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Study of HPV Specific Immunotherapy in Participants With HPV Associated Head and Neck Squamous Cell Carcinoma

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ClinicalTrials.gov Identifier: NCT02163057
Recruitment Status : Completed
First Posted : June 13, 2014
Results First Posted : December 23, 2020
Last Update Posted : January 22, 2021
Sponsor:
Collaborator:
University of Pennsylvania
Information provided by (Responsible Party):
Inovio Pharmaceuticals

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Head and Neck Squamous Cell Cancer
Interventions Biological: INO-3112
Device: CELLECTRA™-5P
Enrollment 22
Recruitment Details Participants with a diagnosis of HPV associated head and neck squamous cell carcinoma were enrolled in the study between 13th August 2014 to 23rd January 2017.
Pre-assignment Details  
Arm/Group Title Cohort 1: Surgery Cohort Cohort 2: Chemoradiation
Hide Arm/Group Description Participants received up to two doses of INO-3112 immunotherapy 3 weeks (± 3 days) apart before surgery and up to three doses of INO-3112 immunotherapy 3 weeks (± 3 days) apart after surgery for a total of no more than four doses of INO-3112 immunotherapy delivered IM followed by EP with CELLECTRA™-5P device. Participants received four doses of INO-3112 immunotherapy delivered IM followed by EP with CELLECTRA™-5P device 3 weeks (± 3 days) apart beginning approximately 2 to 6 months after chemoradiation therapy.
Period Title: Overall Study
Started 6 16
Completed 3 11
Not Completed 3 5
Reason Not Completed
Participant Refusal to Continue             2             2
Participant Significant Noncompliance             0             1
Progression of Disease             1             2
Arm/Group Title Cohort 1: Surgery Cohort Cohort 2: Chemoradiation Total
Hide Arm/Group Description Participants received up to two doses of INO-3112 immunotherapy 3 weeks (± 3 days) apart before surgery and up to three doses of INO-3112 immunotherapy 3 weeks (± 3 days) apart after surgery for a total of no more than four doses of INO-3112 immunotherapy delivered IM followed by EP with CELLECTRA™-5P device. Participants received four doses of INO-3112 immunotherapy delivered IM followed by EP with CELLECTRA™-5P device 3 weeks (± 3 days) apart beginning approximately 2 to 6 months after chemoradiation therapy. Total of all reporting groups
Overall Number of Baseline Participants 6 16 22
Hide Baseline Analysis Population Description
Safety population included all participants who received at least one dose of study treatment plus EP.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 6 participants 16 participants 22 participants
62.2  (4.26) 55.4  (10.26) 57.3  (9.43)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants 16 participants 22 participants
Female
0
   0.0%
2
  12.5%
2
   9.1%
Male
6
 100.0%
14
  87.5%
20
  90.9%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants 16 participants 22 participants
Hispanic or Latino
0
   0.0%
0
   0.0%
0
   0.0%
Not Hispanic or Latino
6
 100.0%
16
 100.0%
22
 100.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants 16 participants 22 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
1
  16.7%
2
  12.5%
3
  13.6%
White
5
  83.3%
14
  87.5%
19
  86.4%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
1.Primary Outcome
Title Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Event (SAEs)
Hide Description An adverse event (AE) is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body, or worsening of a pre-existing condition, temporally associated with the use of a product whether or not considered related to the use of the product. TEAE is defined as any AE with onset after the administration of study medication through the end-of-study follow-up, or any event that was present at baseline but worsened in intensity or was subsequently considered treatment-related by the Investigator through the end of the study. Serious adverse event (SAE) is defined as an event that meets 1 of the following criteria: is fatal or life-threatening, results in persistent or significant disability or incapacity, constitutes a congenital anomaly or birth defect, is clinically meaningful or requires inpatient hospitalization or prolongation of existing hospitalization.
Time Frame Up to 6 months post last dose
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population included all participants who received at least one dose of study treatment plus EP.
Arm/Group Title Cohort 1: Surgery Cohort Cohort 2: Chemoradiation
Hide Arm/Group Description:
Participants received up to two doses of INO-3112 immunotherapy 3 weeks (± 3 days) apart before surgery and up to three doses of INO-3112 immunotherapy 3 weeks (± 3 days) apart after surgery for a total of no more than four doses of INO-3112 immunotherapy delivered IM followed by EP with CELLECTRA™-5P device.
Participants received four doses of INO-3112 immunotherapy delivered IM followed by EP with CELLECTRA™-5P device 3 weeks (± 3 days) apart beginning approximately 2 to 6 months after chemoradiation therapy.
Overall Number of Participants Analyzed 6 16
Measure Type: Count of Participants
Unit of Measure: Participants
At least 1 TEAE
6
 100.0%
15
  93.8%
At least 1 Treatment-emergent SAE
2
  33.3%
0
   0.0%
2.Secondary Outcome
Title E6 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by Enzyme-linked Immunosorbent Assay (ELISA)
Hide Description Titers for HPV-16 and HPV-18 E6- and E7-specific antibodies were assessed by ELISA.
