Study to Evaluate the Safety, Tolerability, and Immunogenicity of Hantaan and Puumala Virus DNA Vaccines

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Hemorrhagic Fever With Renal Syndrome

Intervention / Treatment
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* Biological: Vaccine/device combination for prevention of HFRS


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 49 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PUUV DNA Vaccine<br>This group will receive Puumala Virus DNA Vaccine only | Biological: Vaccine/device combination for prevention of HFRS<br>* 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<br>* Other names: Hantavirus;|
| Experimental: HTNV + PUUV<br>This group will receive a 1:1 mixture of HTNV and PUUV DNA Vaccines | Biological: Vaccine/device combination for prevention of HFRS<br>* 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<br>* Other names: Hantavirus;|
| Experimental: HTNV DNA Vaccine<br>This group will receive Hantaan Virus DNA Vaccine only | Biological: Vaccine/device combination for prevention of HFRS<br>* 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<br>* Other names: Hantavirus;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline for solicited adverse events after each vaccination | • The nature, frequency, and severity of local and systemic AEs or SAEs associated with TDS-IM-EP-based administration of HTNV and PUUV vaccines | Day 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 | 
| Change from baseline for Unsolicited adverse events after each vaccination | • The nature, frequency, and severity of local and systemic AEs or SAEs associated with TDS-IM-EP-based administration of HTNV and PUUV vaccines | 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 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in neutralizing antibody levels from baseline to post vaccination | 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. | Day 0, 28, 56, 84, 140, 180 and 240 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HFRS