Hemorrhagic Fever With Renal Syndrome
Conditions
Keywords
Hantaan virus, Puumala virus, HFRS
Brief 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.
Detailed description
The study will enroll 4 randomized groups of 30 subjects each for a total of 120 subjects. These groups will be split so that 60 individuals receive the 1.0 mg dose and the other 60 receive the 2.0 mg dose. Every subject will receive a total of 3 injections on Days 0, 28, and 56. Half of each of these groups (n = 30) will receive 2 vaccine injections at Days 0 and 56 (normal saline placebo on Day 28) while the other half will receive 3 vaccine injections at Days 0, 28, and 56. All subjects will receive a booster dose at Day 168 to help assess immunogenicity with this booster dose. All doses will be administered with the TDS-IM device. All subjects will be followed until at least Day 252 (a 12 month follow-up visit may be requested). Subjects will complete post-injection memory aids for 7 days after each injection. There will also be up to 12 alternates enrolled and used to replace any original subject who fails to complete all 3 scheduled primary injections and Day 70 follow-up visit.
Interventions
BIOLOGICALHTNV/PUUV DNA vaccine
HTNV/PUUV DNA vaccine mixture, composed of pWRG/HTN-M(co) and pWRG/PUU-M(s2)
BIOLOGICALPlacebo
0.9% sodium chloride
DEVICETriGrid Delivery System (TDS)
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
Sponsors
Walter Reed Army Institute of Research (WRAIR)
Ichor Medical Systems Incorporated
United States Army Medical Materiel Development Activity
US Army Medical Research Institute of Infectious Diseases
U.S. Army Medical Research and Development Command
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 49 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA50 | Study Days 0 to 365 | The primary endpoint will be to determine the seroconversion rates of the vaccines. Seroconversion is defined as production of neutralizing antibody titers measured using a pseudovirion neutralization assay (PsVNA). A PsVNA50 titer ≥ 20 is considered positive. Sera were collected on Days 0, 28, 56, 84, 140, 168, 196, 252, 365 and evaluated for the presence of neutralizing antibodies using PsVNA50. Percentages for seroconversion are based on the number of subjects presenting non-missing data. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Solicited Adverse Events (AEs) in Study Subjects | The time of each injection through 14 days following the procedure | The nature, frequency, and severity of solicited adverse events (AE) occurring from the time of each injection through 14 days following the procedure. The total number of events counts all solicited adverse events for all subjects. Subjects may have more than one solicited adverse event per body system and preferred term. |
| Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA80 | Study Days 0 to 365 | Seroconversion is defined as production of neutralizing antibody titers measured using a pseudovirion neutralization assay (PsVNA). Sera were collected on Days 0, 28, 56, 84, 140, 168, 196, 252, 365 and evaluated for the presence of neutralizing antibodies by using PsVNA80. Percentages for seroconversion are based on the number of subjects presenting non-missing data. |
Countries
United States
Participant flow
Recruitment details
A total of 130 subjects were enrolled in the study. Ten of the 130 were enrolled as replacements for early withdrawals. The first participant was enrolled on July 9, 2014 and the last participant was enrolled in September 2015.
Participants by arm
| Arm | Count |
|---|---|
| Vaccine + Placebo at 1.0 mg 1.0 mg HTNV/PUUV DNA vaccine IM-EP via TriGrid™ Delivery System (TDS) on Study Day 0, 56 and 168. 1.0 mg placebo administration on Study Day 28.
HTNV/PUUV DNA vaccine: HTNV/PUUV DNA vaccine mixture, composed of pWRG/HTN-M(co) and pWRG/PUU-M(s2)
Placebo: 0.9% sodium chloride
TriGrid Delivery System (TDS): 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 | 31 |
| Vaccine at 1.0 mg 1.0 mg HTNV/PUUV DNA vaccine IM-EP via TriGrid™ Delivery System (TDS) on Study Day 0, 28, 56 and 168.
HTNV/PUUV DNA vaccine: HTNV/PUUV DNA vaccine mixture, composed of pWRG/HTN-M(co) and pWRG/PUU-M(s2)
TriGrid Delivery System (TDS): 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 | 33 |
| Vaccine + Placebo at 2.0 mg 2.0 mg HTNV/PUUV DNA vaccine IM-EP via TriGrid™ Delivery System (TDS) on Study Day 0, 56 and 168. 2.0 mg placebo administration on Study Day 28.
