A Single-blind Study to Evaluate the Safety, Tolerability, and Immunogenicity of a Hantaan Puumala Virus DNA Vaccine

Study Overview
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Brief Summary
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This is a single-center, randomized, single-blinded study of the Hantaan virus HTNV DNA vaccine alone, Puumala virus PUUV DNA vaccine alone, and mixed Hantaan/Puumala HTNV/PUUV DNA vaccines delivered intramuscularly IM by the needle-free PharmaJet Stratus DSJI device.

Detailed Description
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Investigational HTNV and PUUV DNA vaccines, manufactured in accordance with cGMP guidelines by Ajinomoto Bio-Pharma Services (California), from their respective drug substances, pWRG/HTN-M(co) and pWRG/PUU-M(s2),were constructed on a well-characterized plasmid backbone, pWRG7077. These plasmid DNA vaccines will be delivered IM using the needle-free, disposable syringe jet injection device (PharmaJet Stratis). Subjects will be randomized into 3 groups of 9 subjects each for a total of 27 subjects. Each subject will receive a total of 3 vaccinations. Group 1 vaccine will consist of 2 administrations of 1 mg of HTN plasmid (left and right deltoid) for a total of 2 mg/vaccination. Group 2 vaccine will consist of 2 administrations of 1 mg of PUU plasmid (left, right deltoid) for a total of 2 mg/vaccination. Group 3 vaccine will consist of a 1:1 mixture of HTNM and PUU vaccines (left, right deltoid) for a total of 2 mg/vaccination (1 mg/vaccination of each DNA). Vaccinations will be administered on Days 0, 28, and 56. There will be an optional 4th vaccination on Day 168 dependent on subject availability for the additional follow-up visit on Day 196, tolerability of the vaccinations to date, and investigator discretion. Volunteers will be invited back for the 4th vaccination to determine if a booster dose results in increased immunogenicity and seroconversion. All subjects will be followed until Day 252 (9 months). A Day 365 follow-up visit, for an immunogenicity draw only, may be requested dependent on immunogenicity results shortly after this final date, generally within 4 weeks of the Day 252 visit or once the assays can be completed. Subjects may be allowed to receive other licensed vaccinations or enroll in other clinical trials after the Day 252 visit.

Official Title
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Hantaan Virus Plasmid DNA Vaccine (Expressing Gn and Gc Antigens; E. Coli) [HTNV Vaccine] and Puumala Virus Plasmid DNA Vaccine (Expressing Gn and Gc Antigens; E. Coli; Ajinomoto Bio-Pharma Services) [PUUV Vaccine] Administered Via Stratus Needle-free Injection System (PharmaJet, Inc.)

Conditions
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Hantaan Virus

Intervention / Treatment
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* Biological: Hantaan Vaccine:
* Biological: Puumala Vaccine
* Biological: Hantaan/Puumala Vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy adult male or nonpregnant, nonlactating 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 not abstinent, are known to be at least 1 year post-menopausal (defined as no menses for 12 consecutive months) or willing to use an effective method of contraception (eg, hormonal contraception to include oral and implantable options, diaphragm, cervical cap, intrauterine device, condom, or anatomical sterility [self or partner]) for the duration of study participation (from the date of screening) until at least 3 months after the last injection Negative hantavirus PsVNA test result at screening Exclusion Criteria: History or serologic evidence of prior infection with any hantavirus or prior participation in an 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 (subjects continuing through Day 365 will not join other new studies until their final visit) Receipt of licensed vaccines within 14 days before or after immunization (30 days for live vaccines) 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, 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 Blood donation for human use (eg, American Red Cross or other similar blood drives) within the 56 days preceding study entry or planned administration during the study period Any confirmed 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 For corticosteroids, this will mean prednisone, or equivalent, greater than or equal to 0.5 mg/kg/day Intranasal, inhaled, and topical steroids are allowed (daily inhaled steroids for treatment of asthma are NOT allowed) Any chronic or active neurologic disorder, including seizures and epilepsy, excluding a single febrile seizure as a child 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 49 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Study will enroll 3 randomized groups of 9 subjects for a total of 27 subjects. Every subject will receive a total of 3 vaccinations. Subjects will be blinded to the group they are randomized to. Each vaccination consists of 2 administrations of 1 mg (left/right deltoid) for a total of 2 mg/vaccination. Group 1 will be vaccinated with the HTNV vaccine, pWRG/HTN-M (co). Group 2 will be vaccinated with the PUUV vaccine, pWRG/PUU-M (s2). Group 3 will be vaccinated with a combined HTNV/PUUV vaccines. Each group will be vaccinated on Days 0, 28, and 56. An optional 4th vaccination on Day 168 with follow-up on Day 196. All doses will be administered with PharmaJet Stratis device. All subjects to be followed until at least 3 months post last vaccination with Day 252 the final study visit (a 12-month, optional follow-up visit may be requested approximately on Day 365). Subjects will complete postinjection memory aids for 7 days after each vaccination.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Hantaan Vaccine:<br>1 mg in 0.5 mL per administration, 2 administrations per vaccination, total injected volume 1 mL per vaccination (for 2.0 mg dose) | Biological: Hantaan Vaccine:<br>* DNA Vaccine 2.0 mg/1 mL phosphate-buffered saline<br>|
| Experimental: Puumala Vaccine:<br>1 mg in 0.5 mL per administration, 2 administrations per vaccination, total injected volume 1 mL per vaccination (for 2.0 mg dose) | Biological: Puumala Vaccine<br>* DNA Vaccine 2.0 mg/1 mL phosphate-buffered saline<br>|
| Experimental: Hantaan/Puumala Vaccine<br>The HTNV and PUUV vaccine will be combined (equal volumes) before use: 1 mg in 0.5 mL per administration, 2 administrations per vaccination, total injected volume 1 mL per vaccination (for 2.0 mg dose) | Biological: Hantaan/Puumala Vaccine<br>* DNA Vaccine 2.0 mg/1 mL phosphate-buffered saline<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hantaan Vaccine: Number of Adverse Events | Number of adverse events. | 365 days | 
| Puumala Vaccine: Number of Adverse Events | Number of adverse events. | 365 days | 
| Hantaan/Puumala Vaccine: Number of Adverse Events | Number of adverse events. | 365 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hantaan Vaccine (50) immunogenicity | Pseudovirion neutralization assay 50% titer | 365 days | 
| Puumala Vaccine (50) immunogenicity | Pseudovirion neutralization assay 50% titer | 365 days | 
| Hantaan/Puumala Vaccin (50) immunogenicity | Pseudovirion neutralization assay 50% titer | 365 days | 
| Hantaan Vaccine (80) immunogenicity | Pseudovirion neutralization assay 80% titer | 365 days | 
| Puumala Vaccine (80) immunogenicity | Pseudovirion neutralization assay 80% titer | 365 days | 
| Hantaan/Puumala Vaccin (80) immunogenicity | Pseudovirion neutralization assay 80% titer | 365 days | 
| Hantaan Vaccine (80) immunogenicity | Plaque-reduction neutralization test (PRNT) comparing Day 0 to Day 84 | 84 days | 
| Puumala Vaccine (80) immunogenicity | Plaque-reduction neutralization test (PRNT) comparing Day 0 to Day 84 | 84 days | 
| Hantaan/Puumala Vaccin (80) immunogenicity | Plaque-reduction neutralization test (PRNT) comparing Day 0 to Day 84 | 84 days |