Time Frame Up to 6 months post last dose
Hide Outcome Measure Data
Hide Analysis Population Description
Assigned Number of Doses (ANoD) population included all participants who received their assigned number of doses of study treatment plus EP. Number analyzed is the number of participants with data available for analysis at a specified time-point.
Arm/Group Title Cohort 1: Surgery Cohort Cohort 2: Chemoradiation
Hide Arm/Group Description:
Participants received up to two doses of INO-3112 immunotherapy 3 weeks (± 3 days) apart before surgery and up to three doses of INO-3112 immunotherapy 3 weeks (± 3 days) apart after surgery for a total of no more than four doses of INO-3112 immunotherapy delivered IM followed by EP with CELLECTRA™ device.
Participants received four doses of INO-3112 immunotherapy delivered IM followed by EP with CELLECTRA™ device 3 weeks (± 3 days) apart beginning approximately 2 to 6 months after chemoradiation therapy.
Overall Number of Participants Analyzed 5 15
Mean (Standard Deviation)
Unit of Measure: log titer
HPV-16 ELISA titer, 1st dose Number Analyzed 4 participants 11 participants
3.6  (4.53) 0.4  (1.18)
HPV-16 ELISA titer, 2nd dose Number Analyzed 4 participants 13 participants
2.2  (2.61) 0.0  (0.00)
HPV-16 ELISA titer, 3rd dose Number Analyzed 5 participants 13 participants
2.6  (2.39) 1.2  (2.33)
HPV-16 ELISA titer, 4th dose Number Analyzed 5 participants 12 participants
2.4  (3.44) 1.0  (2.42)
HPV-16 ELISA titer, Week 2 post last dose Number Analyzed 4 participants 12 participants
2.8  (3.48) 2.3  (2.91)
HPV-16 ELISA titer, 1st long term follow-up Number Analyzed 4 participants 12 participants
1.3  (2.51) 1.0  (2.42)
HPV-16 ELISA titer, 2nd long term follow-up Number Analyzed 5 participants 10 participants
0.0  (0.00) 1.2  (2.63)
HPV-16 ELISA titer, 3rd long term follow-up Number Analyzed 2 participants 9 participants
0.0  (0.00) 0.8  (2.40)
HPV-16 ELISA titer, 4th long term follow-up Number Analyzed 2 participants 6 participants
0.0  (0.00) 1.4  (3.39)
HPV-16 ELISA titer, 5th long term follow-up Number Analyzed 2 participants 3 participants
0.0  (0.00) 0.0  (0.00)
HPV-16 ELISA titer, 6th long term follow-up Number Analyzed 0 participants 2 participants
3.1  (4.32)
HPV-16 ELISA titer, initial surgery Number Analyzed 5 participants 0 participants
1.0  (2.24)
HPV-16 ELISA titer, surgery Number Analyzed 4 participants 0 participants
0.0  (0.00)
HPV-16 ELISA titer, follow-up Week 2 post-surgery Number Analyzed 3 participants 0 participants
4.6  (1.27)
HPV-16 ELISA titer, optional surgery Number Analyzed 1 participants 0 participants
0.0 [1]   (NA)
HPV-16 ELISA titer, unscheduled visit Number Analyzed 1 participants 0 participants
3.9 [1]   (NA)
HPV-16 ELISA titer, end of study follow-up Number Analyzed 4 participants 12 participants
0.0  (0.00) 0.0  (0.00)
HPV-18 ELISA titer, 1st dose Number Analyzed 4 participants 11 participants
0.0  (0.00) 0.4  (1.18)
HPV-18 ELISA titer, 2nd dose Number Analyzed 4 participants 13 participants
0.0  (0.00) 0.7  (1.69)
HPV-18 ELISA titer, 3rd dose Number Analyzed 5 participants 13 participants
0.0  (0.00) 0.8  (1.88)
HPV-18 ELISA titer, 4th dose Number Analyzed 5 participants 12 participants
1.0  (2.24) 1.2  (2.12)
HPV-18 ELISA titer, Week 2 post last dose Number Analyzed 4 participants 12 participants
0.0  (0.00) 3.0  (3.25)
HPV-18 ELISA titer, 1st long term follow-up Number Analyzed 4 participants 12 participants
1.3  (2.51) 2.0  (3.04)
HPV-18 ELISA titer, 2nd long term follow-up Number Analyzed 5 participants 10 participants
1.0  (2.24) 1.3  (2.09)
HPV-18 ELISA titer, 3rd long term follow-up Number Analyzed 2 participants 9 participants
0.0  (0.00) 1.1  (2.28)
HPV-18 ELISA titer, 4th long term follow-up Number Analyzed 2 participants 6 participants
0.0  (0.00) 1.7  (2.68)
HPV-18 ELISA titer, 5th long term follow-up Number Analyzed 2 participants 3 participants
0.0  (0.00) 1.7  (2.89)
HPV-18 ELISA titer, 6th long term follow-up Number Analyzed 0 participants 2 participants
6.1  (0.00)
HPV-18 ELISA titer, initial surgery Number Analyzed 5 participants 0 participants
0.0  (0.00)
HPV-18 ELISA titer, surgery Number Analyzed 4 participants 0 participants
0.0  (0.00)
HPV-18 ELISA titer, follow-up Week 2 post-surgery Number Analyzed 3 participants 0 participants
0.0  (0.00)
HPV-18 ELISA titer, optional surgery Number Analyzed 1 participants 0 participants
0.0 [1]   (NA)
HPV-18 ELISA titer, unscheduled visit Number Analyzed 1 participants 0 participants
0.0 [1]   (NA)
HPV-18 ELISA titer, end of study follow-up Number Analyzed 4 participants 12 participants
1.5  (3.05) 2.8  (3.01)
[1]
Standard deviation could not be calculated due to an insufficient number of participants.
