VRC 320: A Phase I, Randomized Clinical Trial to Evaluate the Safety and Immunogenicity of a Zika Virus DNA Vaccine, VRC-ZKADNA090-00-VP, Administered Via Needle and Syringe or Needle-free Injector, PharmaJet, inHealthy Adults

Study Overview
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Brief Summary
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Background: People get Zika virus from infected mosquitos. They usually don t get very sick. But birth defects were reported in babies born to mothers who had Zika infection. In rare cases, people with Zika infection had a nervous system disease that causes severe muscle weakness and can be life threatening. A new vaccine made from DNA in the code for a Zika virus protein could help the body build an immune response against the virus. Objectives: To see if a new vaccine against Zika virus disease is safe and causes any side effects. To study specific immune responses to the vaccine. Eligibility: Healthy people ages 18-50 Design: Participants will be screened with: Medical history Physical exam Urine tests Participants will have 18 visits over 2 years. Participants will be randomly assigned to 1 of 3 groups. All will get 3 vaccines at 3 separate monthly visits. They will receive the vaccine in the upper arm muscle. Some will get it by needle and syringe, others by a device that uses high pressure to push the vaccine through the skin. Vaccine visits last 4-6 hours. Participants will get a thermometer to measure their temperature and a ruler to measure any skin changes at the injection site. They will record this data for 7 days after each injection. Other visits last 1-2 hours. These include: Evaluation of any health changes or problems Blood tests: Some samples may be used for future research. Participants with side effects may have extra visits. ...

Detailed Description
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STUDY DESIGN: This is a Phase I, randomized clinical study to evaluate the safety, tolerability, and immunogenicity of a 3 dose vaccination regimen with the Zika virus (ZIKVwt) DNA vaccine, VRC-ZKADNA090-00-VP. Subjects will be randomized to one of three groups to receive a full 4 mg dose: 1) full dose by one intramuscular (IM) injection with needle and syringe; 2) split dose given as two 0.5 mL IM injections with needle and syringe; 3) split dose given as two 0.5 mL IM injections with PharmaJet, a needle-free injection device. The primary hypothesis is that the investigational ZIKVwt DNA vaccine will be safe and well tolerated in healthy adults. A secondary hypothesis is that the vaccine will elicit a ZIKV-specific immune response. The primary objectives are to evaluate the safety and tolerability of the vaccine in healthy adults. Secondary objectives are related to the immunogenicity of the vaccine and vaccination regimens. PRODUCT DESCRIPTION: The investigational vaccine, VRC-ZKADNA090-00-VP, was developed by the Vaccine Research Center (VRC), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH) and is composed of a single closed-circular DNA plasmid (VRC 5283) that encodes the wild type (wt) precursor membrane M (prM) and envelope (E) proteins from the H/PF/2013 strain of ZIKV. ZIKVwt SUBJECTS: Healthy adults 18 to 50 years of age. STUDY PLAN: Forty-five subjects will be enrolled at the NIH Clinical Center and randomized to 3 groups to receive study product on Day 0, Week 4 and Week 8. The protocol requires about 18 scheduled clinic visits and a telephone follow-up contact after each study product administration. Solicited reactogenicity will be evaluated using a 7-day diary card. Assessment of vaccine safety will include clinical observation and monitoring of hematological and chemical parameters at clinical visits throughout the study. VRC 320 STUDY SCHEMA: Group 1: Administration Method = Single Dose Needle and Syringe; Subjects = 15; Administration Schedule = Day 0 (ZIKVwt DNA(1 (1 mL) injection)), Week 4 (ZIKVwt DNA (1 (1 mL) injection)), Week 8 (ZIKVwt DNA (1 (1 mL) injection)) Group 2: Administration Method = Split Dose Needle and Syringe; Subjects = 15; Administration Schedule = Day 0 (ZIKVwt DNA(2 (0.5 mL) injections)), Week 4 (ZIKVwt DNA (2 (0.5 mL) injections)), Week 8 (ZIKVwt DNA (2 (0.5 mL) injections)) Group 3: Administration Method = Split Dose PharmaJet; Subjects = 15; Administration Schedule = Day 0 (ZIKVwt DNA(2 (0.5 mL) injections)), Week 4 (ZIKVwt DNA (2 (0.5 mL) injections)), Week 8 (ZIKVwt DNA (2 (0.5 mL) injections)) Subjects Total = 45 (All injections total a dose of 4 mg. ** Up to 50 total enrollments are permitted if additional subjects are needed to assess safety or immunogenicity.) STUDY DURATION: Subjects will be evaluated for safety and immune responses throughout the study for 44 weeks following the first vaccine administration. Durability of immune responses will be evaluated at two long term follow-up visits, occurring at 18 and 24 months

Official Title
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VRC 320: A Phase I, Randomized Clinical Trial to Evaluate the Safety and Immunogenicity of a Zika Virus DNA Vaccine, VRC-ZKADNA090-00-VP, Administered Via Needle and Syringe or Needle-free Injector, PharmaJet, in Healthy Adults

Conditions
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Prevention of Zika Infection, Zika-Specific Immune Response

Intervention / Treatment
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* Biological: VRC-ZKADNA090-00-VP