HTNV/PUUV DNA vaccine: HTNV/PUUV DNA vaccine mixture, composed of pWRG/HTN-M(co) and pWRG/PUU-M(s2)
Placebo: 0.9% sodium chloride
TriGrid Delivery System (TDS): 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 | 33 |
| Vaccine at 2.0 mg 2.0 mg HTNV/PUUV DNA vaccine IM-EP via TriGrid™ Delivery System (TDS) on Study Day 0, 28, 56 and 168.
HTNV/PUUV DNA vaccine: HTNV/PUUV DNA vaccine mixture, composed of pWRG/HTN-M(co) and pWRG/PUU-M(s2)
TriGrid Delivery System (TDS): 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 | 33 |
| Total | 130 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Exclusion criteria | 0 | 0 | 1 | 0 |
| Overall Study | Lost to Follow-up | 0 | 2 | 1 | 2 |
| Overall Study | Physician Decision | 0 | 1 | 1 | 1 |
| Overall Study | Withdrawal by Subject | 2 | 4 | 1 | 3 |
Baseline characteristics
| Characteristic | Vaccine + Placebo at 1.0 mg | Total | Vaccine at 2.0 mg | Vaccine + Placebo at 2.0 mg | Vaccine at 1.0 mg |
|---|---|---|---|---|---|
| Age, Customized Age | 34.3 years STANDARD_DEVIATION 8.8 | 32.2 years STANDARD_DEVIATION 8.3 | 33.2 years STANDARD_DEVIATION 8.5 | 30.5 years STANDARD_DEVIATION 6.6 | 30.9 years STANDARD_DEVIATION 8.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 11 Participants | 1 Participants | 3 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 29 Participants | 119 Participants | 32 Participants | 30 Participants | 28 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 2 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 4 Participants | 2 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 20 Participants | 66 Participants | 15 Participants | 14 Participants | 17 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 6 Participants | 3 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 11 Participants | 51 Participants | 13 Participants | 14 Participants | 13 Participants |
| Region of Enrollment United States | 31 participants | 130 participants | 33 participants | 33 participants | 33 participants |
| Sex: Female, Male Female | 15 Participants | 63 Participants | 18 Participants | 13 Participants | 17 Participants |
| Sex: Female, Male Male | 16 Participants | 67 Participants | 15 Participants | 20 Participants | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 31 | 0 / 33 | 0 / 33 | 0 / 33 |
| other Total, other adverse events | 29 / 31 | 33 / 33 | 31 / 33 | 33 / 33 |
| serious Total, serious adverse events | 0 / 31 | 0 / 33 | 1 / 33 | 0 / 33 |
Outcome results
Primary
Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA50
The primary endpoint will be to determine the seroconversion rates of the vaccines. Seroconversion is defined as production of neutralizing antibody titers measured using a pseudovirion neutralization assay (PsVNA). A PsVNA50 titer ≥ 20 is considered positive. Sera were collected on Days 0, 28, 56, 84, 140, 168, 196, 252, 365 and evaluated for the presence of neutralizing antibodies using PsVNA50. Percentages for seroconversion are based on the number of subjects presenting non-missing data.
Time frame: Study Days 0 to 365
Population: Of the 130 subjects enrolled, 120 met the conditions for the efficacy evaluable population, that is subjects who received all three of the vaccinations on Study Days 0, 28, and 56; and who attended at least one subsequent study visit. Seroconversion is measured in the efficacy evaluable population.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Vaccine + Placebo at 1.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA50 | Seroconversion at Day 28 | Seroconversion | 1 Participants |
| Vaccine + Placebo at 1.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA50 | Seroconversion at Day 84 | Seroconversion | 15 Participants |
| Vaccine + Placebo at 1.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA50 | Seroconversion at Day 252 | No Seroconversion | 17 Participants |
| Vaccine + Placebo at 1.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA50 | Seroconversion at Day 140 | Seroconversion | 11 Participants |
| Vaccine + Placebo at 1.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA50 | Seroconversion at Day 28 | No Seroconversion | 29 Participants |
| Vaccine + Placebo at 1.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA50 | Seroconversion at Day 84 | No Seroconversion | 15 Participants |
| Vaccine + Placebo at 1.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA50 | Seroconversion at Day 252 | Seroconversion | 12 Participants |
| Vaccine + Placebo at 1.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA50 | Seroconversion at Day 168 | No Seroconversion | 18 Participants |
| Vaccine + Placebo at 1.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA50 | Seroconversion at Day 56 | No Seroconversion | 29 Participants |
| Vaccine + Placebo at 1.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA50 | Seroconversion at Day 365 | Seroconversion | 12 Participants |
| Vaccine + Placebo at 1.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA50 | Seroconversion at Day 196 | No Seroconversion | 12 Participants |