3.Secondary Outcome
Title E7 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by ELISA
Hide Description Titers for HPV-16 and HPV-18 E6- and E7-specific antibodies were assessed by ELISA.
Time Frame Up to 6 months post last dose
Hide Outcome Measure Data
Hide Analysis Population Description
ANoD population included all participants who received their assigned number of doses of study treatment plus EP. Number analyzed is the number of participants with data available for analysis at a specified time-point.
Arm/Group Title Cohort 1: Surgery Cohort Cohort 2: Chemoradiation
Hide Arm/Group Description:
Participants received up to two doses of INO-3112 immunotherapy 3 weeks (± 3 days) apart before surgery and up to three doses of INO-3112 immunotherapy 3 weeks (± 3 days) apart after surgery for a total of no more than four doses of INO-3112 immunotherapy delivered IM followed by EP with CELLECTRA™-5P device.
Participants received four doses of INO-3112 immunotherapy delivered IM followed by EP with CELLECTRA™-5P device 3 weeks (± 3 days) apart beginning approximately 2 to 6 months after chemoradiation therapy.
Overall Number of Participants Analyzed 5 15
Mean (Standard Deviation)
Unit of Measure: log titer
HPV-16, 1st dose Number Analyzed 4 participants 11 participants
0.0  (0.00) 0.4  (1.18)
HPV-16 ELISA titer, 2nd dose Number Analyzed 4 participants 13 participants
0.0  (0.00) 0.5  (1.69)
HPV-16 ELISA titer, 3rd dose Number Analyzed 5 participants 13 participants
1.2  (2.73) 2.1  (2.85)
HPV-16 ELISA titer, 4th dose Number Analyzed 5 participants 12 participants
3.0  (3.06) 3.0  (3.41)
HPV-16 ELISA titer, Week 2 post last dose Number Analyzed 4 participants 12 participants
2.8  (3.48) 3.3  (4.09)
HPV-16 ELISA titer, 1st long term follow-up Number Analyzed 4 participants 12 participants
2.5  (3.03) 2.8  (3.63)
HPV-16 ELISA titer, 2nd long term follow-up Number Analyzed 5 participants 10 participants
0.8  (1.75) 1.6  (3.28)
HPV-16 ELISA titer, 3rd long term follow-up Number Analyzed 2 participants 9 participants
0.0  (0.00) 1.5  (3.24)
HPV-16 ELISA titer, 4th long term follow-up Number Analyzed 2 participants 6 participants
0.0  (0.00) 0.8  (2.05)
HPV-16 ELISA titer, 5th long term follow-up Number Analyzed 2 participants 3 participants
0.0  (0.00) 3.1  (5.43)
HPV-16 ELISA titer, 6th long term follow-up Number Analyzed 0 participants 2 participants
4.2  (5.87)
HPV-16 ELISA titer, initial surgery Number Analyzed 5 participants 0 participants
0.0  (0.00)
HPV-16 ELISA titer, surgery Number Analyzed 4 participants 0 participants
0.0  (0.00)
HPV-16 ELISA titer, follow-up Week 2 post-surgery Number Analyzed 3 participants 0 participants
0.0  (0.00)
HPV-16 ELISA titer, optional surgery Number Analyzed 1 participants 0 participants
0.0 [1]   (NA)
HPV-16 ELISA titer, unscheduled visit Number Analyzed 1 participants 0 participants
0.0 [1]   (NA)
HPV-16 ELISA titer, end of study follow-up Number Analyzed 4 participants 12 participants
0.0  (0.00) 1.3  (2.45)
HPV-18 ELISA titer, 1st dose Number Analyzed 4 participants 11 participants
0.0  (0.00) 0.5  (1.51)
HPV-18 ELISA titer, 2nd dose Number Analyzed 4 participants 13 participants
2.5  (2.89) 0.3  (1.08)
HPV-18 ELISA titer, 3rd dose Number Analyzed 5 participants 13 participants
2.7  (3.67) 1.3  (2.03)
HPV-18 ELISA titer, 4th dose Number Analyzed 5 participants 12 participants
4.5  (4.17) 3.0  (3.21)
HPV-18 ELISA titer, Week 2 post last dose Number Analyzed 4 participants 12 participants
8.0  (1.65) 4.2  (2.83)
HPV-18 ELISA titer, 1st long term follow-up Number Analyzed 4 participants 12 participants
6.9  (2.44) 4.5  (3.41)
HPV-18 ELISA titer, 2nd long term follow-up Number Analyzed 5 participants 10 participants
5.8  (3.98) 1.8  (3.13)
HPV-18 ELISA titer, 3rd long term follow-up Number Analyzed 2 participants 9 participants
