruising
GroupValue95% CI
VGX-3100 + EP7
Matched Placebo + EP1
Injection Site Erythema
GroupValue95% CI
VGX-3100 + EP4
Matched Placebo + EP2
Injection Site Haematoma
GroupValue95% CI
VGX-3100 + EP1
Matched Placebo + EP0
Injection Site Induration
GroupValue95% CI
VGX-3100 + EP1
Matched Placebo + EP0
Injection Site Pain
GroupValue95% CI
VGX-3100 + EP19
Matched Placebo + EP4
Injection Site Pruritus
GroupValue95% CI
VGX-3100 + EP7
Matched Placebo + EP2
Safety Population: Number of Participants With Local and Systemic AEs Secondary · From Baseline to Week 40

An AE is any untoward medical occurrence in a participant 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 the pharmaceutical product, whether or not considered related to the pharmaceutical product. Pre-existing conditions which worsen during a study are also considered as AEs. Nausea, chills, fatigue, injection site bruising, injection site erythema, injection site haematoma, injection site haemorrhage, inject

Nausea
GroupValue95% CI
VGX-3100 + EP36
Matched Placebo + EP17
Mixed Treatment0
Chills
GroupValue95% CI
VGX-3100 + EP2
Matched Placebo + EP1
Mixed Treatment0
Fatigue
GroupValue95% CI
VGX-3100 + EP56
Matched Placebo + EP33
Mixed Treatment1
Injection Site Bruising
GroupValue95% CI
VGX-3100 + EP21
Matched Placebo + EP11
Mixed Treatment0
Injection Site Erythema
GroupValue95% CI
VGX-3100 + EP36
Matched Placebo + EP15
Mixed Treatment0
Injection Site Haematoma
GroupValue95% CI
VGX-3100 + EP10
Matched Placebo + EP7
Mixed Treatment0
Injection Site Haemorrhage
GroupValue95% CI
VGX-3100 + EP1
Matched Placebo + EP0
Mixed Treatment0
Injection Site Induration
GroupValue95% CI
VGX-3100 + EP3
Matched Placebo + EP0
Mixed Treatment0
Baseline Biomarker-positive Participants for Safety Population: Number of Participants With Any Treatment Emergent AEs (TEAEs) and Serious TEAEs (Including Suspected Unexpected Serious Adverse Reaction [SUSAR] and Unexpected Adverse Device Effect [UADE]) Secondary · From Baseline to Week 40

AE is any untoward medical occurrence in a participant administered a pharmaceutical product, which does not necessarily have a causal relationship with the treatment. Serious AE (SAE) is any experience that suggested significant hazard, contraindication, side effect/precaution, \& fulfilled any of the following: fatal, life-threatening, required in-patient hospitalization/prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was medically significant/required intervention to prevent other outcomes. TEAEs a

Participants with any TEAEs
GroupValue95% CI
VGX-3100 + EP20
Matched Placebo + EP4
Participants with any Serious TEAEs
GroupValue95% CI
VGX-3100 + EP3
Matched Placebo + EP0
Participants with SUSAR
GroupValue95% CI
VGX-3100 + EP0
Matched Placebo + EP0
Participants with UADE
GroupValue95% CI
VGX-3100 + EP0
Matched Placebo + EP0
Safety Population: Number of Participants With Any TEAEs and Serious TEAEs (Including SUSAR and UADE) Secondary · From Baseline to Week 40

AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have a causal relationship with the treatment. SAE is any experience that suggested significant hazard, contraindication, side effect, or precaution, and fulfilled any of the following criteria: fatal, 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 other outcome

Participants with any TEAEs
GroupValue95% CI
VGX-3100 + EP131
Matched Placebo + EP67
Mixed Treatment1
Participants with any Serious TEAEs
GroupValue95% CI
VGX-3100 + EP9
Matched Placebo + EP9
Mixed Treatment0
Participants with SUSAR
GroupValue95% CI
VGX-3100 + EP0
Matched Placebo + EP0
Mixed Treatment0
Participants with UADE
GroupValue95% CI
VGX-3100 + EP0
Matched Placebo + EP0
Mixed Treatment0
ITT Population: Percentage of Participants With No Histologic Evidence of Cervical HSIL on Histology Sample and No Evidence of HPV-16 and/or HPV-18 in Cervical Samples Secondary · At Week 36