| Vaccine + Placebo at 1.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA50 | Seroconversion at Day 56 | Seroconversion | 1 Participants |
| Vaccine + Placebo at 1.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA50 | Seroconversion at Day 168 | Seroconversion | 12 Participants |
| Vaccine + Placebo at 1.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA50 | Seroconversion at Day 365 | No Seroconversion | 8 Participants |
| Vaccine + Placebo at 1.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA50 | Seroconversion at Day 196 | Seroconversion | 18 Participants |
| Vaccine + Placebo at 1.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA50 | Seroconversion at Day 140 | No Seroconversion | 19 Participants |
| Vaccine at 1.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA50 | Seroconversion at Day 56 | No Seroconversion | 20 Participants |
| Vaccine at 1.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA50 | Seroconversion at Day 252 | Seroconversion | 16 Participants |
| Vaccine at 1.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA50 | Seroconversion at Day 252 | No Seroconversion | 10 Participants |
| Vaccine at 1.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA50 | Seroconversion at Day 365 | Seroconversion | 15 Participants |
| Vaccine at 1.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA50 | Seroconversion at Day 365 | No Seroconversion | 7 Participants |
| Vaccine at 1.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA50 | Seroconversion at Day 84 | Seroconversion | 18 Participants |
| Vaccine at 1.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA50 | Seroconversion at Day 84 | No Seroconversion | 12 Participants |
| Vaccine at 1.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA50 | Seroconversion at Day 28 | No Seroconversion | 29 Participants |
| Vaccine at 1.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA50 | Seroconversion at Day 140 | Seroconversion | 14 Participants |
| Vaccine at 1.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA50 | Seroconversion at Day 140 | No Seroconversion | 14 Participants |
| Vaccine at 1.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA50 | Seroconversion at Day 28 | Seroconversion | 1 Participants |
| Vaccine at 1.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA50 | Seroconversion at Day 168 | Seroconversion | 11 Participants |
| Vaccine at 1.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA50 | Seroconversion at Day 168 | No Seroconversion | 16 Participants |
| Vaccine at 1.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA50 | Seroconversion at Day 196 | Seroconversion | 23 Participants |
| Vaccine at 1.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA50 | Seroconversion at Day 56 | Seroconversion | 10 Participants |
| Vaccine at 1.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA50 | Seroconversion at Day 196 | No Seroconversion | 3 Participants |
| Vaccine + Placebo at 2.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA50 | Seroconversion at Day 252 | Seroconversion | 19 Participants |
| Vaccine + Placebo at 2.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA50 | Seroconversion at Day 56 | Seroconversion | 1 Participants |
| Vaccine + Placebo at 2.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA50 | Seroconversion at Day 196 | Seroconversion | 20 Participants |
| Vaccine + Placebo at 2.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA50 | Seroconversion at Day 168 | Seroconversion | 7 Participants |
| Vaccine + Placebo at 2.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA50 | Seroconversion at Day 365 | Seroconversion | 16 Participants |
| Vaccine + Placebo at 2.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA50 | Seroconversion at Day 252 | No Seroconversion | 10 Participants |
| Vaccine + Placebo at 2.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA50 | Seroconversion at Day 196 | No Seroconversion | 9 Participants |
| Vaccine + Placebo at 2.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA50 | Seroconversion at Day 84 | No Seroconversion | 16 Participants |
| Vaccine + Placebo at 2.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA50 | Seroconversion at Day 168 | No Seroconversion | 22 Participants |
| Vaccine + Placebo at 2.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA50 | Seroconversion at Day 84 | Seroconversion | 14 Participants |
| Vaccine + Placebo at 2.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA50 | Seroconversion at Day 365 | No Seroconversion | 6 Participants |
| Vaccine + Placebo at 2.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA50 | Seroconversion at Day 140 | Seroconversion | 9 Participants |
| Vaccine + Placebo at 2.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA50 | Seroconversion at Day 28 | No Seroconversion | 29 Participants |
| Vaccine + Placebo at 2.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA50 | Seroconversion at Day 56 | No Seroconversion | 29 Participants |
| Vaccine + Placebo at 2.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA50 | Seroconversion at Day 28 | Seroconversion | 1 Participants |