2.0  (2.77) 3.1  (3.79)
HPV-18 ELISA titer, 4th long term follow-up Number Analyzed 2 participants 6 participants
0.0  (0.00) 2.5  (2.83)
HPV-18 ELISA titer, 5th long term follow-up Number Analyzed 2 participants 3 participants
0.0  (0.00) 5.5  (4.80)
HPV-18 ELISA titer, 6th long term follow-up Number Analyzed 0 participants 2 participants
8.3  (0.00)
HPV-18 ELISA titer, initial surgery Number Analyzed 5 participants 0 participants
0.0  (0.00)
HPV-18 ELISA titer, surgery Number Analyzed 4 participants 0 participants
2.4  (4.70)
HPV-18 ELISA titer, follow-up Week 2 post-surgery Number Analyzed 3 participants 0 participants
1.3  (2.26)
HPV-18 ELISA titer, optional surgery Number Analyzed 1 participants 0 participants
0.0 [1]   (NA)
HPV-18 ELISA titer, unscheduled visit Number Analyzed 1 participants 0 participants
0.0 [1]   (NA)
HPV-18 ELISA titer, end of study follow-up Number Analyzed 4 participants 12 participants
4.4  (5.29) 4.6  (3.03)
[1]
Standard deviation could not be calculated due to an insufficient number of participants.
4.Secondary Outcome
Title Change From Baseline (CFB) in Combined HPV-16 and HPV-18 E6 and E7 Antigen-Specific Spot-Forming Units Per Million Peripheral Blood Mononuclear Cell (SFU/10^6 PBMC) as Assessed by Enzyme-Linked Immunosorbent Spot-Forming Assay (ELISpot)
Hide Description [Not Specified]
Time Frame Baseline up to 6 months post last dose
Hide Outcome Measure Data
Hide Analysis Population Description
ANoD population included all participants who received their assigned number of doses of study treatment plus EP. Number analyzed is the number of participants with data available for analysis at a specified time-point.
Arm/Group Title Cohort 1: Surgery Cohort Cohort 2: Chemoradiation
Hide Arm/Group Description:
Participants received up to two doses of INO-3112 immunotherapy 3 weeks (± 3 days) apart before surgery and up to three doses of INO-3112 immunotherapy 3 weeks (± 3 days) apart after surgery for a total of no more than four doses of INO-3112 immunotherapy delivered IM followed by EP with CELLECTRA™-5P device.
Participants received four doses of INO-3112 immunotherapy delivered IM followed by EP with CELLECTRA™-5P device 3 weeks (± 3 days) apart beginning approximately 2 to 6 months after chemoradiation therapy.
Overall Number of Participants Analyzed 5 15
Mean (Standard Deviation)
Unit of Measure: SFU/10^6 PBMC
Baseline Number Analyzed 5 participants 15 participants
20.3  (22.65) 11.7  (10.25)
CFB at 2nd dose Number Analyzed 4 participants 13 participants
24.2  (34.56) 96.9  (118.41)
CFB at 3rd dose Number Analyzed 4 participants 15 participants
15.0  (17.54) 158.9  (231.73)
CFB at 4th dose Number Analyzed 5 participants 13 participants
50.3  (49.06) 263.6  (597.80)
CFB at Week 2 post last dose Number Analyzed 4 participants 14 participants
68.3  (63.98) 354.7  (632.29)
CFB at 1st long term follow-up Number Analyzed 4 participants 11 participants
182.2  (211.31) 128.8  (132.05)
CFB at 2nd long term follow-up Number Analyzed 5 participants 7 participants
102.3  (140.03) 151.1  (94.32)
CFB at 3rd long term follow-up Number Analyzed 2 participants 7 participants
127.6  (3.46) 113.2  (153.59)
CFB at 4th long term follow-up Number Analyzed 1 participants 4 participants
41.4 [1]   (NA) 29.8  (28.11)
CFB at 5th long term follow-up Number Analyzed 2 participants 1 participants
129.1  (19.87) 0.0 [1]   (NA)
CFB at 6th long term follow-up Number Analyzed 1 participants 1 participants
141.7 [1]   (NA) 11.7 [1]   (NA)
CFB at follow-up Week 2 post-surgery Number Analyzed 2 participants 0 participants
154.2  (168.50)
CFB at end of study follow-up Number Analyzed 4 participants 9 participants
50.0  (42.75) 70.5  (87.09)
[1]
Standard deviation could not be calculated due to an insufficient number of participants.
