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REVEAL 1 (Evaluation of VGX-3100 and Electroporation for the Treatment of Cervical HSIL) (REVEAL 1)

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ClinicalTrials.gov Identifier: NCT03185013
Recruitment Status : Recruiting
First Posted : June 14, 2017
Last Update Posted : November 22, 2018
Sponsor:
Information provided by (Responsible Party):
Inovio Pharmaceuticals

Brief Summary:
HPV-301 is a prospective, randomized, double-blind, placebo controlled Phase 3 study to determine the efficacy, safety, and tolerability of VGX-3100 administered by intramuscular (IM) injection followed by electroporation (EP) delivered with CELLECTRA™ 5PSP in adult women with histologically confirmed cervical high grade squamous intraepithelial lesion (HSIL) (cervical intraepithelial neoplasia grade 2 [CIN2] or grade 3 [CIN3]) associated with human papillomavirus (HPV) 16 and/or HPV-18.

Condition or disease Intervention/treatment Phase
Cervical Dysplasia Cervical High Grade Squamous Intraepithelial Lesion HSIL Biological: VGX-3100 Biological: Placebo Device: Electroporation (EP) Phase 3

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 198 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : June 13, 2017
Estimated Primary Completion Date : August 2019
Estimated Study Completion Date : August 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: VGX-3100 + EP
IM injections with VGX-3100 followed by electroporation (EP) using the CELLECTRA™-5PSP device on Day 0, Week 4 and Week 12.
Biological: VGX-3100
1 milliLiter (mL) VGX-3100 will be injected IM and delivered by EP using CELLECTRA™-5PSP on Day 0, Week 4 and Week 12.

Device: Electroporation (EP)
Intramuscular injection followed by EP with the CELLECTRA™ 5PSP device.

Placebo Comparator: Placebo + EP
IM injections with matching placebo followed by EP using the CELLECTRA™-5PSP device on Day 0, Week 4 and Week 12.
Biological: Placebo
1 mL of Placebo will be injected IM and delivered by EP using CELLECTRA™-5PSP on Day 0, Week 4 and Week 12.

Device: Electroporation (EP)
Intramuscular injection followed by EP with the CELLECTRA™ 5PSP device.




Primary Outcome Measures :
  1. Percentage of Participants with No Evidence of Cervical HSIL on Histology and No Evidence of HPV-16 and/or HPV-18 in Cervical Samples at Week 36 [ Time Frame: At Week 36 ]
    Participants will be evaluated for evidence of cervical HSIL on histology as well as evidence of HPV-16 and/or HPV-18 in cervical samples by type-specific HPV testing at the Week 36 visit.


Secondary Outcome Measures :
  1. Safety: Number of Participants with Any Adverse Events (AEs) and Serious Adverse Events (SAEs) Following Investigational Treatment and for the Duration of the Study [ Time Frame: From baseline to Week 88 ]
    An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event 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 adverse events. 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 other outcomes listed here.

  2. Percentage of Participants with No Evidence of Cervical HSIL at Week 36 [ Time Frame: At Week 36 ]
    Participants will be evaluated for evidence of cervical HSIL on histology at the Week 36 visit.

  3. Percentage of Participants with No Evidence of HPV-16 and/or HPV-18 in Cervical Samples at Week 36 [ Time Frame: At Week 36 ]
    Participants will be evaluated for evidence of HPV-16 and/or HPV-18 in cervical samples by type-specific HPV testing.

  4. Percentage of Participants with No Evidence of Low Grade Squamous Intraepithelial Lesion (LSIL) or HSIL at Week 36 [ Time Frame: At Week 36 ]
    Participants will be evaluated for evidence of LSIL (i.e. slightly abnormal cells on the surface of the cervix) or HSIL (i.e. evidence of cervical intraepithelial neoplasia grade 1 [CIN1], CIN2 or CIN3 on biopsies or excisional treatment) on histology at the Week 36 visit.

  5. Percentage of Participants with No Evidence of LSIL or HSIL and No Evidence of HPV-16 and/or HPV-18 at Week 36 [ Time Frame: At Week 36 ]
    Participants will be evaluated for evidence of LSIL (i.e. slightly abnormal cells on the surface of the cervix) or HSIL (i.e. evidence of CIN1, CIN2 or CIN3 on biopsies or excisional treatment) on histology and no evidence of HPV-16 and/or HPV-18 by type-specific HPV testing at the Week 36 visit.

  6. Percentage of Participants with No Progression of Cervical HSIL to Cervical Carcinoma from Baseline to Week 36 [ Time Frame: At Week 36 ]
    Participants will be evaluated for progression of cervical HSIL to cervical carcinoma from baseline on histology at the Week 36 visit.