Participants with no histologic (i.e., biopsies or excisional treatment) evidence of cervical HSIL, no evidence of HPV-16 and/or HPV-18 at Week 36, and participants who did not have unscheduled excision or biopsy sample 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™. The efficacy time frame is defined by a biopsy or surgical excision at any time starting from 14 days

GroupValue95% CI
VGX-3100 + EP27.6
Matched Placebo + EP8.7
Baseline Biomarker-positive Participants for ITT Population: Percentage of Participants With No Histologic Evidence of Cervical HSIL on Histology Sample Secondary · At Week 36

Baseline biomarker-positive participants with no histologic (i.e., biopsies or excisional treatment) evidence of cervical HSIL at Week 36 and participants who did not have unscheduled excision or biopsy sample 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. The efficacy time frame is defined by a biopsy or surgical excision at any time starting from 14 days prior to the protocol-specified target date of Week 36. The first tissue removal sample within the time frame determines t

GroupValue95% CI
VGX-3100 + EP38.1
Matched Placebo + EP25.0
ITT Population: Percentage of Participants With No Histologic Evidence of Cervical HSIL on Histology Sample Secondary · At Week 36

Participants with no histologic (i.e., biopsies or excisional treatment) evidence of cervical HSIL at Week 36 and participants who did not have unscheduled excision or biopsy sample 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. The efficacy time frame is defined by a biopsy or surgical excision at any time starting from 14 days prior to the protocol-specified target date of Week 36. The first tissue removal sample within the time frame determines the histology endpoint.

GroupValue95% CI
VGX-3100 + EP34.3
Matched Placebo + EP21.7
Baseline Biomarker-positive Participants for ITT Population: Percentage of Participants With No Evidence of HPV-16 and/or HPV-18 in Cervical Samples by Type Specific HPV Testing Secondary · At Week 36

Baseline biomarker-positive participants with no evidence of HPV-16 and/or HPV-18 at Week 36 time frame and participants in whom 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™. The efficacy time frame is defined by a biopsy or surgical excision at any time starting from 14 days prior to the protocol-specified target date of Week 36. The first tissue removal sample within the time frame determines the histology endpoint.

GroupValue95% CI
VGX-3100 + EP38.1
Matched Placebo + EP0
ITT Population: Percentage of Participants With No Evidence of HPV-16 and/or HPV-18 in Cervical Samples by Type Specific HPV Testing Secondary · At Week 36

Participants with no evidence of HPV-16 and/or HPV-18 at Week 36 and participants who did not have unscheduled excision or biopsy sample 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™. The efficacy time frame is defined by a biopsy or surgical excision at any time starting from 14 days prior to the protocol-specified target date of Week 36. The first tissue removal sample within the time frame determines the histology endpoint.

GroupValue95% CI
VGX-3100 + EP38.1
Matched Placebo + EP10.1
Baseline Biomarker-positive Participants for ITT Population: Percentage of Participants With No Histologic Evidence of LSIL or HSIL on Histology Sample Secondary · At Week 36

Baseline biomarker-positive participants with no histologic evidence of cervical HSIL, squamous atypia, or LSIL at Week 36 and participants who did not have unscheduled excision or biopsy sample obtained between the initial dose up to Week 36 were considered to be responders. No evidence of LSIL was defined as no evidence of cervical squamous intraepithelial neoplasia 1 (CIN1), CIN2, or CIN3 on biopsies or excisional treatment. No evidence of HSIL was defined by histology as negative, squamous atypia, or LSIL. The efficacy time frame is defined by a biopsy or surgical excision at any time star

GroupValue95% CI
VGX-3100 + EP38.1
Matched Placebo + EP25.0
ITT Population: Percentage of Participants With No Evidence of Histologic LSIL or HSIL on Histology Sample Secondary · At Week 36

Participants with no histologic evidence of cervical HSIL, squamous atypia, or LSIL at Week 36 and participants who did not have unscheduled excision or biopsy sample obtained between the initial dose up to Week 36 were considered to be responders. No evidence of LSIL was defined as no evidence of CIN1, CIN2, or CIN3 on biopsies or excisional treatment. No evidence of HSIL was defined by histology as negative, squamous atypia, or LSIL. The efficacy time frame is defined by a biopsy or surgical excision at any time starting from 14 days prior to the protocol-specified target date of Week 36. Th

GroupValue95% CI
VGX-3100 + EP32.1
Matched Placebo + EP14.5

Adverse events — posted to ClinicalTrials.gov

Time frame: From Baseline to Week 40. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