5.Secondary Outcome
Title Change From Baseline (CFB) in CD8+ T-Cell Responses Specific for HPV-16 as Assessed by Flow Cytometry
Hide Description A flow cytometry assay called "lytic granule loading" was used to analyze CD8+ T cells specific for HPV-16 and CD8+ T cells specific for HPV-18 by evaluating the following markers: CD8, granzyme A (GrzA), granzyme B (GrzB), and perforin (Prf) co-expression with CD137, CD69, or CD38.
Time Frame At baseline and Week 2 post last dose
Hide Outcome Measure Data
Hide Analysis Population Description
ANoD population included all participants who received their assigned number of doses of study treatment plus EP. Number analyzed is the number of participants with data available for analysis at a specified time-point.
Arm/Group Title Cohort 1: Surgery Cohort Cohort 2: Chemoradiation
Hide Arm/Group Description:
Participants received up to two doses of INO-3112 immunotherapy 3 weeks (± 3 days) apart before surgery and up to three doses of INO-3112 immunotherapy 3 weeks (± 3 days) apart after surgery for a total of no more than four doses of INO-3112 immunotherapy delivered IM followed by EP with CELLECTRA™-5P device.
Participants received four doses of INO-3112 immunotherapy delivered IM followed by EP with CELLECTRA™-5P device 3 weeks (± 3 days) apart beginning approximately 2 to 6 months after chemoradiation therapy.
Overall Number of Participants Analyzed 5 15
Mean (Standard Deviation)
Unit of Measure: cells/million T-cells
CD8+CD137+GrzA+GrzB+Prf+, baseline Number Analyzed 2 participants 6 participants
0.09  (0.124) 0.02  (0.039)
CD8+CD137+GrzA+GrzB+Prf+,CFB Week 2 post last dose Number Analyzed 2 participants 6 participants
0.16  (0.230) 0.11  (0.188)
CD8+CD69+GrzA+GrzB+Prf+, baseline Number Analyzed 2 participants 6 participants
0.00  (0.000) 0.17  (0.345)
CD8+CD69+GrzA+GrzB+Prf+, CFB Week 2 post last dose Number Analyzed 2 participants 6 participants
0.48  (0.282) 0.20  (0.471)
CD8+CD38+GrzA+GrzB+Prf+, baseline Number Analyzed 2 participants 6 participants
0.00  (0.000) 0.14  (0.163)
CD8+CD38+GrzA+GrzB+Prf+, CFB Week 2 post last dose Number Analyzed 2 participants 6 participants
0.89  (0.457) 0.26  (0.555)
6.Secondary Outcome
Title Change From Baseline (CFB) in CD8+ T-Cell Responses Specific for HPV-18 as Assessed by Flow Cytometry
Hide Description A flow cytometry assay called "lytic granule loading" was used to analyze CD8+ T cells specific for HPV-16 and CD8+ T cells specific for HPV-18 by evaluating the following markers: CD8, granzyme A (GrzA), granzyme B (GrzB), and perforin (Prf) co-expression with CD137, CD69, or CD38.
Time Frame At baseline and Week 2 post last dose
Hide Outcome Measure Data
Hide Analysis Population Description
ANoD population included all participants who received their assigned number of doses of study treatment plus EP. Number analyzed is the number of participants with data available for analysis at a specified time-point.
Arm/Group Title Cohort 1: Surgery Cohort Cohort 2: Chemoradiation
Hide Arm/Group Description:
Participants received up to two doses of INO-3112 immunotherapy 3 weeks (± 3 days) apart before surgery and up to three doses of INO-3112 immunotherapy 3 weeks (± 3 days) apart after surgery for a total of no more than four doses of INO-3112 immunotherapy delivered IM followed by EP with CELLECTRA™-5P device.
Participants received four doses of INO-3112 immunotherapy delivered IM followed by EP with CELLECTRA™-5P device 3 weeks (± 3 days) apart beginning approximately 2 to 6 months after chemoradiation therapy.
