Hemorrhagic Fever With Renal SyndromePhase 2NCT02116205
Phase 2a Immunogenicity Study of Hantaan/Puumala Virus DNA Vaccine for Prevention of Hemorrhagic Fever
A Phase 2 study testing HTNV/PUUV DNA vaccine and TriGrid Delivery System (TDS) in people with Hemorrhagic Fever With Renal Syndrome, run by U.S. Army Medical Research and Development Command at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 49 yearsHealthy volunteers can take part
- Conditions the study is for
- Hemorrhagic Fever With Renal Syndrome
- What is being tested?
- HTNV/PUUV DNA vaccine and TriGrid Delivery System (TDS)
- Type of treatment
- Vaccines, Injection or infusion, Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 130 participants
- Where
- 1 siteUnited States
- Study dates
- 9 Jul 2014to Jul 2017
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 49 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 19Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Walter Reed Army Institute of Research Clinical Trials Center
Silver Spring, Maryland, 20910
About this study
Official title: 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.
Read the 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.
- Conditions
- Hemorrhagic Fever With Renal Syndrome
- Being tested
- HTNV/PUUV DNA vaccine, Placebo, TriGrid Delivery System (TDS)
- Keywords
- Hantaan virus, Puumala virus, HFRS
- Medical subject headings
- Hemorrhagic Fever with Renal Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HTNV/PUUV DNA vaccineBiological
Also called Hantaan Virus/Puumala Virus DNA Vaccine
HTNV/PUUV DNA vaccine mixture, composed of pWRG/HTN-M(co) and pWRG/PUU-M(s2)
PlaceboBiological
Also called Normal saline placebo
0.9% sodium chloride
TriGrid Delivery System (TDS)Device
Also called TriGrid Delivery System for intramuscular delivery (TDS-IM)
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
| Study group | Role | What they receive |
|---|---|---|
| Vaccine + Placebo at 1.0 mg | Experimental | 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. Receives: Biological: HTNV/PUUV DNA vaccine; Biological: Placebo; Device: TriGrid Delivery System (TDS) |
| Vaccine at 1.0 mg | Experimental | 1.0 mg HTNV/PUUV DNA vaccine IM-EP via TriGrid™ Delivery System (TDS) on Study Day 0, 28, 56 and 168. Receives: Biological: HTNV/PUUV DNA vaccine; Device: TriGrid Delivery System (TDS) |
| Vaccine + Placebo at 2.0 mg | Experimental | 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. Receives: Biological: HTNV/PUUV DNA vaccine; Biological: Placebo; Device: TriGrid Delivery System (TDS) |
| Vaccine at 2.0 mg | Experimental | 2.0 mg HTNV/PUUV DNA vaccine IM-EP via TriGrid™ Delivery System (TDS) on Study Day 0, 28, 56 and 168. Receives: Biological: HTNV/PUUV DNA vaccine; Device: TriGrid Delivery System (TDS) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Study Days 0 to 365
Secondary outcomes (2)
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.
Measured: The time of each injection through 14 days following the procedure
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.
Measured: Study Days 0 to 365
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Apr 2014 (estimated)
- Study start9 Jul 2014
- Primary completion7 Dec 2016
- Study completionJul 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Hemorrhagic Fever With Renal SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 130 participants (actual)
Sponsor and investigators
- Lead sponsor
- U.S. Army Medical Research and Development Command
- Sponsor type
- US federal agency
- Collaborators
- 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
- Responsible party
- Sponsor
- Investigators
- Kristopher Paolino, MD, Principal investigator, WRAIR Clinical Trials Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02116205
- Sponsor's protocol ID
- S-14-01
- Other IDs
- 2085
- Status last verified
- Feb 2021
- First submitted
- 14 Apr 2014
- Last updated
- 12 Feb 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT02116205
- Acronym / sponsor ID
- S-14-01
- Conditions
- Hemorrhagic Fever With Renal Syndrome
- Keywords
- Hantaan virus, Puumala virus, HFRS
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 130 participants (actual)
- Lead sponsor
- U.S. Army Medical Research and Development CommandUS federal agency
- Collaborators
- 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
- Study start
- 9 Jul 2014 (actual)
- Primary completion
- 7 Dec 2016 (actual)
- Study completion
- Jul 2017 (actual)
- First posted
- 16 Apr 2014 (estimated)
- Results
- Posted 1 Dec 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Vaccine + Placebo at 1.0 mg | Experimental | Biological: HTNV/PUUV DNA vaccine, Biological: Placebo, Device: TriGrid Delivery System (TDS)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. |
| Vaccine at 1.0 mg | Experimental | Biological: HTNV/PUUV DNA vaccine, Device: TriGrid Delivery System (TDS)1.0 mg HTNV/PUUV DNA vaccine IM-EP via TriGrid™ Delivery System (TDS) on Study Day 0, 28, 56 and 168. |
| Vaccine + Placebo at 2.0 mg | Experimental | Biological: HTNV/PUUV DNA vaccine, Biological: Placebo, Device: TriGrid Delivery System (TDS)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. |
| Vaccine at 2.0 mg | Experimental | Biological: HTNV/PUUV DNA vaccine, Device: TriGrid Delivery System (TDS)2.0 mg HTNV/PUUV DNA vaccine IM-EP via TriGrid™ Delivery System (TDS) on Study Day 0, 28, 56 and 168. |
Who may qualify
- Ages
- 18 to 49 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (19 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| HTNV/PUUV DNA vaccineAlso: Hantaan Virus/Puumala Virus DNA VaccineHTNV/PUUV DNA vaccine mixture, composed of pWRG/HTN-M(co) and pWRG/PUU-M(s2) | Biological | Vaccine + Placebo at 1.0 mg, Vaccine + Placebo at 2.0 mg, Vaccine at 1.0 mg, Vaccine at 2.0 mg |
| PlaceboAlso: Normal saline placebo0.9% sodium chloride | Biological | Vaccine + Placebo at 1.0 mg, Vaccine + Placebo at 2.0 mg |
| TriGrid Delivery System (TDS)Also: TriGrid Delivery System for intramuscular delivery (TDS-IM)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 | Device | Vaccine + Placebo at 1.0 mg, Vaccine + Placebo at 2.0 mg, Vaccine at 1.0 mg, Vaccine at 2.0 mg |
Primary outcome
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.
2 secondary outcomes
Number of Solicited Adverse Events (AEs) in Study Subjects
Time frame: 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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Feb 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kristopher Paolino, MD principal investigator
WRAIR Clinical Trials Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing HTNV/PUUV DNA vaccine and TriGrid Delivery System (TDS) in people with Hemorrhagic Fever With Renal Syndrome, run by U.S. Army Medical Research and Development Command at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 1 Dec 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA50 (time frame: Study Days 0 to 365). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Feb 2021.