| Vaccine + Placebo at 2.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA50 | Seroconversion at Day 140 | No Seroconversion | 20 Participants |
| Vaccine at 2.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA50 | Seroconversion at Day 168 | No Seroconversion | 13 Participants |
| Vaccine at 2.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA50 | Seroconversion at Day 28 | Seroconversion | 2 Participants |
| Vaccine at 2.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA50 | Seroconversion at Day 28 | No Seroconversion | 28 Participants |
| Vaccine at 2.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA50 | Seroconversion at Day 56 | Seroconversion | 7 Participants |
| Vaccine at 2.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA50 | Seroconversion at Day 56 | No Seroconversion | 23 Participants |
| Vaccine at 2.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA50 | Seroconversion at Day 84 | Seroconversion | 17 Participants |
| Vaccine at 2.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA50 | Seroconversion at Day 84 | No Seroconversion | 13 Participants |
| Vaccine at 2.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA50 | Seroconversion at Day 140 | Seroconversion | 12 Participants |
| Vaccine at 2.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA50 | Seroconversion at Day 140 | No Seroconversion | 16 Participants |
| Vaccine at 2.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA50 | Seroconversion at Day 168 | Seroconversion | 13 Participants |
| Vaccine at 2.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA50 | Seroconversion at Day 196 | Seroconversion | 19 Participants |
| Vaccine at 2.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA50 | Seroconversion at Day 196 | No Seroconversion | 8 Participants |
| Vaccine at 2.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA50 | Seroconversion at Day 252 | Seroconversion | 16 Participants |
| Vaccine at 2.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA50 | Seroconversion at Day 252 | No Seroconversion | 11 Participants |
| Vaccine at 2.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA50 | Seroconversion at Day 365 | Seroconversion | 14 Participants |
| Vaccine at 2.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA50 | Seroconversion at Day 365 | No Seroconversion | 6 Participants |
Secondary
Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA80
Seroconversion is defined as production of neutralizing antibody titers measured using a pseudovirion neutralization assay (PsVNA). Sera were collected on Days 0, 28, 56, 84, 140, 168, 196, 252, 365 and evaluated for the presence of neutralizing antibodies by using PsVNA80. Percentages for seroconversion are based on the number of subjects presenting non-missing data.
Time frame: Study Days 0 to 365
Population: Of the 130 subjects enrolled, 120 met the conditions for the efficacy evaluable population, that is subjects who received all three of the vaccinations on Study Days 0, 28, and 56; and who attended at least one subsequent study visit. Seroconversion is measured in the efficacy evaluable population.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Vaccine + Placebo at 1.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA80 | Seroconversion at Day 365 | No Seroconversion | 15 Participants |
| Vaccine + Placebo at 1.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA80 | Seroconversion at Day 56 | No Seroconversion | 30 Participants |
| Vaccine + Placebo at 1.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA80 | Seroconversion at Day 196 | No Seroconversion | 16 Participants |
| Vaccine + Placebo at 1.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA80 | Seroconversion at Day 140 | Seroconversion | 2 Participants |
| Vaccine + Placebo at 1.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA80 | Seroconversion at Day 28 | Seroconversion | 0 Participants |
| Vaccine + Placebo at 1.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA80 | Seroconversion at Day 84 | Seroconversion | 5 Participants |
| Vaccine + Placebo at 1.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA80 | Seroconversion at Day 168 | No Seroconversion | 26 Participants |
| Vaccine + Placebo at 1.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA80 | Seroconversion at Day 84 | No Seroconversion | 25 Participants |
| Vaccine + Placebo at 1.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA80 | Seroconversion at Day 252 | No Seroconversion | 23 Participants |
| Vaccine + Placebo at 1.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA80 | Seroconversion at Day 196 | Seroconversion | 14 Participants |
| Vaccine + Placebo at 1.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA80 | Seroconversion at Day 365 | Seroconversion | 5 Participants |
| Vaccine + Placebo at 1.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA80 | Seroconversion at Day 56 | Seroconversion | 0 Participants |
| Vaccine + Placebo at 1.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA80 | Seroconversion at Day 168 | Seroconversion | 4 Participants |
