ElectroPoration In a Clinical Setting
Condition: Tolerance
Study type: Interventional

Summary: 
      This is a single-blind, single-center, randomized, study in healthy subjects in which the
      volunteer patients will remain blind with respect to the voltage strength received.
    

Detailed description: 
      Background:

      The major obstacle to the preventive or therapeutic success of DNA vaccines is undoubtedly
      their delivery. If this cannot be made simple, cheap and effective, they may not become a
      viable option for human use. Numerous clinical trials have confirmed that a standard needle
      and syringe parenteral (mainly intramuscular or intradermal) delivery is not enough. An
      important tenet, confirmed by different DNA immunization studies, is that electroporation
      dramatically enhances the expression of the encoded antigen as well as the potency and
      immunogenicity of DNA vaccines. Electroporation (EP) creates transient increases in cell
      membrane permeability, thus enhancing DNA uptake and leading to a more robust immune
      response. EP involves the application of brief electric pulses to tissue in order to
      permeabilize cell membranes in a transient and reversible manner. The temporary formation of
      pores facilitate successful transport of macromolecules, like DNA, that occurs on the order
      of microseconds vs. minutes in the case of passive diffusion alone. EP is considered a safe
      and well validated procedure that can easily be handled as an out-patient procedure. In this
      regard, electrochemotherapy and electro gene transfer with the Cliniporator® (IGEA Srl,
      Carpi, Italy) has been added to clinical practice.

      Aim of the present study is therefore to formally confirm the tolerability of electroporation
      given by the EPSGT gun and the Cliniporator® device in a clinical setting of healthy
      volunteers, prior to the phase I/II study of the COVID-19 vaccine in a similar population.

      Study Design:

      Twenty (20) subjects will be randomized 1:1 to one of the following EP conditions:

        1. voltage amplitude of 40 V (10 subjects)

        2. voltage amplitude of 60 V (10 subjects). For the purpose of the study, 0.5 ml of sterile
           0.9% saline solution will be injected intramuscularly into the deltoid muscle of the
           right arm using a common insulin syringe inserted in the EPS gun; the saline injection
           will immediately be followed by electroporation given by the gun connected to the
           electrical pulse generator, Cliniporator®.

      The electroporation technology has been optimized by IGEA developing a dedicated EPS
      electrode gun. The EPS gun is an intuitive and handful procedure that combines in the same
      device the injection of a DNA vaccine (or a sterile 0.9% saline solution as in the case of
      the present study) and the delivery of the electrical pulses; the procedure is completed in
      few seconds. The EP needles 7 (diameter 0.45 mm) are hidden under a sliding cap integrated
      into the EPS gun, to reduce perceived pain potentially associated to anxiety or fear. The EPS
      gun allows the insertion of both the electrode needles and the syringe needle into the
      muscle. By pressing the syringe plunger, the content of the syringe will be injected, by
      pulling the trigger the syringe needle will be retracted, and finally the electrical pulses
      will be delivered by pressing a pedal connected to the pulse generator.

      Pain assessment:

      On the day of injection and EP, subjects will be instructed to measure the length of time
      pain is experienced by using a stopwatch. Additionally, subjects will complete the Visual
      Analog Scale (VAS) to rate the level of pain experienced immediately (0 min) and after 5 min,
      15 min, 30 min, and 60 min post-EP. In addition subjects will rate discomfort level using an
      11-point numerical rating scale (NRS), evaluated 60' (T4) after the procedure. On Day 2 and
      Day 7 post-EP, subjects will complete again the VAS as described above, and NRS. In addition,
      on Day 1 (T2, +15'), Day 2 and Day 7 subjects will complete a self-administered questionnaire
      assessing the acceptance of the procedure. Therefore, to better measure the acceptability of
      the injection related to the use of a new device from people's own perspectives, all
      participants will complete the Perception of Injection (PIN) questionnaire, adapted from the
      Vaccines' Perception of Injection (VAPI) questionnaire.

      Safety Analysis:

      Safety analyses will include summaries of the following:

        -  adverse events, including severity and relationship to the procedure (to the
           intramuscular injection, to the electroporation, or to both procedures)

        -  serious adverse events, including severity and relationship to the procedure (to the
           intramuscular injection or to the electroporation, or to both)

        -  abnormal changes in CPK

        -  abnormal changes in vital signs and ECG

      Sample size and Statistical Analysis:

      No sample size calculation was performed on this study on the tolerability of two EP voltage
      strengths.

      The statistical analyses will be mainly descriptive. Qualitative variables will be summarized
      by counts and percentages, while quantitative characteristics by quartiles or mean and
      standard deviation, as appropriate.

      Data collected longitudinally will be also described appropriately. Specific summary indices
      will be calculated on the longitudinal VAS profiles (e.g. SPID and peak PID) and the
      agreement between VAS and NRS collected at each time point will be also assessed.

      All adverse events will be graded in accordance with the 2007 FDA toxicity grading scale for
      healthy adult and adolescent volunteers enrolled in preventive vaccine clinical trials (grade
      1 = mild, grade 2 = moderate, grade 3 = severe, grade 4 = life-threatening) and will be
      reported as percentages and narratives will be also presented.

      Study Management:

      The data requested by the study will be reported in an electronic remote data capture system
      (e-CRF). The subject data collected in the e-CRF during the study will be documented
      anonymously and the subject can only be identified by an identification code.
    

Intervention name(s): Electroporation with voltage amplitude of 40 V (corresponding to an electric field strength of 100 V/cm); Electroporation with voltage amplitude of 60 V (corresponding to an electric field strength of 150 V/cm)
Intervention type(s): Device; Device
Intervention description(s): The physician will select the voltage amplitude of 40 V to be given to the subject based on a randomization list, while the subject will remain blind to the voltage he/she is assigned to. The electroporation will be performed with a EPS electrode gun.; The physician will select the voltage amplitude of 60 V to be given to the subject based on a randomization list, while the subject will remain blind to the voltage he/she is assigned to. The electroporation will be performed with a EPS electrode gun.
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Twenty (20) subjects will be randomized 1:1 to one of the following EP conditions:
voltage amplitude of 40 V (10 subjects)
voltage amplitude of 60 V (10 subjects).
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: coronavirus infection; vaccine; intramuscular electroporation