Andes Virus DNA Vaccine for the Prevention of Hantavirus Pulmonary Syndrome Using the PharmaJet Stratis(R) Needle-Free Injection Delivery Device

NCT ID: NCT03682107

Last Updated: 2022-11-22

Study Results

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Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

48 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-02-19

Study Completion Date

2020-09-23

Brief Summary

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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

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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.

Conditions

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Hantavirus Pulmonary Infection Immunisation

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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Arm 1 (2 mg ANDV - 3-dose regimen)

1 sentinel subject assigned to the 3-dose regimen will receive 2 mg (2 injections of 0.5 ml (1 mg/0.5 ml each)) of ANDV DNA vaccine intramuscularly into the left and right deltoid on Day 1 in an open label manner, and 2 mg (2 injections of 0.5 ml (1 mg/0.5 ml each)) of ANDV DNA vaccine on Days 29, 169, and matching placebo on Day 57 in double-blind manner.

11 subjects assigned to the 3-dose regimen will receive either 2 mg (2 injections of 0.5 ml (1 mg/0.5 ml each)) of ANDV DNA vaccine intramuscularly into the left and right deltoid on Days 1, 29, 169, and matching placebo on Day 57 (n=9) or matching placebo on Days 1, 29, 57, and 169 (n=2).

Group Type EXPERIMENTAL

Andes virus DNA vaccine

Intervention Type BIOLOGICAL

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.

Placebo

Intervention Type OTHER

Normal saline injections will be administered intramuscularly as matching placebo using the PharmaJet Stratis Needle-Free Injection System

Arm 2 (2 mg ANDV - 4-dose regimen)

1 sentinel subject assigned to the 4-dose regimen will receive 2 mg (2 injections of 0.5 ml (1 mg/0.5 ml each)) of ANDV DNA vaccine intramuscularly into the left and right deltoid on Day 1 in an open label manner, and Days 29, 57 and 169 in double-blind manner.

11 subjects assigned to the 4-dose regimen will receive either 2 mg (2 injections of 0.5 ml (1 mg/0.5 ml each)) of ANDV DNA vaccine intramuscularly into the left and right deltoid on Days 1, 29, 57 and 169 (n=9) or matching placebo on Days 1, 29, 57, and 169 (n=2).

Group Type EXPERIMENTAL

Andes virus DNA vaccine

Intervention Type BIOLOGICAL

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.

Placebo

Intervention Type OTHER

Normal saline injections will be administered intramuscularly as matching placebo using the PharmaJet Stratis Needle-Free Injection System

Arm 3 (4 mg ANDV - 3-dose regimen)

1 sentinel subject assigned to the 3-dose regimen will receive 4 mg (2 injections of 0.5 ml (2 mg/0.5 ml each)) of ANDV DNA vaccine intramuscularly into the left and right deltoid on Day 1 in an open label manner, and 4 mg (2 injections of 0.5 ml (2 mg/0.5 ml each)) of ANDV DNA vaccine on Days 29, 169, and matching placebo on Day 57 in double-blind manner.

11 subjects assigned to the 3-dose regimen will receive either 4 mg (2 injections of 0.5 ml (2 mg/0.5 ml each)) of ANDV DNA vaccine intramuscularly into the left and right deltoid on Days 1, 29, 169, and matching placebo on Day 57 (n=9) or matching placebo on Days 1, 29, 57, and 169 (n=2).

Group Type EXPERIMENTAL

Andes virus DNA vaccine

Intervention Type BIOLOGICAL

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.

Placebo

Intervention Type OTHER

Normal saline injections will be administered intramuscularly as matching placebo using the PharmaJet Stratis Needle-Free Injection System

Arm 4 (4 mg ANDV - 4-dose regimen)

1 sentinel subject assigned to the 4-dose regimen will receive 4 mg (2 injections of 0.5 ml (2 mg/0.5 ml each)) of ANDV DNA vaccine intramuscularly into the left and right deltoid on Day 1 in an open label manner, and Days 29, 57 and 169 in double-blind manner.

11 subjects assigned to the 4-dose regimen will receive either 4 mg (2 injections of 0.5 ml (2 mg/0.5 ml each)) of ANDV DNA vaccine intramuscularly into the left and right deltoid on Days 1, 29, 57 and 169 (n=9) or matching placebo on Days 1, 29, 57, and 169 (n=2).

Group Type EXPERIMENTAL

Andes virus DNA vaccine

Intervention Type BIOLOGICAL

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.

Placebo

Intervention Type OTHER

Normal saline injections will be administered intramuscularly as matching placebo using the PharmaJet Stratis Needle-Free Injection System

Interventions

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Andes virus DNA vaccine

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.

Intervention Type BIOLOGICAL

Placebo

Normal saline injections will be administered intramuscularly as matching placebo using the PharmaJet Stratis Needle-Free Injection System

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

1. Provide written informed consent before initiation of any study procedures.
2. Are able to understand and comply with planned study procedures and be available for all study visits/phone calls.
3. Males or non-pregnant females ages 18-49, inclusive.

