- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02116205
Phase 2a Immunogenicity Study of Hantaan/Puumala Virus DNA Vaccine for Prevention of Hemorrhagic Fever
February 10, 2021 updated by: U.S. Army Medical Research and Development Command
A Phase 2a Double-Blind, Dose-optimizing Study to Evaluate the Immunogenicity of Hantaan/Puumala Virus DNA Vaccine Administered to Healthy Adult Volunteers by Electroporation for Prevention of Hemorrhagic Fever With Renal Syndrome
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.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
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.
Study Type
Interventional
Enrollment (Actual)
130
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
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Maryland
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Silver Spring, Maryland, United States, 20910
- Walter Reed Army Institute of Research Clinical Trials Center
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 49 years (Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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
- For corticosteroids, this will mean prednisone, or equivalent, greater than or equal to 0.5 mg/kg/day
- 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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: 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 mixture, composed of pWRG/HTN-M(co) and pWRG/PUU-M(s2)
Other Names:
0.9% sodium chloride
Other Names:
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
Other Names:
|
Experimental: 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 mixture, composed of pWRG/HTN-M(co) and pWRG/PUU-M(s2)
Other Names:
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
Other Names:
|
Experimental: 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 mixture, composed of pWRG/HTN-M(co) and pWRG/PUU-M(s2)
Other Names:
0.9% sodium chloride
Other Names:
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
Other Names:
|
Experimental: 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 mixture, composed of pWRG/HTN-M(co) and pWRG/PUU-M(s2)
Other Names:
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
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA50
Time Frame: 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.
|
Study Days 0 to 365
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Solicited Adverse Events (AEs) in Study Subjects
Time Frame: 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.
|
The time of each injection through 14 days following the procedure
|
Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA80
Time Frame: 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.
|
Study Days 0 to 365
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Collaborators
Investigators
- Principal Investigator: Kristopher Paolino, MD, WRAIR Clinical Trials Center
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
July 9, 2014
Primary Completion (Actual)
December 7, 2016
Study Completion (Actual)
July 1, 2017
Study Registration Dates
First Submitted
April 14, 2014
First Submitted That Met QC Criteria
April 15, 2014
First Posted (Estimate)
April 16, 2014
Study Record Updates
Last Update Posted (Actual)
February 12, 2021
Last Update Submitted That Met QC Criteria
February 10, 2021
Last Verified
February 1, 2021
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- S-14-01
- 2085 (WRAIR)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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