This is a Phase 1, randomized, placebo controlled, double-blind, dose escalation trial of 48 males and non-pregnant females, 18-49 years old, inclusive, who are in good health and meet all eligibility criteria. This trial is designed to assess the safety, reactogenicity and immunogenicity of an Andes Virus (ANDV) DNA vaccine for the prevention of Hantavirus Pulmonary Syndrome (HPS). ANDV DNA vaccine or placebo will be administered using the PharmaJet Stratis(R) Needle-Free Injection System. The study duration is 23 months while the subject participation duration is 12 months. Subjects assigned to the 3 dose regimen will receive ANDV DNA vaccine on Days 1, 29 and 169, and placebo on Day 57. Subjects assigned to the 4 dose regimen will receive ANDV DNA on Days 1, 29, 57 and 169. Two doses (2 or 4 mg) of ANDV DNA vaccine will be evaluated. The primary objective of this study is to assess the safety and reactogenicity of the ANDV DNA vaccine by dosage cohort and treatment arm when administered using the PharmaJet Stratis(R) Needle-Free Injection system in normal, healthy adults.
This is a Phase 1, randomized, placebo controlled, double-blind, dose escalation trial of 48 males and non-pregnant females, 18-49 years old, inclusive, who are in good health and meet all eligibility criteria. This trial is designed to assess the safety, reactogenicity and immunogenicity of an Andes Virus (ANDV) DNA vaccine for the prevention of Hantavirus Pulmonary Syndrome (HPS). ANDV DNA vaccine or placebo will be administered using the PharmaJet Stratis(R) Needle-Free Injection System. The study duration is 23 months while the subject participation duration is 12 months. Subjects assigned to the 3 dose regimen will receive ANDV DNA vaccine on Days 1, 29 and 169, and placebo on Day 57. Subjects assigned to the 4 dose regimen will receive ANDV DNA on Days 1, 29, 57 and 169. Two doses (2 or 4 mg) of ANDV DNA vaccine will be evaluated. The primary objective of this study is to assess the safety and reactogenicity of the ANDV DNA vaccine by dosage cohort and treatment arm when administered using the PharmaJet Stratis(R) Needle-Free Injection system in normal, healthy adults. The secondary objective of this study is to assess the immunogenicity of the ANDV DNA vaccine by dosage cohort and treatment arm.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
DOUBLE
Enrollment
48
A vaccine targeting the hantavirus pulmonary syndrome (HPS) causative agent Andes Virus (ANDV), with potential pan-hantavirus effect. The plasmid backbone, pWRG7077, is modified to produce the active ingredient of the vaccine, plasmid pWRG/AND-M (opt2), and includes the ANDV M gene responsible for encoding viral GnGc envelope glycoproteins. ANDV DNA vaccine will be administered intramuscularly at 2 mg or 4 mg doses using the PharmaJet Stratis Needle-Free Injection System.
Normal saline injections will be administered intramuscularly as matching placebo using the PharmaJet Stratis Needle-Free Injection System
Cincinnati Children's Hospital Medical Center - Infectious Diseases
Cincinnati, Ohio, United States
Number of Participants Experiencing Clinical Safety Laboratory Adverse Events
Laboratory parameters include alanine aminotransferase (ALT), total bilirubin, creatinine, blood urea nitrogen (BUN), hemoglobin, absolute neutrophil count (ANC), sodium, potassium, white blood cells (WBC), and platelet count. Laboratory results were considered adverse events using the following thresholds: ALT 50 IU/L or greater; total bilirubin 1.30 mg/dL or greater; creatinine 0.81 mg/dL or greater (female) or 1.11 mg/dL or greater (male); BUN 24 mg/dL or greater; hemoglobin 11.6 g/dL or lower (female) or 13.2 g/dL or lower (male); ANC \<1.8 K/mcL; sodium 135 mmol/L or lower (decrease) or 146 mmol/L or greater (increase); potassium 3.0 mmol/L or lower (decrease) or 5.2 mmol/L or greater (increase); WBC 4.4 K/mcL or lower (decrease) or 13.1 K/mcL or greater (increase 18 to \<21 years) and 11.1 K/mcL or greater (increase 21 years or older); or platelets 134 K/mcL or below (decrease) or 467 K/mcL or greater (increase).
Time frame: Day 8, Day 36, Day 64, Day 176
Number of Participants Reporting Serious Adverse Events (SAEs) From Day 1 Through Day 337
An adverse event was considered serious if it resulted in any of the following outcomes: death, a life-threatening adverse event (its occurrence places the participant at immediate risk of death), inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or a congenital anomaly/birth defect. Adverse events can be considered serious when they may jeopardize the patient or participant and may require medical or surgical intervention to prevent one of the outcomes listed in this definition.
