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A Study of INO-A002 in Healthy Dengue Virus-naive Adults

Primary Purpose

Healthy Volunteers

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
INO-A002
CELLECTRA® 2000
Dengue Fever Antibodies (IgG)
Sponsored by
University of Pennsylvania
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Healthy Volunteers

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesAccepts Healthy Volunteers
  1. Age 18-60 years;
  2. Able to provide consent to participate and having signed an Informed Consent Form (ICF);
  3. Able and willing to comply with all study procedures;
  4. Body mass index (BMI) between 20 and 30, inclusive
  5. Screening laboratory must be within normal limits or have only Grade 0-1 findings;
  6. Normal screening ECG or screening ECG with no clinically significant findings;
  7. Women of child-bearing potential agree to use medically effective contraception (oral contraception, barrier methods, spermicide with barrier methods, etc.) or have a partner who is sterile from enrollment to 6 months following the last injection, or have a partner who is medically unable to induce pregnancy.
  8. Sexually active men who are considered sexually fertile must agree to use either a barrier method of contraception during the study, and agree to continue the use for at least 6 months following the last injection, or have a partner who is permanently sterile or is medically unable to become pregnant;
  9. No history of clinically significant immunosuppressive or autoimmune disease. Individuals with HIV infection who have been virologically suppressed for more than 1 year and with current CD4 cell count entry greater than 500 cells/ul will be allowed into the study.
  10. No history of dengue virus vaccination or illness; no history of yellow fever vaccination.
  11. Dengue seronegative at baseline by screening laboratory evaluation
  12. Not currently or within the previous 4 weeks taking immunosuppressive agents (excluding inhaled, topical skin and/or eye drop-containing corticosteroids, low-dose methotrexate, or prednisone at a dose less than 10 mg/day or steroid dose-equivalent).

Exclusion Criteria:

  1. Administration of an investigational compound either currently or within 30 days of first dose;
  2. Previous receipt of an investigational product for the treatment or prevention of Zika virus except if participant is verified to have received placebo;
  3. Administration of any vaccine within 4 weeks of first dose;
  4. Administration of any monoclonal or polyclonal antibody product within 4 weeks of the first dose
  5. Administration of any blood product within 3 months of first dose;
  6. Pregnancy or breast feeding or plans to become pregnant during the course of the study;
  7. Positive serologic result for dengue virus (any serotype) or history of receipt of either dengue virus or yellow fever virus vaccination at any time in the past;
  8. Positive serologic test for hepatitis B surface antigen (HBsAg); or any potentially communicable infectious disease as determined by the Principal Investigator or Medical Monitor;
  9. Positive serologic test for hepatitis C (exception: successful treatment with confirmation of sustained virologic response);
  10. Baseline evidence of kidney disease as measured by creatinine greater than 1.5 (CKD Stage II or greater);
  11. Baseline screening lab(s) with Grade 2 or higher abnormality, except for Grade 2 creatinine;
  12. Chronic liver disease or cirrhosis;
  13. Immunosuppressive illness including hematologic malignancy, history of solid organ or bone marrow transplantation;
  14. Current or anticipated concomitant immunosuppressive therapy (excluding inhaled, topical skin and/or eye drop-containing corticosteroids, low-dose methotrexate, or prednisone at a dose greater than 10 mg/day or steroid dose-equivalent);
  15. Current or anticipated treatment with TNF-α inhibitors such as infliximab, adalimumab, etanercept;
  16. Prior major surgery or any radiation therapy within 4 weeks of group assignment;
  17. Any pre-excitation syndromes, e.g., Wolff-Parkinson-White syndrome;
  18. Presence of a cardiac pacemaker or automatic implantable cardioverter defibrillator (AICD)
  19. Fewer than two acceptable sites available for IM injection and EP considering the deltoid and anterolateral quadriceps muscles. The following are unacceptable sites:

    • Tattoos, keloids or hypertrophic scars located within 2 cm of intended administration site;
    • Implantable-Cardioverter-defibrillator (ICD) or pacemaker (to prevent a life-threatening arrhythmia) that is located ipsilateral to the deltoid injection site (unless deemed acceptable by a cardiologist);
    • Any metal implants or implantable medical device within the electroporation site.
  20. Prisoner or participants who are compulsorily detained (involuntary incarceration) for treatment of either a physical or psychiatric illness;
  21. Active drug or alcohol use or dependence that, in the opinion of the investigator, would interfere with adherence to study requirements or assessment of immunologic endpoints; or
  22. Not willing to allow storage and future use of samples for Zika virus related research
  23. Any illness or condition that in the opinion of the investigator may affect the safety of the participant or the evaluation of any study endpoint.
  24. Participants who plan to travel within 6 months of INO-A002 administration to a geographic location where DENV or ZIKV are currently active.
  25. Participants with known bleeding diatheses or that are using blood thinners for 30 days before study enrollment including warfarin, heparin, Clopidogrel, Apixaban (Eliquis), Dabigatran (Pradaxa), Edoxaban (Savaysa), Rivaroxaban (Xarelto). The use of low dose aspirin (81 mg daily) will be acceptable.

Sites / Locations

  • University of Pennsylvania

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

Cohort A - 0.5mg

Cohort B - 1mg

Cohort C - 2mg

Cohort D - 4mg

Cohort E - 4mg Side Port

Arm Description

Participants (n=6 per cohort) will be administered 1 injection (Day 0) of INO-A002 at 0.5 mg DNA/dose. Inoculation will be administered as 0.5 ml IM injection followed by electroporation with the CELLECTRA® 2000 device.

Participants (n=6 per cohort) will be administered 1 injection (Day 0) of INO-A002 at 1 mg DNA/dose. Inoculation will be administered as 1 ml IM injection followed by electroporation with the CELLECTRA® 2000 device.

Participants (n=6 per cohort) will be administered 2 injections (Day 0 and Day 3) of INO-A002 at 2 mg DNA/dose. Inoculation will be administered as 1 ml IM injection followed by electroporation with the CELLECTRA® 2000 device.

Participants (n=6 per cohort) will be administered 2 injections (Day 0 and Day 3) of INO-A002 at 4 mg DNA/dose. Inoculation will be administered as 1 ml IM injection followed by electroporation with the CELLECTRA® 2000 device.

Participants (n=6 per cohort) will be administered 2 injections (Day 0 and Day 3) of INO-A002 at 4 mg DNA/dose. Inoculation will be administered as 1 ml IM injection followed by electroporation with the CELLECTRA® 2000 device with Side Port needle.

Outcomes

Primary Outcome Measures

Evaluate the safety of escalating doses of INO-A002 with Hylenex® administered IM followed by electroporation with the CELLECTRA® 2000 device in healthy adult volunteers.
Safety will be assessed by monitoring the frequency and severity of adverse events utilizing the "Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials" with labs assessed as per site normal values.
Evaluate the tolerability of escalating doses of INO-A002 with Hylenex® administered IM followed by electroporation with the CELLECTRA® 2000 device in healthy adult volunteers.
Pain will be assessed by administration (i.e., injection) site reactions (frequency and severity) and visual analogue scale (VAS) scores.
Determine the maximum serum concentration (Cmax) of the monoclonal antibody dMAb-ZK190 in the serum upon administration of INO-A002 with Hylenex® delivered IM followed by electroporation.
The maximum serum concentration (Cmax) assessment will be performed by the analysis of dMAb-ZK190 levels at baseline; days 1, 3, 7 and at weeks 2, 3, 4, 5, 6, 8, 12, 16, 24 and 52. Serum concentration in micrograms/mL will be used as the measurement scale.
Determine the minimum serum concentration (Cmin) of the monoclonal antibody dMAb-ZK190 in the serum upon administration of INO-A002 with Hylenex® delivered IM followed by electroporation.
The minimum serum concentration (Cmin) assessment will be performed by the analysis of dMAb-ZK190 levels at baseline; days 1, 3, 7 and at weeks 2, 3, 4, 5, 6, 8, 12, 16, 24 and 52. Serum concentration in micrograms/mL will be used as the measurement scale.
Determine the Area Under the Curve (AUC0-t) of the monoclonal antibody dMAb-ZK190 in the serum upon administration of INO-A002 with Hylenex® delivered IM followed by electroporation
The Area Under the Curve (AUC0-t) will be performed by the analysis of dMAb-ZK190 levels at baseline; days 1, 3, 7 and at weeks 2, 3, 4, 5, 6, 8, 12, 16, 24 and 52. The Area Under the Curve (AUC0-t) against time will be calculated using the trapezoidal method.