Overall Number of Participants Analyzed 5 15
Mean (Standard Deviation)
Unit of Measure: cells/million T-cells
CD8+CD137+GrzA+GrzB+Prf+, baseline Number Analyzed 2 participants 6 participants
0.00  (0.000) 0.05  (0.070)
CD8+CD137+GrzA+GrzB+Prf+,CFB Week 2 post last dose Number Analyzed 2 participants 6 participants
0.09  (0.073) 0.07  (0.089)
CD8+CD69+GrzA+GrzB+Prf+, baseline Number Analyzed 2 participants 6 participants
0.00  (0.000) 0.10  (0.158)
CD8+CD69+GrzA+GrzB+Prf+, CFB Week 2 post last dose Number Analyzed 2 participants 6 participants
0.20  (0.283) 0.34  (0.540)
CD8+CD38+GrzA+GrzB+Prf+, baseline Number Analyzed 2 participants 6 participants
0.00  (0.000) 0.06  (0.135)
CD8+CD38+GrzA+GrzB+Prf+, CFB Week 2 post last dose Number Analyzed 2 participants 6 participants
0.73  (0.841) 0.36  (0.552)
7.Secondary Outcome
Title Mean Difference in Tumor Infiltrating Lymphocytes (TILs) in Presurgical and Surgical Tumor Tissue Samples of Cohort I as Assessed by Immunohistochemistry (IHC)
Hide Description The difference in means (post-surgery minus screening) for tumor-infiltrating lymphocytes (TILs) such as CD8, FoxP3, and perforin was analyzed using immunohistochemistry staining techniques.
Time Frame At screening and post-surgery
Hide Outcome Measure Data
Hide Analysis Population Description
ANoD population included all participants who received their assigned number of doses of study treatment plus EP.
Arm/Group Title Cohort 1: Surgery Cohort
Hide Arm/Group Description:
Participants received up to two doses of INO-3112 immunotherapy 3 weeks (± 3 days) apart before surgery and up to three doses of INO-3112 immunotherapy 3 weeks (± 3 days) apart after surgery for a total of no more than four doses of INO-3112 immunotherapy delivered IM followed by EP with CELLECTRA™-5P device.
Overall Number of Participants Analyzed 4
Mean (95% Confidence Interval)
Unit of Measure: positive cells per square millimeter
CD8
268.5
(-1583.5 to 2120.5)
FoxP3
-79.8
(-834.2 to 674.7)
Perforin
9.5
(-0.4 to 19.4)
8.Secondary Outcome
Title Mean Difference in CD8/FoxP3 Ratio in Presurgical and Surgical Tumor Tissue Samples of Cohort I as Assessed by Immunohistochemistry (IHC)
Hide Description The difference in means (post-surgery minus screening) for the CD8/FoxP3 ratio was analyzed using immunohistochemistry staining techniques.
Time Frame At screening and post-surgery
Hide Outcome Measure Data
Hide Analysis Population Description
ANoD population included all participants who received their assigned number of doses of study treatment plus EP.
Arm/Group Title Cohort 1: Surgery Cohort
Hide Arm/Group Description:
Participants received up to two doses of INO-3112 immunotherapy 3 weeks (± 3 days) apart before surgery and up to three doses of INO-3112 immunotherapy 3 weeks (± 3 days) apart after surgery for a total of no more than four doses of INO-3112 immunotherapy delivered IM followed by EP with CELLECTRA™-5P device.
Overall Number of Participants Analyzed 4
Mean (95% Confidence Interval)
Unit of Measure: ratio
0.2
(-0.8 to 1.2)
9.Secondary Outcome
Title Phenotype of Cultured TILs
Hide Description [Not Specified]
Time Frame Up to 6 months post last dose
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Data was not collected due to lack of recoverable samples sufficient for analysis
Arm/Group Title Cohort 1: Surgery Cohort Cohort 2: Chemoradiation
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Participants received up to two doses of INO-3112 immunotherapy 3 weeks (± 3 days) apart before surgery and up to three doses of INO-3112 immunotherapy 3 weeks (± 3 days) apart after surgery for a total of no more than four doses of INO-3112 immunotherapy delivered IM followed by EP with CELLECTRA™ device.
Participants received four doses of INO-3112 immunotherapy delivered IM followed by EP with CELLECTRA™ device 3 weeks (± 3 days) apart beginning approximately 2 to 6 months after chemoradiation therapy.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
Time Frame Up to 6 months post last dose
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Cohort 1: Surgery Cohort Cohort 2: Chemoradiation
Hide Arm/Group Description Participants received up to two doses of INO-3112 immunotherapy 3 weeks (± 3 days) apart before surgery and up to three doses of INO-3112 immunotherapy 3 weeks (± 3 days) apart after surgery for a total of no more than four doses of INO-3112 immunotherapy delivered IM followed by EP with CELLECTRA™-5P device. Participants received four doses of INO-3112 immunotherapy delivered IM followed by EP with CELLECTRA™-5P device 3 weeks (± 3 days) apart beginning approximately 2 to 6 months after chemoradiation therapy.
