Phase 2a Immunogenicity Study of Hantaan/Puumala Virus DNA Vaccine for Prevention of Hemorrhagic Fever
Condition: Hemorrhagic Fever With Renal Syndrome
MeSH terms: Hemorrhagic Fevers, Viral; Hemorrhagic Fever with Renal Syndrome; Syndrome; Fever
Intervention: HTNV/PUUV DNA vaccine; Placebo; TriGrid Delivery System (TDS)
Intervention description: HTNV/PUUV DNA vaccine mixture, composed of pWRG/HTN-M(co) and pWRG/PUU-M(s2); 0.9% sodium chloride; The TDS-IM is an integrated, fully automated clinical EP system designed for delivering DNA-based vaccines and therapies to target tissues, through temporary disruption of cellular membranes via electrical pulses
Intervention MeSH terms: Vaccines
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 130.0
Sex: All
Minimum age: 18 Years
Maximum age: 49 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Hantaan virus; Puumala virus; HFRS

Summary:

      The purpose of this study is to compare the immune responses of two different doses (1.0 mg
      and 2.0 mg) and two different dosing schedules (two doses or three doses) of a mixed Hantaan
      virus (HTNV) and Puumala virus (PUUV) DNA vaccine in healthy participants. To maintain a
      blind, participants in the two-dose group will receive one dose of normal saline placebo. All
      of the groups will also receive a booster dose 6 months after first vaccination. The results
      will help to determine which dose and vaccination schedule will be best to move forward in
      the vaccine development process.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Healthy adult male or non-pregnant, non-lactating female, ages 18-49 (inclusive) at
             the time of screening

          -  Have provided written informed consent before screening

          -  Free of clinically significant health problems, as determined by pertinent medical
             history and clinical examination prior to entry into the study

          -  Available and able to participate for all study visits and procedures

          -  Females, if sexually active, are known to be at least one year post-menopausal
             (defined as no menses for 12 consecutive months), or willing to use an effective
             method of contraception (eg, hormonal contraception, diaphragm, cervical cap,
             intrauterine device, condom, anatomical sterility [self or partner]) from the date of
             screening until at least 3 months after the last injection

          -  Negative hantavirus pseudovirion neutralization assay (PsVNA) test result at screening

        Exclusion Criteria:

          -  History or serologic evidence of prior infection with any hantavirus virus, or prior
             participation in a HTNV or PUUV vaccine trial

          -  History of severe local or systemic reactions to any vaccination or a history of
             severe allergic reactions

          -  Ongoing participation in another clinical trial

          -  Receipt or planned receipt of any vaccination, experimental or otherwise within the
             period 30 days prior to the first injection through the period 60 days after Study Day
             168 (booster dose; approximately 9 month period in total), with the exception of
             emergency use vaccinations as needed

          -  Individuals in whom a skinfold measurement of the cutaneous and subcutaneous tissue
             for all eligible injection sites (deltoid region) exceeds 40 mm

          -  Individuals in whom the ability to observe possible local reactions at the eligible
             injections sites (deltoid region) is, in the opinion of the investigator, unacceptably
             obscured due to a physical condition or permanent body art

          -  Acute or chronic, clinically significant hematologic, pulmonary, cardiovascular, or
             hepatic or renal functional abnormality as determined by the investigator based on
             medical history, physical exam, electrocardiogram (ECG), and/or laboratory screening
             test

          -  Pregnant or lactating female, or female who intends to become pregnant during the
             study period

          -  Administration of immunoglobulins and/or any blood products within the 120 days
             preceding study entry or planned administration during the study period

          -  Any serologic evidence of hepatitis B or C infection

          -  Any confirmed or suspected immunosuppressive or immunodeficient condition, including
             human immunodeficiency virus (HIV) infection

          -  Administration of chronic (defined as more than 14 days) immunosuppressants or other
             immune modifying drugs within 6 months of study entry

               1. For corticosteroids, this will mean prednisone, or equivalent, greater than or
                  equal to 0.5 mg/kg/day

               2. Intranasal and topical steroids are allowed

          -  Any chronic or active neurologic disorder, including seizures and epilepsy, excluding
             a single febrile seizure as a child

          -  Syncopal episode within 12 months of screening

          -  Suspected or known current alcohol and/or illicit drug abuse

          -  Unwilling to allow storage and use of blood for future hantavirus-related research

          -  Any other significant finding that in the opinion of the investigator would increase
             the risk of the individual having an adverse outcome from participating in this study