Phase I, Open Label Dose Ranging Safety Study of GLS-5300 in Healthy Volunteers

Study Overview
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Brief Summary
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The Middle East Respiratory Syndrome Coronavirus (MERS CoV), a virus related to Severe Acute respiratory syndrome coronavirus (SARS CoV), was first recognized as a cause of severe pulmonary infection in 2012. Infection with MERS CoV has been diagnosed in more than 1600 individuals with a mortality rate between 35% and 40%. GLS-5300 is a DNA plasmid vaccine that expresses the MERS CoV spike (S) glycoprotein. This study will evaluate the safety of GLS-5300 at one of three dose levels following a three-injection vaccination regimen followed by electroporation. The study will also assess immune responses over a 1 year period with respect to the generation of antibody and cellular responses.

Detailed Description
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GLS-5300 is a DNA plasmid vaccine that expresses the MERS CoV spike (S) glycoprotein. Following administration of the vaccine, a specialized medical device, CELLECTRA®, will deliver brief electrical pulses in a process known as electroporation (EP), to help move DNA into cells more efficiently.

Official Title
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Phase I, Open-label, Dose Ranging Study to Evaluate the Safety, Tolerability, and Immunogenicity of GLS-5300, Administered IM Followed by Electroporation in Healthy Volunteers

Conditions
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Healthy

Intervention / Treatment
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* Biological: GLS-5300


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-50 years; military, civilian, male and female. Able to provide consent to participate and having signed an Informed Consent Form. Able and willing to comply with all study procedures. Women of child-bearing potential agree to remain sexually abstinent, 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 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 unable to become pregnant; Normal screening ECG or screening ECG with no clinically significant findings; Screening labs must be within normal limits or have only Grade 0-1 findings; No history of clinically significant immunosuppressive or autoimmune disease. 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). Willing to allow storage and future use of samples for MERS CoV related research 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 MERS CoV except if participant is verified to have received placebo; Previous infection with MERS CoV as assessed by self report and solicited exposure history; Administration of any vaccine within 4 weeks of first dose; A BMI greater than or equal to 35; 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 have plans to become pregnant during the course of the study; History of 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; 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 Tattoos covering the injection site area h 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: 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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GLS-5300<br>GLS-5300 at 0.67 mg DNA/dose | Biological: GLS-5300<br> <br> |
| Experimental: GLS-5300 at 2 mg DNA/dose<br>GLS-5300 at 2 mg DNA/dose | Biological: GLS-5300<br> <br> |
| Experimental: GLS-5300 at 6 mg DNA/dose<br>GLS-5300 at 6 mg DNA/dose | Biological: GLS-5300<br> <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 |  | Day0 through Week 60 | 
| Incidence of solicited adverse events after vaccination |  | Day0 through Week 60 | 
| Incidence of unsolicited adverse events after vaccination |  | Day0 through Week 60 | 
| Incidence of serious adverse events |  | Day0 through Week 60 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Binding antibody response to S protein |  | Day0 through Week 60 following the first dose | 
| Neutralizing antibody response to S protein |  | Day0 through Week 60 following the first dose | 
| T cell response |  | Day 0 through Week 60 following the first dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MERS CoV, MERS-CoV, Middle East Respiratory Syndrome, MERS, DNA Vaccine