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

December 13, 2023 updated by: University of Pennsylvania

A Phase 1 Study of INO-A002 in Healthy Dengue Virus-naive Adults

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.

Study Overview

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).

Study Type

Interventional

Enrollment (Actual)

30

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • University of Pennsylvania

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 60 years (Adult)

Accepts Healthy Volunteers

Yes

Description

  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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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.
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).
Inoculation will be followed by electroporation with the CELLECTRA® 2000 device.
To determine if the subject is Dengue seronegative at baseline
Experimental: 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.
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).
Inoculation will be followed by electroporation with the CELLECTRA® 2000 device.
To determine if the subject is Dengue seronegative at baseline
Experimental: 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.
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).
Inoculation will be followed by electroporation with the CELLECTRA® 2000 device.
To determine if the subject is Dengue seronegative at baseline
Experimental: 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.
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).
Inoculation will be followed by electroporation with the CELLECTRA® 2000 device.
To determine if the subject is Dengue seronegative at baseline
Experimental: 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.
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).
Inoculation will be followed by electroporation with the CELLECTRA® 2000 device.
To determine if the subject is Dengue seronegative at baseline

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Time Frame: 52 weeks
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.
52 weeks
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.
Time Frame: 10 minutes
Pain will be assessed by administration (i.e., injection) site reactions (frequency and severity) and visual analogue scale (VAS) scores.
10 minutes
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.
Time Frame: 52 weeks
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.
52 weeks
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.
Time Frame: 52 weeks
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.
52 weeks
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
Time Frame: 52 weeks
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.
52 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Collaborators

Investigators

  • Principal Investigator: Pablo Tebas, MD, University of Pennsylvania

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 7, 2019

Primary Completion (Actual)

October 3, 2022

Study Completion (Actual)

October 3, 2022

Study Registration Dates

First Submitted

January 29, 2019

First Submitted That Met QC Criteria

February 4, 2019

First Posted (Actual)

February 5, 2019

Study Record Updates

Last Update Posted (Estimated)

December 14, 2023

Last Update Submitted That Met QC Criteria

December 13, 2023

Last Verified

December 1, 2023

More Information

Terms related to this study

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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