| Vaccine + Placebo at 1.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA80 | Seroconversion at Day 252 | Seroconversion | 6 Participants |
| Vaccine + Placebo at 1.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA80 | Seroconversion at Day 28 | No Seroconversion | 30 Participants |
| Vaccine + Placebo at 1.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA80 | Seroconversion at Day 140 | No Seroconversion | 28 Participants |
| Vaccine at 1.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA80 | Seroconversion at Day 252 | No Seroconversion | 13 Participants |
| Vaccine at 1.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA80 | Seroconversion at Day 196 | No Seroconversion | 7 Participants |
| Vaccine at 1.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA80 | Seroconversion at Day 252 | Seroconversion | 13 Participants |
| Vaccine at 1.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA80 | Seroconversion at Day 56 | Seroconversion | 6 Participants |
| Vaccine at 1.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA80 | Seroconversion at Day 365 | Seroconversion | 9 Participants |
| Vaccine at 1.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA80 | Seroconversion at Day 365 | No Seroconversion | 13 Participants |
| Vaccine at 1.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA80 | Seroconversion at Day 56 | No Seroconversion | 24 Participants |
| Vaccine at 1.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA80 | Seroconversion at Day 84 | Seroconversion | 13 Participants |
| Vaccine at 1.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA80 | Seroconversion at Day 28 | Seroconversion | 1 Participants |
| Vaccine at 1.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA80 | Seroconversion at Day 84 | No Seroconversion | 17 Participants |
| Vaccine at 1.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA80 | Seroconversion at Day 140 | Seroconversion | 8 Participants |
| Vaccine at 1.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA80 | Seroconversion at Day 140 | No Seroconversion | 20 Participants |
| Vaccine at 1.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA80 | Seroconversion at Day 168 | Seroconversion | 8 Participants |
| Vaccine at 1.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA80 | Seroconversion at Day 28 | No Seroconversion | 29 Participants |
| Vaccine at 1.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA80 | Seroconversion at Day 168 | No Seroconversion | 19 Participants |
| Vaccine at 1.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA80 | Seroconversion at Day 196 | Seroconversion | 19 Participants |
| Vaccine + Placebo at 2.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA80 | Seroconversion at Day 252 | No Seroconversion | 20 Participants |
| Vaccine + Placebo at 2.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA80 | Seroconversion at Day 56 | Seroconversion | 0 Participants |
| Vaccine + Placebo at 2.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA80 | Seroconversion at Day 168 | No Seroconversion | 26 Participants |
| Vaccine + Placebo at 2.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA80 | Seroconversion at Day 140 | No Seroconversion | 25 Participants |
| Vaccine + Placebo at 2.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA80 | Seroconversion at Day 365 | No Seroconversion | 18 Participants |
| Vaccine + Placebo at 2.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA80 | Seroconversion at Day 365 | Seroconversion | 4 Participants |
| Vaccine + Placebo at 2.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA80 | Seroconversion at Day 28 | No Seroconversion | 30 Participants |
| Vaccine + Placebo at 2.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA80 | Seroconversion at Day 168 | Seroconversion | 3 Participants |
| Vaccine + Placebo at 2.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA80 | Seroconversion at Day 196 | No Seroconversion | 12 Participants |
| Vaccine + Placebo at 2.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA80 | Seroconversion at Day 84 | Seroconversion | 8 Participants |
| Vaccine + Placebo at 2.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA80 | Seroconversion at Day 252 | Seroconversion | 9 Participants |
| Vaccine + Placebo at 2.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA80 | Seroconversion at Day 84 | No Seroconversion | 22 Participants |
| Vaccine + Placebo at 2.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA80 | Seroconversion at Day 28 | Seroconversion | 0 Participants |
| Vaccine + Placebo at 2.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA80 | Seroconversion at Day 56 | No Seroconversion | 30 Participants |
| Vaccine + Placebo at 2.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA80 | Seroconversion at Day 196 | Seroconversion | 17 Participants |
| Vaccine + Placebo at 2.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA80 | Seroconversion at Day 140 | Seroconversion | 4 Participants |
| Vaccine at 2.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA80 | Seroconversion at Day 168 | Seroconversion | 3 Participants |
