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

NCT03831503 | Completed Phase 1 FDA Drug FDA Device

• 1 other identifier: 832135
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy Volunteers

Outcome Measures

Primary Outcomes (5)

• 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.

  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.

  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.

  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.

  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

  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

Study Arms (5)

Cohort A - 0.5mg

EXPERIMENTAL

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.

Biological: INO-A002; Device: CELLECTRA® 2000; Device: Dengue Fever Antibodies (IgG)

Cohort B - 1mg

EXPERIMENTAL

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.

Biological: INO-A002; Device: CELLECTRA® 2000; Device: Dengue Fever Antibodies (IgG)

Cohort C - 2mg

EXPERIMENTAL

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.

Biological: INO-A002; Device: CELLECTRA® 2000; Device: Dengue Fever Antibodies (IgG)

Cohort D - 4mg

EXPERIMENTAL

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.

Biological: INO-A002; Device: CELLECTRA® 2000; Device: Dengue Fever Antibodies (IgG)

Cohort E - 4mg Side Port

EXPERIMENTAL

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.

Biological: INO-A002; Device: CELLECTRA® 2000; Device: Dengue Fever Antibodies (IgG)

Interventions

INO-A002 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).

Cohort A - 0.5mg; Cohort B - 1mg; Cohort C - 2mg; Cohort D - 4mg; Cohort E - 4mg Side Port

CELLECTRA® 2000 DEVICE

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

Cohort A - 0.5mg; Cohort B - 1mg; Cohort C - 2mg; Cohort D - 4mg; Cohort E - 4mg Side Port

Dengue Fever Antibodies (IgG) DEVICE

To determine if the subject is Dengue seronegative at baseline

Cohort A - 0.5mg; Cohort B - 1mg; Cohort C - 2mg; Cohort D - 4mg; Cohort E - 4mg Side Port

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may not qualify if:

• 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;

Sponsors & Collaborators

• University of Pennsylvania: lead
• Inovio Pharmaceuticals: collaborator

Study Sites (1)

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Study Officials

• Pablo Tebas, MD

  University of Pennsylvania

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: January 29, 2019
• First Posted: February 5, 2019
• Study Start: February 7, 2019
• Primary Completion: October 3, 2022
• Study Completion: October 3, 2022
• Last Updated: December 14, 2023

Record last verified: 2023-12

Locations

US (1)