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

NCT ID: NCT03831503

Last Updated: 2023-12-14

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

30 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-02-07

Study Completion Date

2022-10-03

Brief Summary

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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

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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).

Conditions

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Healthy Volunteers

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

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.
Primary Study Purpose

PREVENTION

Blinding Strategy

NONE

Study Groups

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Cohort A - 0.5mg

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.

Group Type EXPERIMENTAL

INO-A002

Intervention Type BIOLOGICAL

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).

CELLECTRA® 2000

Intervention Type DEVICE

Inoculation will be followed by electroporation with the CELLECTRA® 2000 device.

Dengue Fever Antibodies (IgG)

Intervention Type DEVICE

To determine if the subject is Dengue seronegative at baseline

Cohort B - 1mg

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.

Group Type EXPERIMENTAL

INO-A002

Intervention Type BIOLOGICAL

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).

CELLECTRA® 2000

Intervention Type DEVICE

Inoculation will be followed by electroporation with the CELLECTRA® 2000 device.

Dengue Fever Antibodies (IgG)

Intervention Type DEVICE

To determine if the subject is Dengue seronegative at baseline

Cohort C - 2mg

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.

Group Type EXPERIMENTAL

INO-A002

Intervention Type BIOLOGICAL

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).

CELLECTRA® 2000

Intervention Type DEVICE

Inoculation will be followed by electroporation with the CELLECTRA® 2000 device.

Dengue Fever Antibodies (IgG)

Intervention Type DEVICE

To determine if the subject is Dengue seronegative at baseline

Cohort D - 4mg

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.

Group Type EXPERIMENTAL

INO-A002

Intervention Type BIOLOGICAL

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).

CELLECTRA® 2000

Intervention Type DEVICE

Inoculation will be followed by electroporation with the CELLECTRA® 2000 device.

Dengue Fever Antibodies (IgG)

Intervention Type DEVICE

To determine if the subject is Dengue seronegative at baseline

Cohort E - 4mg Side Port

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.

Group Type EXPERIMENTAL

INO-A002

Intervention Type BIOLOGICAL

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).

CELLECTRA® 2000

Intervention Type DEVICE

Inoculation will be followed by electroporation with the CELLECTRA® 2000 device.

Dengue Fever Antibodies (IgG)

Intervention Type DEVICE

To determine if the subject is Dengue seronegative at baseline

Interventions

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INO-A002

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 BIOLOGICAL

CELLECTRA® 2000

Inoculation will be followed by electroporation with the CELLECTRA® 2000 device.

Intervention Type DEVICE

Dengue Fever Antibodies (IgG)

To determine if the subject is Dengue seronegative at baseline

Intervention Type DEVICE

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

60 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Inovio Pharmaceuticals

INDUSTRY

Sponsor Role collaborator

University of Pennsylvania

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Pablo Tebas, MD

Role: PRINCIPAL_INVESTIGATOR

University of Pennsylvania

Locations

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University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status

Countries

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United States

Other Identifiers

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832135

Identifier Type: -

Identifier Source: org_study_id