Study to Evaluate the Safety, Tolerability, and Immunogenicity of Hantaan and Puumala Virus DNA Vaccines (HTNV/PUUV)

This study has been completed.
Sponsor:
Collaborators:
United States Army Medical Research Institute of Infectious Diseases
United States Army Medical Materiel Development Activity
Ichor Medical Systems Incorporated
Walter Reed Army Institute of Research (WRAIR)
Information provided by (Responsible Party):
U.S. Army Medical Research and Materiel Command
ClinicalTrials.gov Identifier:
NCT01502345
First received: December 23, 2011
Last updated: January 30, 2013
Last verified: January 2013
  Purpose

The purpose of this study is:

• To assess safety and tolerability of the HTNV and PUUV DNA vaccines, pWRG/HTN-M(x) and pWRG/PUUV-M(s2), administered intramuscularly using a TDS-IM electroporation device

Secondary:

• To evaluate clinical immunogenicity of the HTNV and PUUV DNA vaccines, pWRG/HTN-M(x) and pWRG/PUUV-M(s2), including an assessment of the acute procedure tolerability when administered with the TDS-IM electroporation.


Condition Intervention Phase
Hemorrhagic Fever With Renal Syndrome
Biological: Vaccine/device combination for prevention of HFRS
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Subject)
Primary Purpose: Prevention
Official Title: Phase 1 Study to Evaluate the Safety, Tolerability, and Immunogenicity of Hantaan and Puumala Virus DNA Vaccines, pWRG/HTN-M(x) and pWRG/PUU-M(s2), for Prevention of Hemorrhagic Fever With Renal Syndrome Administered to Healthy Adult Volunteers Using the TDS-IM Electroporation Delivery Device

Resource links provided by NLM:


Further study details as provided by U.S. Army Medical Research and Materiel Command:

Primary Outcome Measures:
  • Change from baseline for solicited adverse events after each vaccination [ Time Frame: Day 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 ] [ Designated as safety issue: Yes ]
    • The nature, frequency, and severity of local and systemic AEs or SAEs associated with TDS-IM-EP-based administration of HTNV and PUUV vaccines

  • Change from baseline for Unsolicited adverse events after each vaccination [ Time Frame: Day 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24 ] [ Designated as safety issue: Yes ]
    • The nature, frequency, and severity of local and systemic AEs or SAEs associated with TDS-IM-EP-based administration of HTNV and PUUV vaccines


Secondary Outcome Measures:
  • Change in neutralizing antibody levels from baseline to post vaccination [ Time Frame: Day 0, 28, 56, 84, 140, 180 and 240 ] [ Designated as safety issue: No ]
    The endpoint used to measure immunogenicity of the HTNV and PUUV DNA vaccines is the production of neutralizing antibody titers to HTNV and PUUV (PRNT50 ≥ 1:20). Initial immunogenicity results will be analyzed on the basis of intention-to-treat, in which the outcomes of all subjects who had at least one dose of vaccine will be analyzed with the group to which they were originally assigned, regardless of whether they completed the study. Subsequently, all subjects who completed the 8-month study and have serologic data will be included in the analysis of immunogenicity.


Enrollment: 31
Study Start Date: January 2012
Study Completion Date: January 2013
Primary Completion Date: January 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: PUUV DNA Vaccine
This group will receive Puumala Virus DNA Vaccine only
Biological: Vaccine/device combination for prevention of HFRS
PUUV DNA Vaccine, 2.0mg/ml TDS-IM injection HTNV DNA Vaccine, 2.0 mg/ml TDS-IM injection HTNV + PUUV Vaccine mixture, 1.0mg/mL + 1.0mg/ml TDS-IM injection
Other Names:
  • Ichor Tri-Grid Delivery System
  • Hantavirus
Experimental: HTNV + PUUV
This group will receive a 1:1 mixture of HTNV and PUUV DNA Vaccines
Biological: Vaccine/device combination for prevention of HFRS
PUUV DNA Vaccine, 2.0mg/ml TDS-IM injection HTNV DNA Vaccine, 2.0 mg/ml TDS-IM injection HTNV + PUUV Vaccine mixture, 1.0mg/mL + 1.0mg/ml TDS-IM injection
Other Names:
  • Ichor Tri-Grid Delivery System
  • Hantavirus
Experimental: HTNV DNA Vaccine
This group will receive Hantaan Virus DNA Vaccine only
Biological: Vaccine/device combination for prevention of HFRS
PUUV DNA Vaccine, 2.0mg/ml TDS-IM injection HTNV DNA Vaccine, 2.0 mg/ml TDS-IM injection HTNV + PUUV Vaccine mixture, 1.0mg/mL + 1.0mg/ml TDS-IM injection
Other Names:
  • Ichor Tri-Grid Delivery System
  • Hantavirus