Secondary Outcome Measures

Full Information

First Posted
January 29, 2019
Last Updated
February 17, 2023
Sponsor
University of Pennsylvania
Collaborators
Inovio Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT03831503
Brief Title
A Study of INO-A002 in Healthy Dengue Virus-naive Adults
Official Title
A Phase 1 Study of INO-A002 in Healthy Dengue Virus-naive Adults
Study Type
Interventional

2. Study Status

Record Verification Date
February 2023
Overall Recruitment Status
Completed
Study Start Date
February 7, 2019 (Actual)
Primary Completion Date
October 3, 2022 (Actual)
Study Completion Date
October 3, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Pennsylvania
Collaborators
Inovio Pharmaceuticals

4. Oversight

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
Data Monitoring Committee
No

5. Study Description

Brief Summary
Phase 1, open label, single center, dose escalation study to evaluate the safety, tolerability and pharmacokinetic profile of dMAb-ZK190 following delivery of INO-A002 with Hylenex® recombinant delivered IM followed by EP in healthy adult Dengue naïve volunteers ages 18-60 years.
Detailed Description
This is a Phase 1, open label, single center, dose escalation study to evaluate the safety, tolerability and pharmacokinetic profile of dMAb-ZK190 following delivery of INO-A002 with Hylenex® recombinant delivered IM followed by EP in healthy adult Dengue naïve volunteers ages 18-60 years. The study will apply a 3+3 design such that 3 additional subjects will be enrolled into the cohort if one DLT (Section 7.3.1) is observed in one out of the first 3 subjects dosed during the 28-day period of safety and PK assessment. If no additional DLT is observed in 3 additional subjects (i.e., 1 DLT in 6 total subjects), dosing will proceed to the subsequent cohort. However, if any additional DLT occurs (i.e., >1 DLT in 6 total subjects), then that dose will be deemed not tolerated and the prior dose will be considered the maximum tolerated dose (MTD).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Healthy Volunteers