Participation Criteria
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Eligibility Criteria
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INCLUSION CRITERIA: A subject must meet all of the following criteria: 18 to 50 years old Available for clinic visits for 24 months after enrollment Able to provide proof of identity to the satisfaction of the study clinician completing the enrollment process Able and willing to complete the informed consent process Willing to donate blood for sample storage to be used for future research In good general health without clinically significant medical history Physical examination and laboratory results without clinically significant findings and a Body Mass Index (BMI) less than or equal to 40 within the 56 days prior to enrollment Agrees not to receive licensed or investigational flavivirus vaccines through 4 weeks after last product administration Laboratory Criteria within 56 days prior to enrollment: Hemoglobin within institutional normal limits or accompanied by the site Principal Investigator (PI) or designee approval WBC and differential either within institutional normal range or accompanied by site PI or designee approval Total lymphocyte count greater than or equal to 800 cells/mm^3 Platelets = 125,000 - 500,000/mm^3 Alanine aminotransferase (ALT) less than or equal to 1.25 x institutional upper limit of normal (ULN) Serum creatinine less than or equal to 1.1 x institutional ULN Negative for HIV infection by an FDA approved method of detection Criteria applicable to women of childbearing potential: Negative human chorionic gonadotropin (beta-HCG) pregnancy test (urine or serum) on day of enrollment Agrees to use an effective means of birth control from at least 21 days prior to enrollment through 12 weeks after the last study vaccination EXCLUSION CRITERIA: A subject will be excluded if one or more of the following conditions apply: Female-specific: Breast-feeding or planning to become pregnant while participating through 12 weeks after the last study vaccination Subject has received any of the following: More than 10 days of systemic immunosuppressive medications or cytotoxic medications within the 4 weeks prior to enrollment or any within the 14 days prior to enrollment Blood products within 16 weeks prior to enrollment Inactivated vaccines within 2 weeks prior to enrollment Live attenuated vaccines within 4 weeks prior to enrollment Investigational research products within 4 weeks prior to enrollment or planning to receive investigational products while on the study Current allergen immunotherapy with antigen injections, unless on maintenance schedule Current anti-TB prophylaxis or therapy Subject has a history of any of the following clinically significant conditions: Laboratory confirmed ZIKV infection by self-report at the time of enrollment Serious reactions to vaccines that preclude receipt of study vaccinations as determined by the site investigator Hereditary angioedema, acquired angioedema, or idiopathic forms of angioedema Asthma that is not well controlled Diabetes mellitus (type I or II), with the exception of gestational diabetes Evidence of autoimmune disease or immunodeficiency Idiopathic urticaria within the past year Hypertension that is not well controlled Bleeding disorder diagnosed by a doctor (e.g. factor deficiency, coagulopathy, or platelet disorder requiring special precautions) or significant bruising or bleeding difficulties with IM injections or blood draws Malignancy that is active or history of malignancy that is likely to recur during the period of the study Seizure disorder other than: 1) febrile seizures, 2) seizures secondary to alcohol withdrawal more than 3 years ago, or 3) seizures that have not required treatment within the last 3 years Asplenia, functional asplenia or any condition resulting in the absence or removal of the spleen Guillain-Barre Syndrome, Bell's palsy or similar neurological conditions Psychiatric condition that precludes compliance with the protocol; past or present psychoses; or within 5 years prior to enrollment, a history of suicide plan or attempt Any medical, psychiatric, social condition, occupational reason or other responsibility that, in the judgment of the investigator, is a contraindication to protocol participation or impairs a volunteer's ability to give informed consent

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1<br>ZIKV DNA vaccine administered IM via needle and syringe at a single dosage of 4 mg on Day 0, week 4 and week 8. | Biological: VRC-ZKADNA090-00-VP<br>* VRC-ZKADNA090-00-VP is an investigational ZIKV DNA vaccine that is intended to prevent Zika virus infection.<br>|
| Experimental: Group 2<br>ZIKV DNA vaccine administered IM via needle and syringe as a split dose of two .5 ml injections on Day 0, week 4 and week 8. | Biological: VRC-ZKADNA090-00-VP<br>* VRC-ZKADNA090-00-VP is an investigational ZIKV DNA vaccine that is intended to prevent Zika virus infection.<br>|
| Experimental: Group 3<br>ZIKV DNA vaccine administered IM via needle-free injection device, PharmaJet, as a split dose of two .5 ml injections on Day 0, week 4 and week 8. | Biological: VRC-ZKADNA090-00-VP<br>* VRC-ZKADNA090-00-VP is an investigational ZIKV DNA vaccine that is intended to prevent Zika virus infection.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the safety and tolerability of v ZIKV DNA vaccine administered at 4mg IM by needle and syringe. |  | Through 44 weeks of study participation. | 
| To evaluate the safety and tolerability of ZIKV DNA vaccine administered at 4 mg IM by Pharma jet. |  | Through 44 weeks of study participation. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the magnitude and the frequency of ZIKV-specific antibody response as measured by neutralization assay. |  | Four weeks after the first, second and third injections for each regimen. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Zika Infection, Immune Response, Flavivirus, Arthropod-Borne Virus