Time frame: Day 1 through Day 337
Number of Participants Reporting Vaccine-Related Serious Adverse Events (SAEs) From Day 1 Through Day 337
An adverse event is considered serious if it results in any of the following outcomes: death, a life-threatening adverse event (its occurrence places the participant at immediate risk of death), inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or a congenital anomaly/birth defect. Adverse events can be considered serious when they may jeopardize the patient or participant and may require medical or surgical intervention to prevent one of the outcomes listed in this definition. An adverse event was considered related to the study product if there was a reasonable possibility that the study product caused the adverse event. Reasonable possibility means that there is evidence to suggest a causal relationship between the study product and the adverse event.
Time frame: Day 1 through Day 337
Number of Participants Experiencing Unsolicited Non-Serious Adverse Events at Any Time From Day 1 to Day 197
Adverse events were defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product regardless of its causal relationship to the study treatment. Unsolicited non-serious AEs were documented and reported from the time of first study vaccination through 28 days after the last study vaccination or after Day 169 if the fourth vaccination wasn't received.
Time frame: Day 1 through Day 197
Number of Participants Experiencing Vaccine-Related Unsolicited Non-Serious Adverse Events at Any Time From Day 1 to Day 197
Adverse events were defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product regardless of its causal relationship to the study treatment. Unsolicited non-serious AEs were documented and reported from the time of first study vaccination through 28 days after the last study vaccination or after Day 169 if the fourth vaccination wasn't received. An adverse event was considered related to the study product if there was a reasonable possibility that the study product caused the adverse event. Reasonable possibility means that there is evidence to suggest a causal relationship between the study product and the adverse event.
Time frame: Day 1 through Day 197
Number of Participants Reporting Solicited Local Adverse Events From Day 1 Through Day 8
Local adverse events solicited on a memory aid provided to participants included pain, tenderness, erythema, erythema measurement (measuring \>0mm), induration, induration measurement (measuring \>0mm), skin discoloration, ecchymosis, and ecchymosis measurement (measuring \>0mm). Participants were considered to have experienced the AE if they reported an event of mild or greater severity on any of the 7 days following the first vaccination.
Time frame: Day 1 through Day 8
Number of Participants Reporting Solicited Local Adverse Events From Day 29 Through Day 36
Local adverse events solicited on a memory aid provided to participants included pain, tenderness, erythema, erythema measurement (measuring \>0mm), induration, induration measurement (measuring \>0mm), skin discoloration, ecchymosis, and ecchymosis measurement (measuring \>0mm). Participants were considered to have experienced the AE if they reported an event of mild or greater severity on any of the 7 days following the second vaccination.
Time frame: Day 29 through Day 36
Number of Participants Reporting Solicited Local Adverse Events From Day 57 Through Day 64
Local adverse events solicited on a memory aid provided to participants included pain, tenderness, erythema, erythema measurement (measuring \>0mm), induration, induration measurement (measuring \>0mm), skin discoloration, ecchymosis, and ecchymosis measurement (measuring \>0mm). Participants were considered to have experienced the AE if they reported an event of mild or greater severity on any of the 7 days following the third vaccination.
Time frame: Day 57 through Day 64
Number of Participants Reporting Solicited Local Adverse Events From Day 169 Through Day 176
Local adverse events solicited on a memory aid provided to participants included pain, tenderness, erythema, erythema measurement, induration, induration measurement, skin discoloration, ecchymosis, and ecchymosis measurement. Participants were considered to have experienced the AE if they reported an event of mild or greater severity on any of the 7 days following the fourth vaccination.
Time frame: Day 169 through Day 176
Number of Participants Reporting Solicited Systemic Adverse Events From Day 1 Through Day 8
Systemic adverse events solicited on a memory aid provided to participants included feverishness, malaise, fatigue, myalgia, headache, nausea, dizziness, and fever. Participants were considered to have experienced the AE if they reported an event of mild or greater severity on any of the 7 days following the first vaccination.
Time frame: Day 1 through Day 8
Number of Participants Reporting Solicited Systemic Adverse Events From Day 29 Through Day 36
Systemic adverse events solicited on a memory aid provided to participants included feverishness, malaise, fatigue, myalgia, headache, nausea, dizziness, and fever. Participants were considered to have experienced the AE if they reported an event of mild or greater severity on any of the 7 days following the second vaccination.
Time frame: Day 29 through Day 36
Number of Participants Reporting Solicited Systemic Adverse Events From Day 57 Through Day 64
Systemic adverse events solicited on a memory aid provided to participants included feverishness, malaise, fatigue, myalgia, headache, nausea, dizziness, and fever. Participants were considered to have experienced the AE if they reported an event of mild or greater severity on any of the 7 days following the third vaccination.