Detailed Description:

The study will enroll 3 randomized groups of 9 subjects each, along with 3 alternates, for a total of 30 subjects. The study will include one group of subjects injected with the HTNV DNA vaccine, one group injected with the PUUV DNA vaccine, and one group injected with both HTNV and PUUV DNA vaccines (mixed), administered with the Ichor TDS-IM device. Subjects will receive one dose of vaccine on Days 0, 28, and 56 and will be followed until Day 240. Subjects will complete post-injection memory aids for 14 days after each injection.

Subjects will be evaluated for safety and immune response throughout the study.

  Eligibility

Ages Eligible for Study:   18 Years to 49 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Healthy adult male or non-pregnant, non-lactating female, ages 18-49 (inclusive) at time of screening
  • Have demonstrated adequate comprehension of the protocol, by achieving a score of at least 80% correct on a short multiple-choice quiz

    • Individuals who fail to achieve a passing score on the initial quiz will be given the opportunity to retest after a review of protocol information
    • Individuals who fail the comprehension assessment for the second time will not be enrolled
  • Have provided written informed consent before screening
  • Free of clinically significant health problems, as determined by pertinent medical history and clinical examination before entry into the study
  • Available and able to participate for all study visits and procedures
  • If sexually active, known to be at least 1 year post-menopausal, or willing to use an effective method of contraception (e.g., birth control pill, diaphragm, cervical cap, intrauterine device, condom, or anatomical sterility [in self or partner]) from the date of screening until at least 6 months after the last vaccination
  • Negative hantavirus IgG antibody test result at screening (ELISA)

Exclusion Criteria:

  • History or serologic evidence of prior infection with either HTNV or PUUV virus, or prior participation in a HTNV or PUUV virus vaccine trial
  • History of severe local or systemic reactions to any vaccination or a history of severe allergic reactions
  • Any serologic evidence of hepatitis B or C infection
  • Ongoing participation in another clinical trial
  • Receipt or planned receipt of any vaccination, experimental or otherwise, within the period 30 days prior to initial injection through 60 days after the Day 70 follow-up (approximately a 6 month period in total)
  • 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 injection 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, hepatic or renal functional abnormality as determined by the investigator based on medical history, physical examination, EKG, 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 confirmed or suspected immunosuppressive or immunodeficient condition, including human immunodeficiency virus 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
    • Inhaled 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 abuse as defined by the American Psychiatric Association in DSM IV (Diagnostic and Statistical Manual of Mental Disorders-4th edition)
  • Chronic or active illicit and/or intravenous drug use
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01502345

Locations
United States, Maryland
Walter Reed Army Institute of Research
Silver Spring, Maryland, United States, 20910
Sponsors and Collaborators
U.S. Army Medical Research and Materiel Command
United States Army Medical Research Institute of Infectious Diseases
United States Army Medical Materiel Development Activity
Ichor Medical Systems Incorporated
Walter Reed Army Institute of Research (WRAIR)
Investigators
Principal Investigator: James E Moon, MD WRAIR, Clinical Trials Center
  More Information

No publications provided

Responsible Party: U.S. Army Medical Research and Materiel Command
ClinicalTrials.gov Identifier: NCT01502345     History of Changes
Other Study ID Numbers: A-17088, WRAIR 1854, S-11-12
Study First Received: December 23, 2011
Last Updated: January 30, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by U.S. Army Medical Research and Materiel Command:
HFRS

Additional relevant MeSH terms:
Syndrome
Hemorrhagic Fevers, Viral
Hemorrhagic Fever with Renal Syndrome
Disease
Pathologic Processes
RNA Virus Infections
Virus Diseases
Hantavirus Infections
Bunyaviridae Infections

ClinicalTrials.gov processed this record on September 18, 2014