| Vaccine at 2.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA80 | Seroconversion at Day 365 | Seroconversion | 9 Participants |
| Vaccine at 2.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA80 | Seroconversion at Day 28 | Seroconversion | 2 Participants |
| Vaccine at 2.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA80 | Seroconversion at Day 28 | No Seroconversion | 28 Participants |
| Vaccine at 2.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA80 | Seroconversion at Day 56 | Seroconversion | 1 Participants |
| Vaccine at 2.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA80 | Seroconversion at Day 56 | No Seroconversion | 29 Participants |
| Vaccine at 2.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA80 | Seroconversion at Day 84 | Seroconversion | 9 Participants |
| Vaccine at 2.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA80 | Seroconversion at Day 84 | No Seroconversion | 21 Participants |
| Vaccine at 2.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA80 | Seroconversion at Day 140 | Seroconversion | 5 Participants |
| Vaccine at 2.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA80 | Seroconversion at Day 140 | No Seroconversion | 23 Participants |
| Vaccine at 2.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA80 | Seroconversion at Day 252 | Seroconversion | 10 Participants |
| Vaccine at 2.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA80 | Seroconversion at Day 168 | No Seroconversion | 23 Participants |
| Vaccine at 2.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA80 | Seroconversion at Day 196 | Seroconversion | 16 Participants |
| Vaccine at 2.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA80 | Seroconversion at Day 196 | No Seroconversion | 11 Participants |
| Vaccine at 2.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA80 | Seroconversion at Day 252 | No Seroconversion | 17 Participants |
| Vaccine at 2.0 mg | Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA80 | Seroconversion at Day 365 | No Seroconversion | 11 Participants |
Secondary
Number of Solicited Adverse Events (AEs) in Study Subjects
The nature, frequency, and severity of solicited adverse events (AE) occurring from the time of each injection through 14 days following the procedure. The total number of events counts all solicited adverse events for all subjects. Subjects may have more than one solicited adverse event per body system and preferred term.
Time frame: The time of each injection through 14 days following the procedure
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Vaccine + Placebo at 1.0 mg | Number of Solicited Adverse Events (AEs) in Study Subjects | Moderate | 13 Adverse Events |
| Vaccine + Placebo at 1.0 mg | Number of Solicited Adverse Events (AEs) in Study Subjects | Mild | 131 Adverse Events |
| Vaccine + Placebo at 1.0 mg | Number of Solicited Adverse Events (AEs) in Study Subjects | Severe | 0 Adverse Events |
| Vaccine + Placebo at 1.0 mg | Number of Solicited Adverse Events (AEs) in Study Subjects | Total Number of Events | 144 Adverse Events |
| Vaccine + Placebo at 1.0 mg | Number of Solicited Adverse Events (AEs) in Study Subjects | Life Threatening | 0 Adverse Events |
| Vaccine at 1.0 mg | Number of Solicited Adverse Events (AEs) in Study Subjects | Moderate | 9 Adverse Events |
| Vaccine at 1.0 mg | Number of Solicited Adverse Events (AEs) in Study Subjects | Total Number of Events | 148 Adverse Events |
| Vaccine at 1.0 mg | Number of Solicited Adverse Events (AEs) in Study Subjects | Mild | 136 Adverse Events |
| Vaccine at 1.0 mg | Number of Solicited Adverse Events (AEs) in Study Subjects | Severe | 3 Adverse Events |
| Vaccine at 1.0 mg | Number of Solicited Adverse Events (AEs) in Study Subjects | Life Threatening | 0 Adverse Events |
| Vaccine + Placebo at 2.0 mg | Number of Solicited Adverse Events (AEs) in Study Subjects | Mild | 147 Adverse Events |
| Vaccine + Placebo at 2.0 mg | Number of Solicited Adverse Events (AEs) in Study Subjects | Total Number of Events | 173 Adverse Events |
| Vaccine + Placebo at 2.0 mg | Number of Solicited Adverse Events (AEs) in Study Subjects | Moderate | 25 Adverse Events |
| Vaccine + Placebo at 2.0 mg | Number of Solicited Adverse Events (AEs) in Study Subjects | Life Threatening | 0 Adverse Events |
| Vaccine + Placebo at 2.0 mg | Number of Solicited Adverse Events (AEs) in Study Subjects | Severe | 1 Adverse Events |
| Vaccine at 2.0 mg | Number of Solicited Adverse Events (AEs) in Study Subjects | Severe | 3 Adverse Events |
| Vaccine at 2.0 mg | Number of Solicited Adverse Events (AEs) in Study Subjects | Mild | 155 Adverse Events |
| Vaccine at 2.0 mg | Number of Solicited Adverse Events (AEs) in Study Subjects | Total Number of Events | 182 Adverse Events |
| Vaccine at 2.0 mg | Number of Solicited Adverse Events (AEs) in Study Subjects | Moderate | 24 Adverse Events |
| Vaccine at 2.0 mg | Number of Solicited Adverse Events (AEs) in Study Subjects | Life Threatening | 0 Adverse Events |