GLS-5700 in Healthy Volunteers

Study Overview
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Brief Summary
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The clinical trial will assess the safety, tolerability, and immunogenicity of GLS-5700. GLS-5700 is a synthetic DNA plasmid vaccine against the Zika virus. ZIKA-001 is the first in man clinical trial of this vaccine which encodes for the premembrane-membrane and envelope regions of Zika virus. Zika virus, first discovered in the Zika forest in 1947, has caused a large epidemic in South America, Central America, and the Caribbean islands commencing in late 2014 or early 2015. Zika virus can cause significant neurologic disease to include Guillain Barre Syndrome in adults and microcephaly and other birth defects among children born to mothers who are infected during pregnancy. At present no vaccines or treatments have been approved for Zika virus infection.

Detailed Description
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GLS-5700 contains a single plasmid containing DNA encoding for pre-membrane and envelope (prME) proteins of the Zika virus.

Official Title
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Phase I, Open-label, Dose-Ranging Study to Evaluate the Safety, Tolerability, and Immunogenicity of GLS-5700 Administered ID Followed by EP in Dengue Virus-Naïve Adults

Conditions
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Healthy

Intervention / Treatment
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* Biological: GLS-5700


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-65 years; Able to provide consent to participate and having signed an Informed Consent Form (ICF); Able and willing to comply with all study procedures; Women of child-bearing potential agree to use medically effective contraception (oral contraception, barrier methods, spermicide, etc.) or have a partner who is sterile from enrollment to 3 months following the last injection, or have a partner who is medically unable to induce pregnancy. Sexually active men who are considered sexually fertile must agree to use either a barrier method of contraception during the study, and agree to continue the use for at least 3 months following the last injection, or have a partner who is permanently sterile or is medically unable to become pregnant; Normal screening ECG or screening ECG with no clinically significant findings; Screening laboratory must be within normal limits or have only Grade 0-1 findings; No history of clinically significant immunosuppressive or autoimmune disease. No history of dengue virus vaccination or illness; no history of yellow fever vaccination. Dengue seronegative at baseline by screening laboratory evaluation Not currently or within the previous 4 weeks taking immunosuppressive agents (excluding inhaled, topical skin and/or eye drop-containing corticosteroids, low-dose methotrexate, or corticosteroids at a dose less than 20 mg/day). Exclusion Criteria: Administration of an investigational compound either currently or within 30 days of first dose; Previous receipt of an investigational product for the treatment or prevention of Zika virus except if participant is verified to have received placebo; Administration of any vaccine within 4 weeks of first dose; Administration of any monoclonal or polyclonal antibody product within 4 weeks of the first dose Administration of any blood product within 3 months of first dose; Pregnancy or breast feeding or plans to become pregnant during the course of the study; Positive serologic result for dengue virus (any serotype) or history of receipt of either dengue virus or yellow fever virus vaccination at any time in the past; Positive serologic test for HIV, hepatitis B surface antigen (HBsAg); or any potentially communicable infectious disease as determined by the Principal Investigator or Medical Monitor; Positive serologic test for hepatitis C (exception: successful treatment with confirmation of sustained virologic response); Baseline evidence of kidney disease as measured by creatinine greater than 1.5 (CKD Stage II or greater); Baseline screening lab(s) with Grade 2 or higher abnormality, except for Grade 2 creatinine; Chronic liver disease or cirrhosis; Immunosuppressive illness including hematologic malignancy, history of solid organ or bone marrow transplantation; Current or anticipated concomitant immunosuppressive therapy (excluding inhaled, topical skin and/or eye drop-containing corticosteroids, low-dose methotrexate, or corticosteroids at a dose less than 20 mg/day); Current or anticipated treatment with TNF-α inhibitors such as infliximab, adalimumab, etanercept; Prior major surgery or any radiation therapy within 4 weeks of group assignment; Any pre-excitation syndromes, e.g., Wolff-Parkinson-White syndrome; Presence of a cardiac pacemaker or automatic implantable cardioverter defibrillator (AICD) Metal implants within 20 cm of the planned site(s) of injection; Presence of keloid scar formation or hypertrophic scar as a clinically significant medical condition at the planned site(s) of injection. Prisoner or participants who are compulsorily detained (involuntary incarceration) for treatment of either a physical or psychiatric illness; Active drug or alcohol use or dependence that, in the opinion of the investigator, would interfere with adherence to study requirements or assessment of immunologic endpoints; or Not willing to allow storage and future use of samples for Zika virus related research Any illness or condition that in the opinion of the investigator may affect the safety of the participant or the evaluation of any study endpoint. -

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GLS-5700 at 1 mg<br>DNA/dose | Biological: GLS-5700<br>* GLS-5700 contains a single plasmid containing DNA encoding for pre-membrane and envelope (prME) proteins of the Zika virus<br>|
| Experimental: GLS-5700 at 2 mg<br>DNA/dose | Biological: GLS-5700<br>* GLS-5700 contains a single plasmid containing DNA encoding for pre-membrane and envelope (prME) proteins of the Zika virus<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean change from baseline in safety laboratory measures |  | Day 0 through Week 60 | 
| Incidence of solicited adverse events after vaccination |  | Day 0 through Week 60 | 
| Incidence of unsolicited adverse events after vaccination |  | Day 0 through Week 60 | 
| Incidence of serious adverse events |  | Day 0 through Week 60 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Binding antibody titers to Zika envelope |  | Day 0 through Week 60 following first dose | 
| Neutralizing antibody response against Zika virus |  | Day 0 through Week 60 following first dose | 
| T cell response |  | Day 0 through Week 60 following first dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Zika, Vaccine, DNA