All-Cause Mortality
Cohort 1: Surgery Cohort Cohort 2: Chemoradiation
Affected / at Risk (%) Affected / at Risk (%)
Total   0/6 (0.00%)   0/16 (0.00%) 
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Cohort 1: Surgery Cohort Cohort 2: Chemoradiation
Affected / at Risk (%) Affected / at Risk (%)
Total   2/6 (33.33%)   0/16 (0.00%) 
Immune system disorders     
Anaphylactic reaction  1  1/6 (16.67%)  0/16 (0.00%) 
Injury, poisoning and procedural complications     
Post procedural haemorrhage  1  1/6 (16.67%)  0/16 (0.00%) 
Metabolism and nutrition disorders     
Decreased appetite  1  1/6 (16.67%)  0/16 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Skin neoplasm bleeding  1  1/6 (16.67%)  0/16 (0.00%) 
Renal and urinary disorders     
Acute kidney injury  1  1/6 (16.67%)  0/16 (0.00%) 
1
Term from vocabulary, MedDRA Version 20.0
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Cohort 1: Surgery Cohort Cohort 2: Chemoradiation
Affected / at Risk (%) Affected / at Risk (%)
Total   6/6 (100.00%)   15/16 (93.75%) 
Ear and labyrinth disorders     
Tinnitus  1  1/6 (16.67%)  1/16 (6.25%) 
Endocrine disorders     
Hypothyroidism  1  1/6 (16.67%)  1/16 (6.25%) 
Thyroiditis  1  1/6 (16.67%)  0/16 (0.00%) 
Eye disorders     
Diplopia  1  1/6 (16.67%)  0/16 (0.00%) 
Retinal Detachment  1  1/6 (16.67%)  0/16 (0.00%) 
Gastrointestinal disorders     
Dry Mouth  1  2/6 (33.33%)  1/16 (6.25%) 
Dysphagia  1  3/6 (50.00%)  1/16 (6.25%) 
Eructation  1  0/6 (0.00%)  1/16 (6.25%) 
Gastrooesophageal Reflux Disease  1  0/6 (0.00%)  3/16 (18.75%) 
Glossodynia  1  1/6 (16.67%)  0/16 (0.00%) 
Hypoaesthesia Oral  1  1/6 (16.67%)  0/16 (0.00%) 
Nausea  1  1/6 (16.67%)  0/16 (0.00%) 
Odynophagia  1  1/6 (16.67%)  0/16 (0.00%) 
Oral Discomfort  1  0/6 (0.00%)  1/16 (6.25%) 
Oral Pain  1  0/6 (0.00%)  1/16 (6.25%) 
Salivary Duct Inflammation  1  1/6 (16.67%)  0/16 (0.00%) 
Stomatitis  1  0/6 (0.00%)  1/16 (6.25%) 
Tongue Discolouration  1  1/6 (16.67%)  0/16 (0.00%) 
Tongue Oedema  1  1/6 (16.67%)  0/16 (0.00%) 
Toothache  1  1/6 (16.67%)  0/16 (0.00%) 
General disorders     
Chest Pain  1  0/6 (0.00%)  1/16 (6.25%) 
Fatigue  1  2/6 (33.33%)  1/16 (6.25%) 
Injection Site Bruising  1  2/6 (33.33%)  3/16 (18.75%) 
Injection Site Erythema  1  2/6 (33.33%)  5/16 (31.25%) 
Injection Site Induration  1  0/6 (0.00%)  1/16 (6.25%) 
Injection Site Pain  1  5/6 (83.33%)  10/16 (62.50%) 
Injection Site Swelling  1  1/6 (16.67%)  4/16 (25.00%) 
Localised Oedema  1  2/6 (33.33%)  0/16 (0.00%) 
Mucosal Inflammation  1  1/6 (16.67%)  1/16 (6.25%) 
Immune system disorders     
Seasonal Allergy  1  0/6 (0.00%)  1/16 (6.25%) 
Infections and infestations     
Epididymitis  1  0/6 (0.00%)  1/16 (6.25%) 
Folliculitis  1  1/6 (16.67%)  0/16 (0.00%) 
Furuncle  1  2/6 (33.33%)  0/16 (0.00%) 
Herpes Zoster  1  1/6 (16.67%)  0/16 (0.00%) 
Oral Candidiasis  1  1/6 (16.67%)  2/16 (12.50%) 
Oral Herpes  1  1/6 (16.67%)  0/16 (0.00%) 
Staphylococcal Infection  1  1/6 (16.67%)  0/16 (0.00%) 
Upper Respiratory Tract Infection  1  1/6 (16.67%)  0/16 (0.00%) 
Urinary Tract Infection  1  0/6 (0.00%)  1/16 (6.25%) 
Viral Upper Respiratory Tract Infection  1  1/6 (16.67%)  1/16 (6.25%) 
Injury, poisoning and procedural complications     
Ankle Fracture  1  0/6 (0.00%)  1/16 (6.25%) 
