Safety and Immunogenicity of a Hantaan Virus DNA Vaccine and a Puumala Virus DNA Vaccine, For The Prevention of Hemorrhagic Fever With Renal Syndrome

NCT ID: NCT04333459

Last Updated: 2022-02-18

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE2

Total Enrollment

132 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-08-23

Study Completion Date

2023-12-31

Brief Summary

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A randomized 4 cohort study that is comparing the data collected during the earlier phase study and to determine if immunogenicity can be retained with a 1 mg dose of Hantaan DNA vaccine.

Detailed Description

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The study will enroll 4 randomized groups of 33 subjects each for a total of 132 subjects. Every subject will receive a total of 4 vaccinations. Subjects and study personnel will be blinded to the group that they are randomized to (double-blind). The study is intended to substantiate the Phase 1 results with the 2 mg dose and to also determine if immunogenicity can be retained with a 1 mg dose (for HTNV DNA vaccine).

For the 2 mg dose, each vaccination consists of 2 administrations of 1 mg (left and right deltoid) for a total of 2 mg/vaccination. For the 1 mg dose, each vaccination consists of 2 administrations of 0.5 mg (left and right deltoid) for a total of 1 mg/vaccination.

Group 1 will be vaccinated with the HTNV DNA vaccine, pWRG/HTN-M(co) at the 2 mg/vaccination dose. Group 2 will be vaccinated with the HTNV DNA vaccine, pWRG/HTN-M(co) at the 1 mg/vaccination dose. Group 3 will be vaccinated with the PUUV DNA vaccine, pWRG/PUU-M(s2) at the 2 mg/vaccination dose. Group 4 will be vaccinated with the PUUV DNA vaccine, pWRG/PUU-M(s2) at the 1 mg/vaccination dose. Each group will be vaccinated on Days 1, 29, 57 and 169. All doses will be administered with the PharmaJet Stratis device, which is FDA cleared for IM administration of vaccines. All subjects will be followed until 1 month after the last vaccination with Day 197 being the final study visit. Subjects will complete post-injection memory aids for 7 days after each vaccination.

Conditions

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Hantaan Virus Nephropathy Puumala Virus Nephropathy

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

DIAGNOSTIC

Blinding Strategy

DOUBLE

Participants Investigators
Double-blind Study

Study Groups

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Group 1 - Full Dose Hataan

Group 1 will be vaccinated with the "Full Dose" of HTNV DNA vaccine, 2 mg of pWRG/HTN-M(co) with 0.5 mg/each deltoid.

Group Type ACTIVE_COMPARATOR

Hataan DNA Vaccine/Puumala DNA Vaccine

Intervention Type BIOLOGICAL

Vaccine compared in High and Lose Doses.

Group 2 - Half Dose Hataan

Group 2 will be vaccinated with the "Half Dose" of HTNV DNA vaccine, 1 mg of pWRG/HTN-M(co) with 1.0 mg/each deltoid.

Group Type ACTIVE_COMPARATOR

Hataan DNA Vaccine/Puumala DNA Vaccine

Intervention Type BIOLOGICAL

Vaccine compared in High and Lose Doses.

Group 3 - Full Dose Puumala

Group 3 will be vaccinated with the "Full Dose" of PUUV DNA vaccine, 2 mg of pWRG/PUU-M(s2) with 1.0 mg/each deltoid.

Group Type ACTIVE_COMPARATOR

Hataan DNA Vaccine/Puumala DNA Vaccine

Intervention Type BIOLOGICAL

Vaccine compared in High and Lose Doses.

Group 4 - Half Dose Puumala

Group 4 will be vaccinated with the "Half Dose" of PUUV DNA vaccine, 1 mg of pWRG/PUU-M(s2) with 1.0 mg/each deltoid.

Group Type ACTIVE_COMPARATOR

Hataan DNA Vaccine/Puumala DNA Vaccine

Intervention Type BIOLOGICAL

Vaccine compared in High and Lose Doses.

Interventions

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Hataan DNA Vaccine/Puumala DNA Vaccine

Vaccine compared in High and Lose Doses.

Intervention Type BIOLOGICAL

Eligibility Criteria

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Inclusion Criteria

Subjects must meet all of the following criteria to be included in the study:

1. Healthy adult male or nonpregnant, nonlactating female, ages 18-49 (inclusive) at the time of screening
2. Have provided written informed consent before screening
3. Completion of Study Comprehension Quiz (minimum passing score of 80% with 2 attempts permitted).
4. A subject must have a valid state or government-issued photo ID (eg, driver's license, military ID, or U.S. passport) \& be able to pass a background check in order to gain access to the base \& participate.
5. Free of clinically significant health problems, as determined by pertinent medical history and clinical examination with ECG and laboratory assessments prior to entry into the study
6. Available and able to participate for all study visits and procedures
7. Females subjects must have had a hysterectomy or bilateral oopherectomy or must be using an effective method of contraception\*\* from 30 days prior to the first study vaccination until 90 days after the last study vaccination.

