A Phase I, Randomized, Placebo Controlled, Double-Blind, Dose Escalation Trial to Evaluate the Safety and Immunogenicity of an Andes Virus DNA Vaccine for the Prevention of Hantavirus Pulmonary Syndrome Using the PharmaJet Stratis(R) Needle-Free Injection System in Normal Healthy Adults
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- Hantavirus Pulmonary Infection
- Sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)
- Enrollment
- 48
- Locations
- 1
- Primary Endpoint
- Number of Participants Reporting Vaccine-Related Serious Adverse Events (SAEs) From Day 1 Through Day 337
- Status
- Completed
- Last Updated
- 3 years ago
Overview
Brief Summary
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.
Detailed Description
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Provide written informed consent before initiation of any study procedures.
- •Are able to understand and comply with planned study procedures and be available for all study visits/phone calls.
- •Males or non-pregnant females ages 18-49, inclusive.
- •Are in good health\*. \*As determined by medical history and physical examination to evaluate acute or currently ongoing chronic medical diagnoses or conditions, defined as those that have been present for at least 90 days which would affect the assessment of the safety of subjects or the immunogenicity of study vaccinations. Chronic medical diagnoses or conditions should be stable for the last 60 days (no hospitalizations, ER or urgent care for condition and no adverse symptoms that need medical intervention such as medication change/supplemental oxygen). This includes no change in chronic prescription medication, dose, or frequency as a result of deterioration of the chronic medical diagnosis or condition in the 60 days prior to enrollment. Any prescription change that is due to change of health care provider, insurance company, etc., or that is done for financial reasons, as long as in the same class of medication, will not be considered a deviation of this inclusion criterion. Any change in prescription medication due to improvement of a disease outcome, as determined by the site principal investigator or appropriate sub-investigator, will not be considered a deviation of this inclusion criterion. Subjects may be on chronic or as needed (prn) medications if, in the opinion of the site principal investigator or appropriate sub-investigator, they pose no additional risk to subject safety or assessment of reactogenicity and immunogenicity and do not indicate a worsening of medical diagnosis or condition. Similarly, medication changes subsequent to enrollment and study vaccination are acceptable provided there was no deterioration in the subject's chronic medical condition that necessitated a medication change, and there is no additional risk to the subject or interference with the evaluation of responses to study vaccination. Note: Topical, nasal, and inhaled medications (apart from steroids as outlined in the Subject Exclusion Criteria), herbals, vitamins, and supplements are permitted.
- •Oral temperature is less than 100.0 degrees Fahrenheit (37.8 degrees Celsius).
- •Pulse is 47 to 105 beats per minute (bpm), inclusive.
- •Systolic blood pressure (BP) is 85 to 150 mm Hg, inclusive.
- •Diastolic blood pressure (BP) is 55 to 95 mm Hg, inclusive.
- •Have acceptable screening laboratories\* within 28 days prior to enrollment. \*Screening laboratory values that are outside acceptable range but are thought to be due to an acute condition or due to laboratory error may be repeated once.
- •Urine protein screen is negative or trace.
Exclusion Criteria
- •Women who are pregnant, planning to become pregnant or lactating\*. \*Includes breastfeeding or planning to breastfeed at any given time from the receipt of study vaccination through the 12-month trial period.
- •Known allergy or history of anaphylaxis, severe local or other serious adverse reactions to vaccines or vaccine products\*, or history of severe allergic reactions.
- •\*This includes a known allergy to an aminoglycoside (e.g., gentamicin, tobramycin, neomycin, streptomycin).
- •Received an experimental agent\* within 3 months prior to study vaccination, or expects to receive an experimental agent\*\* during the 12-month trial-reporting period.
- •\*Including vaccine, drug, biologic, device, blood product, or medication.
- •\*\*Other than from participation in this study.
- •Received any licensed live vaccine within 28 days prior to or after each study vaccination.
- •Received a licensed inactivated vaccine within 14 days prior to or after each study vaccination\*.
- •\*Allowable exception for inactivated seasonal influenza vaccine received more than 7 days prior to or after a study vaccination.
- •Individuals in whom the ability to observe possible local reactions at the eligible injection sites (deltoid region) is, unacceptably obscured due to a physical condition or permanent body art.
Outcomes
Primary Outcomes
Number of Participants Reporting Vaccine-Related Serious Adverse Events (SAEs) From Day 1 Through Day 337
Time Frame: 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.
Number of Participants Experiencing Clinical Safety Laboratory Adverse Events
Time Frame: Day 8, Day 36, Day 64, Day 176
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).
Number of Participants Reporting Solicited Local Adverse Events From Day 57 Through Day 64
Time Frame: 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.
Number of Participants Reporting Solicited Systemic Adverse Events From Day 29 Through Day 36
Time Frame: 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.
Number of Participants Reporting Serious Adverse Events (SAEs) From Day 1 Through Day 337
Time Frame: 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.
Number of Participants Reporting Solicited Systemic Adverse Events From Day 169 Through Day 176
Time Frame: 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.
Number of Participants Experiencing Unsolicited Non-Serious Adverse Events at Any Time From Day 1 to Day 197
Time Frame: Day 1 through 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.
Number of Participants Experiencing Vaccine-Related Unsolicited Non-Serious Adverse Events at Any Time From Day 1 to Day 197
Time Frame: Day 1 through 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.
Number of Participants Reporting Solicited Local Adverse Events From Day 1 Through Day 8
Time Frame: 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.
Number of Participants Reporting Solicited Local Adverse Events From Day 29 Through Day 36
Time Frame: 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.
Number of Participants Reporting Solicited Systemic Adverse Events From Day 57 Through Day 64
Time Frame: 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.
Number of Participants Reporting Solicited Local Adverse Events From Day 169 Through Day 176
Time Frame: 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.
Number of Participants Reporting Solicited Systemic Adverse Events From Day 1 Through Day 8
Time Frame: 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.
Secondary Outcomes
- Number of Participants With ANDV Antibody Titers Greater Than or Equal to 20 as Measured by Plaque Reduction Neutralization Titers(Day 57, Day 85, Day 197)
- Percentage of Participants Achieving ANDV Antibody Seroconversion as Measured by Plaque Reduction Neutralization Titers(Day 57, Day 85, Day 197)
- Percentage of Participants Achieving ANDV Antibody Seroconversion at Day 57 as Measured by Pseudovirion Neutralization Titers(Day 57, Day 85, Day 197)
- Geometric Mean Titers (GMTs) of Neutralizing Antibodies to ANDV Measured by Plaque Reduction Neutralization Titers(Day 1, Day 57, Day 85, Day 197)
- Geometric Mean Titers (GMTs) of Neutralizing Antibodies to ANDV Measured by Pseudovirion Neutralization Titers(Day 1, 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(Day 57, Day 85, Day 197)