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

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.)

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.

Study Overview

• Status: Completed
• Conditions: Hantaan Virus
• Intervention / Treatment: Biological: Hantaan Vaccine:; Biological: Puumala Vaccine; Biological: Hantaan/Puumala Vaccine

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Silver Spring, Maryland, United States, 20910
      • WRAIR Clinical Trials Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 49 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Hantaan Vaccine: 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: DNA Vaccine 2.0 mg/1 mL phosphate-buffered saline
EXPERIMENTAL: Puumala Vaccine: 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; DNA Vaccine 2.0 mg/1 mL phosphate-buffered saline
EXPERIMENTAL: Hantaan/Puumala Vaccine; 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; DNA Vaccine 2.0 mg/1 mL phosphate-buffered saline

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: U.S. Army Medical Research and Development Command
• Investigators: Principal Investigator: Kristopher Paolino, MD, Walter Reed Army Institute of Research (WRAIR)

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 30, 2016
• Primary Completion (ACTUAL): September 27, 2017
• Study Completion (ACTUAL): September 27, 2017

Study Registration Dates

• First Submitted: May 13, 2016
• First Submitted That Met QC Criteria: May 17, 2016
• First Posted (ESTIMATE): May 18, 2016

Study Record Updates

• Last Update Posted (ACTUAL): February 16, 2021
• Last Update Submitted That Met QC Criteria: February 10, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Virus Diseases; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: S-15-40; WRAIR 2289 (OTHER: WRAIR)