\*\* For this study, we define an effective contraceptive method as one that results in a failure rate of less than 1% per year when it is used consistently and correctly. This includes, but is not limited to, abstinence from sexual intercourse with a male partner, monogamous relationship with a vasectomized partner, bilateral tubal ligation, or intrauterine devices.
8. Female subjects who have not had a hysterectomy or bilateral oopherectomy must have a negative serum pregnancy test at screening and a negative urine pregnancy test within 24 hours prior to each study vaccination.
9. Sexually active male participants whose partner is a woman who has not had a hysterectomy or bilateral oopherectomy and has not had a vasectomy\*\* must agree not to father a child until 90 days after the last vaccination.

\*\* performed \> 1 year prior to screening
10. Women agree to not donate eggs (ova, oocytes) and male subject agrees not to donate sperm from the start of screening onwards until at least 90 days after the last vaccination.
11. Agree not to participate in another clinical trial during the study period.
12. Agree not to donate blood to a blood bank for 3 months after receiving the last study vaccine.
13. Have acceptable screening laboratories\* within 90 days prior to enrollment. Refer to Appendix A for range of acceptable laboratory values. 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. \[see Manual of Procedures (MOP)\]
14. Negative HIV testing (HIV Ab / antigen 4th generation screen with reflex confirmatory RNA testing).
15. Negative hepatitis B surface antigen (HBsAg) and hepatitis C antibody testing.

Exclusion Criteria

Subjects meeting any of the following criteria will be excluded from the study:

1. History of previous hantavirus vaccine.
2. History of severe local or systemic reactions to any vaccination or a history of severe allergic reactions
3. Ongoing participation in another clinical trial (those continuing through Day 197 will not join other new studies until their final visit)
4. Receipt of licensed vaccines within 7 days before or after immunization (30 days for live vaccines)
5. Any use of investigational drugs or vaccines within 30 days before starting the study.
6. Ability to observe possible local reactions at the eligible injection sites (deltoid region) is, in the opinion of the investigator, unacceptably obscured due to a physical condition or permanent body art
7. 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, and/or laboratory screening test
8. Pregnant or lactating female, or female who intends to become pregnant during the study period
9. Administration of immunoglobulins and/or any blood products within the 120 days preceding study entry or planned administration during the study period
10. Blood donation for human use (eg, American Red Cross or other similar blood drives) within the 56 days preceding study entry or planned administration during the study period
11. Any confirmed evidence of hepatitis B or C infection
12. Have an acute illness\*, as determined by the site PI or appropriate sub-investigator, within 72 hours prior to study vaccination.

\*An acute illness which is nearly resolved with only minor residual symptoms remaining is allowable if, in the opinion of the site PI or appropriate sub-investigator, the residual symptoms will not interfere with the ability to assess safety parameters as required by the protocol. Subjects may re-screen after an acute illness is resolved
13. Any confirmed or suspected immunosuppressive or immunodeficient condition or use of anticancer chemotherapy or radiation therapy (cytotoxic) within 3 years prior to study vaccination.
14. 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, inhaled, and topical steroids are allowed (daily inhaled steroids for treatment of asthma are NOT allowed)
15. Any chronic or active neurologic disorder, including seizures and epilepsy, excluding a single febrile seizure as a child and intermittent non migraine headaches
16. Have any diagnosis, current or past, of schizophrenia, bipolar disease, or other psychiatric diagnosis that may interfere with subject compliance or safety evaluations.
17. Have any plan to have surgery between enrollment and the end of the study.
18. Have been hospitalized for psychiatric illness, history of suicide attempt, or confinement for danger to self or others within 10 years prior to study vaccination.
19. Have received any antiviral within 3 days of study vaccination.
20. A diagnosis of Type I or II diabetes.
21. Suspected or known current alcohol or drug abuse. Alcohol abuse defined by an alcohol intake of greater than 3 drinks a day on average for a man, and greater than 2 drinks a day on average for a woman.
22. Unwilling to allow storage and use of blood for future hantavirus-related research
23. 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
Minimum Eligible Age

18 Years

Maximum Eligible Age

49 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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U.S. Army Medical Research and Development Command

FED

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Clinical Trials Center, Walter Reed Army Institute of Reserach

Silver Spring, Maryland, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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James N Moon, MD

Role: CONTACT

301-922-7230

Michael Koren, MD

Role: CONTACT

301-319-9904

Facility Contacts

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James Moon, MD

Role: primary

301-319-9176

Other Identifiers

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S-19-06

Identifier Type: -

Identifier Source: org_study_id

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