  7. Percentage of Participants Who Have Cleared HPV-16 and/or HPV-18 in Non-cervical Anatomic Locations at Week 36 [ Time Frame: At Week 36 ]
    Participants will be evaluated for HPV-16 and/or HPV-18 status in specimens from non-cervical anatomic locations at the Week 36 Visit.

  8. Change from Baseline in Levels of Serum Anti-HPV-16 and Anti-HPV-18 Antibody Concentrations [ Time Frame: At baseline, Week 15, Week 36 and Week 88 ]
    Levels of anti-HPV-16 and anti-HPV-18 antibody concentrations will be measured in serum samples of participants using a standardized assay at baseline, Week 15, Week 36, and Week 88.

  9. Change from Baseline in Interferon-Gamma Response Magnitude [ Time Frame: At baseline, Week 15, Week 36 and Week 88 ]
    Peripheral blood mononuclear cells (PBMCs) will be isolated from whole blood samples collected at baseline, Week 15, Week 36 and Week 88. Assessment of cellular immune activity will be performed.

  10. Change from Baseline in Flow Cytometry Response Magnitude [ Time Frame: At baseline, Week 15 ]
    Assessment of cellular immune activity will be performed using flow cytometry.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Women aged 18 years and above
  • Confirmed cervical infection with HPV types 16 and/or 18 at screening
  • Cervical tissue specimen/slides provided to Study Pathology Adjudication Committee for diagnosis scheduled to be collected within 10 weeks prior to anticipated date of first dose of study drug
  • Confirmed histologic evidence of cervical HSIL at screening
  • Must be judged by Investigator to be an appropriate candidate for the protocol-specified procedure required at Week 36
  • With respect to their reproductive capacity must be post-menopausal or surgically sterile or willing to use a contraceptive method with failure rate of less than 1% per year when used consistently and correctly from screening until Week 36
  • Normal screening electrocardiogram (ECG)

Exclusion Criteria:

  • Microscopic or gross evidence of adenocarcinoma-in-situ (AIS), high grade vulvar, vaginal, or anal intraepithelial neoplasia or invasive cancer in any histopathologic specimen at screening
  • Cervical lesion(s) that cannot be fully visualized on colposcopy
  • History of endocervical curettage (ECC) which showed cervical HSIL indeterminate, or insufficient for diagnosis
  • Treatment for cervical HSIL within 4 weeks prior to screening
  • Pregnant, breastfeeding or considering becoming pregnant during the study
  • History of previous therapeutic HPV vaccination
  • Immunosuppression as a result of underlying illness or treatment
  • Receipt of any non-study, non-live vaccine within 2 weeks of Day 0
  • Receipt of any non-study, live vaccine within 4 weeks of Day 0
  • Current or history of clinically significant, medically unstable disease or condition which, in the judgment of the investigator, would jeopardize the safety of the participant, interfere with study assessments or endpoint evaluation, or otherwise impact the validity of the study results
  • Presence of acute or chronic bleeding or clotting disorder that would contraindicate IM injections, or use of blood thinners within 2 weeks of Day 0
  • Participation in an interventional study with an investigational compound or device within 30 days of signing informed consent
  • Less than two acceptable sites available for IM injection

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03185013


Contacts
Contact: Inovio Call Center 267-440-4237 clinical.trials@inovio.com

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Sponsors and Collaborators
Inovio Pharmaceuticals
Investigators
Study Director: Prakash Bhuyan, MD, PHD Inovio Pharmaceuticals

Additional Information:
Responsible Party: Inovio Pharmaceuticals
ClinicalTrials.gov Identifier: NCT03185013     History of Changes
Other Study ID Numbers: HPV-301
2016-002761-63 ( EudraCT Number )
First Posted: June 14, 2017    Key Record Dates
Last Update Posted: November 22, 2018
Last Verified: November 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: Yes
Device Product Not Approved or Cleared by U.S. FDA: Yes
Pediatric Postmarket Surveillance of a Device Product: No

Keywords provided by Inovio Pharmaceuticals:
Cervical intraepithelial neoplasia (CIN)
Human papillomavirus (HPV)
High grade squamous intraepithelial lesion (HSIL)
CIN 2
CIN 3
papillomavirus

Additional relevant MeSH terms:
Uterine Cervical Dysplasia
Cervical Intraepithelial Neoplasia
Squamous Intraepithelial Lesions of the Cervix
Precancerous Conditions
Neoplasms
Uterine Cervical Diseases
Uterine Diseases
Genital Diseases, Female
Carcinoma in Situ
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type