Exclusion Criteria

5. Oral temperature is less than 100.0 degrees Fahrenheit (37.8 degrees Celsius).
6. Pulse is 47 to 105 beats per minute (bpm), inclusive.
7. Systolic blood pressure (BP) is 85 to 150 mm Hg, inclusive.
8. Diastolic blood pressure (BP) is 55 to 95 mm Hg, inclusive.
9. 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.
10. Urine protein screen is negative or trace.
11. Drug screen for opiates is negative.
12. HgbA1C \< 6.3% at screening.
13. HIV - 1/2 antibody negative.
14. HCV antibody negative.
15. HBsAg negative.
16. Women of childbearing potential\*, 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.

\*Women of childbearing potential are defined as those who have not been sterilized via tubal ligation, bilateral oophorectomy, hysterectomy, or successful Essure(R) placement (permanent, non-surgical, non-hormonal sterilization) with history of documented radiological confirmation test at least 90 days after the procedure (or with use of another birth control method if history of confirmation test not confirmed), AND are still menstruating or \< 1 year since the last menses if perimenoapausal.

\*\*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, non-male sexual relationships, abstinence from sexual intercourse with a male partner, monogamous relationship with a vasectomized partner, male condoms with the use of applied spermicide, intrauterine devices, NuvaRing(R), and licensed hormonal methods such as implants, injectables or oral contraceptives ("the pill").
17. Women of childbearing potential\* must have a negative serum pregnancy test at screening and a negative urine pregnancy test within 24 hours prior to each study vaccination.

\*See definition of women of childbearing potential above.
18. Sexually active male participants whose partner is a woman of childbearing potential\* and has not had a vasectomy\*\* must agree not to father a child until 90 days after the last vaccination\*\*\*.

* See definition of women of childbearing potential above. \*\*Performed \> 1 year prior to screening

* Must agree to use a barrier method of birth control e.g., either condom with spermicidal foam/gel/film/cream or partner reports usage of occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository.
19. 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.
20. Agree not to participate in another clinical trial during the study period.
21. Agree not to donate blood to a blood bank for 3 months after receiving the last study vaccine.


1. 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.
2. 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).
3. 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.
4. Received any licensed live vaccine within 28 days prior to or after each study vaccination.
5. 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.
6. 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.
7. 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
8. Any confirmed or suspected immunosuppressive or immunodeficient condition\* or use of anticancer chemotherapy or radiation therapy (cytotoxic) within 3 years prior to study vaccination.

\*Including HIV infection
9. Administration of chronic (defined as more than 14 days) immunosuppressants or other immune modifying drugs within 6 months of receipt of study vaccine\*.

\*For corticosteroids, this means prednisone, or equivalent, greater than or equal to 0.5 mg/kg/day. Intranasal and topical steroids ARE allowed; daily inhaled steroids for treatment of asthma NOT allowed.
10. History of receipt of a Hantavirus vaccine, including vaccines for Hantaan virus, Puumala virus, or combination of both.
11. Exposed to ANDV\* or plans to travel to an endemic area\*\* from enrollment through 6 months post last vaccination.

\*Residence in an ANDV endemic area in the last 3 years or \> 2 consecutive weeks of travel to an ANDV endemic area\*\* in the last 3 years.

\*\*ANDV endemic areas include Chile, Brazil and Argentina.
12. Any chronic or active neurologic disorder, including seizures and epilepsy, excluding febrile seizures as a child.
13. History of receiving immunoglobulin or other blood product within the 3 months before enrollment in this study.
14. Current or past history of alcohol or drug abuse in the last 5 years.
15. Subjects with autoimmune disorders, chronic inflammatory disorders or neurological disorders with a potential autoimmune correlation.
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 been hospitalized for psychiatric illness, history of suicide attempt, or confinement for danger to self or others within 10 years prior to study vaccination.
18. Have received any antiviral within 3 days of study vaccination.
19. A diagnosis of Type I or II diabetes.
20. Current employee or staff paid entirely or partially by the contract for this trial, or staff who are supervised by the PI or Sub-Investigators.
21. Any condition that would, in the opinion of the Site Investigator or appropriate sub-investigator, is a contraindication to study participation\*.

* Including acute or chronic (persisting for at least 90 days) clinically significant medical disease or condition, that would place the subject at an unacceptable risk of injury, render the subject unable to meet the requirements of the protocol, or may interfere with the evaluation of responses or the subject's successful completion of the study.
Minimum Eligible Age

18 Years

Maximum Eligible Age

49 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Cincinnati Children's Hospital Medical Center - Infectious Diseases

Cincinnati, Ohio, United States

Site Status

Countries

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United States

References

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Paulsen GC, Frenck R Jr, Tomashek KM, Alarcon RM, Hensel E, Lowe A, Brocato RL, Kwilas SA, Josleyn MD, Hooper JW. Safety and Immunogenicity of an Andes Virus DNA Vaccine by Needle-Free Injection: A Randomized, Controlled Phase 1 Study. J Infect Dis. 2024 Jan 12;229(1):30-38. doi: 10.1093/infdis/jiad235.

Reference Type DERIVED
PMID: 37380156 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

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HHSN272201300016I

Identifier Type: -

Identifier Source: secondary_id

16-0119

Identifier Type: -

Identifier Source: org_study_id

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