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Model Description
This study will adhere to a dose escalation scheme. There are five cohorts for Study ZIKA-dMAb 01. Participants (n=6 per cohort) will be administered INO-A002 at four dose levels: 0.5, 1, 2, and 4 mg DNA/dose.
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
30 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Cohort A - 0.5mg
Arm Type
Experimental
Arm Description
Participants (n=6 per cohort) will be administered 1 injection (Day 0) of INO-A002 at 0.5 mg DNA/dose. Inoculation will be administered as 0.5 ml IM injection followed by electroporation with the CELLECTRA® 2000 device.
Arm Title
Cohort B - 1mg
Arm Type
Experimental
Arm Description
Participants (n=6 per cohort) will be administered 1 injection (Day 0) of INO-A002 at 1 mg DNA/dose. Inoculation will be administered as 1 ml IM injection followed by electroporation with the CELLECTRA® 2000 device.
Arm Title
Cohort C - 2mg
Arm Type
Experimental
Arm Description
Participants (n=6 per cohort) will be administered 2 injections (Day 0 and Day 3) of INO-A002 at 2 mg DNA/dose. Inoculation will be administered as 1 ml IM injection followed by electroporation with the CELLECTRA® 2000 device.
Arm Title
Cohort D - 4mg
Arm Type
Experimental
Arm Description
Participants (n=6 per cohort) will be administered 2 injections (Day 0 and Day 3) of INO-A002 at 4 mg DNA/dose. Inoculation will be administered as 1 ml IM injection followed by electroporation with the CELLECTRA® 2000 device.
Arm Title
Cohort E - 4mg Side Port
Arm Type
Experimental
Arm Description
Participants (n=6 per cohort) will be administered 2 injections (Day 0 and Day 3) of INO-A002 at 4 mg DNA/dose. Inoculation will be administered as 1 ml IM injection followed by electroporation with the CELLECTRA® 2000 device with Side Port needle.
Intervention Type
Biological
Intervention Name(s)
INO-A002
Intervention Description
Participants will receive one or two 1 ml IM injections (in different arms) into the deltoid region at day 0 (all groups), and in addition on day 3 (in the 2 mg and 4 mg cohorts).
Intervention Type
Device
Intervention Name(s)
CELLECTRA® 2000
Intervention Description
Inoculation will be followed by electroporation with the CELLECTRA® 2000 device.
Intervention Type
Device
Intervention Name(s)
Dengue Fever Antibodies (IgG)
Intervention Description
To determine if the subject is Dengue seronegative at baseline
Primary Outcome Measure Information:
Title
Evaluate the safety of escalating doses of INO-A002 with Hylenex® administered IM followed by electroporation with the CELLECTRA® 2000 device in healthy adult volunteers.
Description
Safety will be assessed by monitoring the frequency and severity of adverse events utilizing the "Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials" with labs assessed as per site normal values.
Time Frame
52 weeks
Title
Evaluate the tolerability of escalating doses of INO-A002 with Hylenex® administered IM followed by electroporation with the CELLECTRA® 2000 device in healthy adult volunteers.
Description
Pain will be assessed by administration (i.e., injection) site reactions (frequency and severity) and visual analogue scale (VAS) scores.
Time Frame
10 minutes
Title
Determine the maximum serum concentration (Cmax) of the monoclonal antibody dMAb-ZK190 in the serum upon administration of INO-A002 with Hylenex® delivered IM followed by electroporation.
Description
The maximum serum concentration (Cmax) assessment will be performed by the analysis of dMAb-ZK190 levels at baseline; days 1, 3, 7 and at weeks 2, 3, 4, 5, 6, 8, 12, 16, 24 and 52. Serum concentration in micrograms/mL will be used as the measurement scale.
Time Frame
52 weeks
Title
Determine the minimum serum concentration (Cmin) of the monoclonal antibody dMAb-ZK190 in the serum upon administration of INO-A002 with Hylenex® delivered IM followed by electroporation.
Description
The minimum serum concentration (Cmin) assessment will be performed by the analysis of dMAb-ZK190 levels at baseline; days 1, 3, 7 and at weeks 2, 3, 4, 5, 6, 8, 12, 16, 24 and 52. Serum concentration in micrograms/mL will be used as the measurement scale.
Time Frame
52 weeks
Title
Determine the Area Under the Curve (AUC0-t) of the monoclonal antibody dMAb-ZK190 in the serum upon administration of INO-A002 with Hylenex® delivered IM followed by electroporation
Description
The Area Under the Curve (AUC0-t) will be performed by the analysis of dMAb-ZK190 levels at baseline; days 1, 3, 7 and at weeks 2, 3, 4, 5, 6, 8, 12, 16, 24 and 52. The Area Under the Curve (AUC0-t) against time will be calculated using the trapezoidal method.
Time Frame