Time frame: Day 57 through Day 64
Number of Participants Reporting Solicited Systemic Adverse Events From Day 169 Through Day 176
Systemic adverse events solicited on a memory aid provided to participants included feverishness, malaise, fatigue, myalgia, headache, nausea, dizziness, and fever. Participants were considered to have experienced the AE if they reported an event of mild or greater severity on any of the 7 days following the fourth vaccination. Systemic AEs were considered mild severity if they were noticeable but did not interfere with daily activity; events (other than headache) were considered moderate severity if they interfered with daily activity; events (other than headache) were considered severe severity if they caused significant interference and prevented daily activity. Headache events were considered moderate severity if they required any use of pain reliever or interfered with daily activity; headache events were severe if they prevented daily activity or required use of a prescription medication.
Time frame: Day 169 through Day 176
Geometric Mean Titers (GMTs) of Neutralizing Antibodies to ANDV Measured by Plaque Reduction Neutralization Titers
Venous blood was collected to perform a 50% plaque reduction neutralization test (PRNT) which was conducted with Andes Virus as the antigen. The geometric mean titer was calculated for each study arm from the results available at Day 1 prior to the first study vaccination, 28 days following the second study vaccination (and immediately prior to the third study vaccination; Day 57), 28 days following the third study vaccination (Day 85), and 28 days following the fourth study vaccination (Day 197). Results lower than the limit of detection (\<20) were reported and analyzed as 14.1 (which is 20/ sqrt(2)).
Time frame: Day 1, Day 57, Day 85, Day 197
Geometric Mean Titers (GMTs) of Neutralizing Antibodies to ANDV Measured by Pseudovirion Neutralization Titers
Venous blood was collected to perform a 50% pseudovirion neutralization assay (PsVNA) which was conducted with Andes Virus as the antigen. The geometric mean titer was calculated for each study arm from the results available at Day 1 prior to the first study vaccination, 28 days following the second study vaccination (and immediately prior to the third study vaccination; Day 57), 28 days following the third study vaccination (Day 85), and 28 days following the fourth study vaccination (Day 197). Results lower than the limit of detection (\<20) were reported and analyzed as 14.1 (which is 20/ sqrt(2)).
Time frame: Day 1, Day 57, Day 85, Day 197
Number of Participants With ANDV Antibody Titers Greater Than or Equal to 20 as Measured by Plaque Reduction Neutralization Titers
Venous blood was collected to perform a 50% plaque reduction neutralization test (PRNT) which was conducted with Andes Virus as the antigen. The number of participants with a titer greater than or equal to 20 was recorded for each study arm from the results available at 28 days following the second study vaccination (and immediately prior to the third study vaccination; Day 57), 28 days following the third study vaccination (Day 85), and 28 days following the fourth study vaccination (Day 197).
Time frame: Day 57, Day 85, Day 197
Number of Participants With ANDV Antibody Titers Greater Than or Equal to 20 as Measured by Pseudovirion Neutralization Titers
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Venous blood was collected to perform a 50% pseudovirion neutralization assay (PsVNA) which was conducted with Andes Virus as the antigen. The number of participants with a titer greater than or equal to 20 was recorded for each study arm from the results available at 28 days following the second study vaccination (and immediately prior to the third study vaccination; Day 57), 28 days following the third study vaccination (Day 85), 28 days following the fourth study vaccination (Day 197).
Time frame: Day 57, Day 85, Day 197
Percentage of Participants Achieving ANDV Antibody Seroconversion as Measured by Plaque Reduction Neutralization Titers
Venous blood was collected to perform a 50% plaque reduction neutralization test (PRNT) which was conducted with Andes Virus as the antigen. A participant was considered to have seroconverted if their titer measured at least 40 if the baseline titer was less than 20, or if there was at least a 4-fold rise in titers from baseline if the baseline titer was greater than or equal to 20. The number of participants seroconverting was recorded for each study arm from the results at 28 days following the second study vaccination (and immediately prior to the third study vaccination; Day 57), 28 days following the third study vaccination (Day 85), and 28 days following the fourth study vaccination (Day 197).
Time frame: Day 57, Day 85, Day 197
Percentage of Participants Achieving ANDV Antibody Seroconversion at Day 57 as Measured by Pseudovirion Neutralization Titers
Venous blood was collected to perform a 50% pseudovirion neutralization assay (PsVNA) which was conducted with Andes Virus as the antigen. A participant was considered to have seroconverted if their titer measured at least 40 if the baseline titer was less than 20, or if there was at least a 4-fold rise in titers from baseline if the baseline titer was greater than or equal to 20. The number of participants seroconverting was recorded for each study arm from the results at 28 days following the second study vaccination (and immediately prior to the third study vaccination; Day 57), 28 days following the third study vaccination (Day 85), and 28 days following the fourth study vaccination (Day 197).
Time frame: Day 57, Day 85, Day 197