Procedural Pain  1  1/6 (16.67%)  0/16 (0.00%) 
Investigations     
Blood Creatinine Increased  1  1/6 (16.67%)  0/16 (0.00%) 
Weight Decreased  1  2/6 (33.33%)  2/16 (12.50%) 
Metabolism and nutrition disorders     
Decreased Appetite  1  2/6 (33.33%)  1/16 (6.25%) 
Dyslipidaemia  1  0/6 (0.00%)  1/16 (6.25%) 
Hypomagnesaemia  1  1/6 (16.67%)  0/16 (0.00%) 
Hyponatraemia  1  1/6 (16.67%)  0/16 (0.00%) 
Musculoskeletal and connective tissue disorders     
Joint Range Of Motion Decreased  1  0/6 (0.00%)  1/16 (6.25%) 
Muscle Spasms  1  0/6 (0.00%)  1/16 (6.25%) 
Muscle Twitching  1  1/6 (16.67%)  0/16 (0.00%) 
Musculoskeletal Pain  1  1/6 (16.67%)  1/16 (6.25%) 
Musculoskeletal Stiffness  1  1/6 (16.67%)  1/16 (6.25%) 
Myalgia  1  0/6 (0.00%)  1/16 (6.25%) 
Neck Pain  1  2/6 (33.33%)  0/16 (0.00%) 
Pain In Extremity  1  0/6 (0.00%)  1/16 (6.25%) 
Pain In Jaw  1  0/6 (0.00%)  1/16 (6.25%) 
Trigger Finger  1  0/6 (0.00%)  1/16 (6.25%) 
Trismus  1  1/6 (16.67%)  0/16 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Melanocytic Naevus  1  0/6 (0.00%)  1/16 (6.25%) 
Nervous system disorders     
Dizziness  1  1/6 (16.67%)  1/16 (6.25%) 
Dysgeusia  1  2/6 (33.33%)  1/16 (6.25%) 
Hypoaesthesia  1  0/6 (0.00%)  2/16 (12.50%) 
Neuropathy Peripheral  1  1/6 (16.67%)  1/16 (6.25%) 
Paraesthesia  1  0/6 (0.00%)  2/16 (12.50%) 
Peripheral Sensory Neuropathy  1  0/6 (0.00%)  1/16 (6.25%) 
Restless Legs Syndrome  1  0/6 (0.00%)  1/16 (6.25%) 
Psychiatric disorders     
Depression  1  1/6 (16.67%)  0/16 (0.00%) 
Renal and urinary disorders     
Haematuria  1  0/6 (0.00%)  1/16 (6.25%) 
Respiratory, thoracic and mediastinal disorders     
Cough  1  1/6 (16.67%)  0/16 (0.00%) 
Dysphonia  1  3/6 (50.00%)  0/16 (0.00%) 
Dyspnoea Exertional  1  1/6 (16.67%)  0/16 (0.00%) 
Oropharyngeal Pain  1  1/6 (16.67%)  0/16 (0.00%) 
Pharyngeal Oedema  1  1/6 (16.67%)  0/16 (0.00%) 
Pleuritic Pain  1  0/6 (0.00%)  1/16 (6.25%) 
Productive Cough  1  1/6 (16.67%)  0/16 (0.00%) 
Skin and subcutaneous tissue disorders     
Alopecia Areata  1  0/6 (0.00%)  1/16 (6.25%) 
Dermatitis Contact  1  0/6 (0.00%)  1/16 (6.25%) 
Dry Skin  1  0/6 (0.00%)  1/16 (6.25%) 
Erythema  1  1/6 (16.67%)  0/16 (0.00%) 
Night Sweats  1  0/6 (0.00%)  1/16 (6.25%) 
Rash Maculo-Papular  1  1/6 (16.67%)  0/16 (0.00%) 
Rash Papular  1  0/6 (0.00%)  1/16 (6.25%) 
Skin Fibrosis  1  1/6 (16.67%)  0/16 (0.00%) 
Skin Lesion  1  0/6 (0.00%)  1/16 (6.25%) 
Surgical and medical procedures     
Skin Neoplasm Excision  1  0/6 (0.00%)  1/16 (6.25%) 
Vascular disorders     
Arteriosclerosis  1  0/6 (0.00%)  1/16 (6.25%) 
Hypertension  1  1/6 (16.67%)  0/16 (0.00%) 
Hypotension  1  1/6 (16.67%)  0/16 (0.00%) 
1
Term from vocabulary, MedDRA Version 20.0
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
 
Results Point of Contact
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Name/Title: Study Director
Organization: Inovio Pharmaceuticals
Phone: 267-440-4237
EMail: clinical.trials@inovio.com
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Responsible Party: Inovio Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02163057    
Other Study ID Numbers: HPV-005
First Submitted: June 10, 2014
First Posted: June 13, 2014
Results First Submitted: December 1, 2020
Results First Posted: December 23, 2020
Last Update Posted: January 22, 2021