52 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Age 18-60 years; Able to provide consent to participate and having signed an Informed Consent Form (ICF); Able and willing to comply with all study procedures; Body mass index (BMI) between 20 and 30, inclusive Screening laboratory must be within normal limits or have only Grade 0-1 findings; Normal screening ECG or screening ECG with no clinically significant findings; Women of child-bearing potential agree to use medically effective contraception (oral contraception, barrier methods, spermicide with barrier methods, etc.) or have a partner who is sterile from enrollment to 6 months following the last injection, or have a partner who is medically unable to induce pregnancy. Sexually active men who are considered sexually fertile must agree to use either a barrier method of contraception during the study, and agree to continue the use for at least 6 months following the last injection, or have a partner who is permanently sterile or is medically unable to become pregnant; No history of clinically significant immunosuppressive or autoimmune disease. Individuals with HIV infection who have been virologically suppressed for more than 1 year and with current CD4 cell count entry greater than 500 cells/ul will be allowed into the study. No history of dengue virus vaccination or illness; no history of yellow fever vaccination. Dengue seronegative at baseline by screening laboratory evaluation Not currently or within the previous 4 weeks taking immunosuppressive agents (excluding inhaled, topical skin and/or eye drop-containing corticosteroids, low-dose methotrexate, or prednisone at a dose less than 10 mg/day or steroid dose-equivalent). Exclusion Criteria: Administration of an investigational compound either currently or within 30 days of first dose; Previous receipt of an investigational product for the treatment or prevention of Zika virus except if participant is verified to have received placebo; Administration of any vaccine within 4 weeks of first dose; Administration of any monoclonal or polyclonal antibody product within 4 weeks of the first dose Administration of any blood product within 3 months of first dose; Pregnancy or breast feeding or plans to become pregnant during the course of the study; Positive serologic result for dengue virus (any serotype) or history of receipt of either dengue virus or yellow fever virus vaccination at any time in the past; Positive serologic test for hepatitis B surface antigen (HBsAg); or any potentially communicable infectious disease as determined by the Principal Investigator or Medical Monitor; Positive serologic test for hepatitis C (exception: successful treatment with confirmation of sustained virologic response); Baseline evidence of kidney disease as measured by creatinine greater than 1.5 (CKD Stage II or greater); Baseline screening lab(s) with Grade 2 or higher abnormality, except for Grade 2 creatinine; Chronic liver disease or cirrhosis; Immunosuppressive illness including hematologic malignancy, history of solid organ or bone marrow transplantation; Current or anticipated concomitant immunosuppressive therapy (excluding inhaled, topical skin and/or eye drop-containing corticosteroids, low-dose methotrexate, or prednisone at a dose greater than 10 mg/day or steroid dose-equivalent); Current or anticipated treatment with TNF-α inhibitors such as infliximab, adalimumab, etanercept; Prior major surgery or any radiation therapy within 4 weeks of group assignment; Any pre-excitation syndromes, e.g., Wolff-Parkinson-White syndrome; Presence of a cardiac pacemaker or automatic implantable cardioverter defibrillator (AICD) Fewer than two acceptable sites available for IM injection and EP considering the deltoid and anterolateral quadriceps muscles. The following are unacceptable sites: Tattoos, keloids or hypertrophic scars located within 2 cm of intended administration site; Implantable-Cardioverter-defibrillator (ICD) or pacemaker (to prevent a life-threatening arrhythmia) that is located ipsilateral to the deltoid injection site (unless deemed acceptable by a cardiologist); Any metal implants or implantable medical device within the electroporation site. Prisoner or participants who are compulsorily detained (involuntary incarceration) for treatment of either a physical or psychiatric illness; Active drug or alcohol use or dependence that, in the opinion of the investigator, would interfere with adherence to study requirements or assessment of immunologic endpoints; or Not willing to allow storage and future use of samples for Zika virus related research Any illness or condition that in the opinion of the investigator may affect the safety of the participant or the evaluation of any study endpoint. Participants who plan to travel within 6 months of INO-A002 administration to a geographic location where DENV or ZIKV are currently active. Participants with known bleeding diatheses or that are using blood thinners for 30 days before study enrollment including warfarin, heparin, Clopidogrel, Apixaban (Eliquis), Dabigatran (Pradaxa), Edoxaban (Savaysa), Rivaroxaban (Xarelto). The use of low dose aspirin (81 mg daily) will be acceptable.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pablo Tebas, MD
Organizational Affiliation
University of Pennsylvania
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States

12. IPD Sharing Statement

Learn more about this trial

A Study of INO-A002 in Healthy Dengue Virus-naive Adults

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