VGX-3100 + EP
Serious: 9/134 (7%)
Deaths: 0/134
Matched Placebo + EP
Serious: 9/67 (13%)
Deaths: 0/67
Mixed Treatment
Serious: 0/1 (0%)
Deaths: 0/1

Serious adverse events (7 terms)

ReactionSystemVGX-3100 + EPMatched Placebo + EPMixed Treatment
Cervix carcinoma stage 0Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous cell carcinomaNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous cell carcinoma of the cervixNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma of the cervixNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Ovarian ruptureReproductive system and breast disorders
AppendicitisInfections and infestations
COVID-19Infections and infestations
Other adverse events (18 terms — click to expand)

ReactionSystemVGX-3100 + EPMatched Placebo + EPMixed Treatment
Injection site painGeneral disorders
HeadacheNervous system disorders
FatigueGeneral disorders
MyalgiaMusculoskeletal and connective tissue disorders
Injection site swellingGeneral disorders
Injection site erythemaGeneral disorders
NauseaGastrointestinal disorders
Injection site pruritusGeneral disorders
ArthralgiaMusculoskeletal and connective tissue disorders
Injection site bruisingGeneral disorders
MalaiseGeneral disorders
COVID-19Infections and infestations
PyrexiaGeneral disorders
Injection site haematomaGeneral disorders
DizzinessNervous system disorders
Urinary tract infectionInfections and infestations
DysmenorrhoeaReproductive system and breast disorders
Back painMusculoskeletal and connective tissue disorders

Most-reported serious reactions: Cervix carcinoma stage 0, Squamous cell carcinoma, Squamous cell carcinoma of the cervix, Adenocarcinoma of the cervix, Ovarian rupture, Appendicitis, COVID-19.

Data from ClinicalTrials.gov NCT03721978 adverse events section.

Sponsor's own description

HPV-303 is a prospective, randomized, double-blind, placebo-controlled study of VGX-3100 delivered intramuscularly (IM) followed by electroporation (EP) delivered with CELLECTRA™ 5PSP in adult women with histologically confirmed high-grade squamous intraepithelial lesions (HSIL) (cervical intraepithelial neoplasia grade 2 \[CIN2\] or grade 3 \[CIN3\]) of the cervix, associated with human papillomavirus (HPV-16) and/or HPV-18.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Cancer vaccines as promising immuno-therapeutics: platforms and current progress.
    Liu J, Fu M, Wang M, Wan D, et al · · 2022 · cited 497× · PMID 35303904 · DOI 10.1186/s13045-022-01247-x
  2. Cancer DNA vaccines: current preclinical and clinical developments and future perspectives.
    Lopes A, Vandermeulen G, Préat V. · · 2019 · cited 277× · PMID 30953535 · DOI 10.1186/s13046-019-1154-7
  3. Cervical Cancer Immunotherapy: Facts and Hopes.
    Ferrall L, Lin KY, Roden RBS, Hung CF, et al · · 2021 · cited 255× · PMID 33888488 · DOI 10.1158/1078-0432.ccr-20-2833
  4. Vaccine Therapies for Cancer: Then and Now.
    Morse MA, Gwin WR, Mitchell DA. · · 2021 · cited 156× · PMID 33512679 · DOI 10.1007/s11523-020-00788-w
  5. Comparison of DNA and mRNA vaccines against cancer.
    Jahanafrooz Z, Baradaran B, Mosafer J, Hashemzaei M, et al · · 2020 · cited 134× · PMID 31843577 · DOI 10.1016/j.drudis.2019.12.003
  6. Therapeutic Vaccines for HPV-Associated Malignancies.
    Smalley Rumfield C, Roller N, Pellom ST, Schlom J, et al · · 2020 · cited 87× · PMID 33117742 · DOI 10.2147/itt.s273327
  7. Recent Advances and Challenges in Cancer Immunotherapy.
    Peterson C, Denlinger N, Yang Y. · · 2022 · cited 74× · PMID 36010965 · DOI 10.3390/cancers14163972
  8. Immunomodulation to enhance the efficacy of an HPV therapeutic vaccine.
    Smalley Rumfield C, Pellom ST, Morillon Ii YM, Schlom J, et al · · 2020 · cited 61× · PMID 32554612 · DOI 10.1136/jitc-2020-000612

Verify or expand the search:

Other trials of VGX-3100

Trials testing the same drug.

Other recruiting trials for Cervical Dysplasia

Currently open trials in the same condition.

Other Inovio Pharmaceuticals trials

Trials by the same sponsor.

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Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT03721978.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing