Evaluation of Safety, Tolerability, and Immunogenicity Study of GLS-6150 in Healthy Volunteers and in Persons Previously Treated for Hepatitis C Virus Infection

Study Overview
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Brief Summary
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Hepatitis C virus (HCV) is an enveloped, single strand, positive sense RNA flavivirus. Infection by HCV is typically chronic, although an estimated  10-20% may spontaneously clear the virus. HCV affects between 1.3 - 2 billion individuals, or 2-3% of the global population. HCV has a seroprevalence of approximately 1% in developed countries such as the US and Korea. Chronic HCV infection leads to hepatic fibrosis and cirrhosis. This Phase I study will evaluate the safety, tolerability and immunogenicity of GLS-6150 administered intradermally (ID) followed by electroporation at 1.0 mg and 2.0 mg/dose assessing 3 and 4-dose regimens.

Detailed Description
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HCV-003 will assess the safety and immunogenicity of GLS-6150 in those previously treated for HCV infection and who have achieved a sustained virologic response (SVR). This study will provide information as to whether GLS-6150 may be useful to prevent re-infection for those successfully cleared of HCV infection. GLS-6150 is a DNA plasmid vaccine that expresses the NS3/4A gene of HCV, NS4B gene of HCV, the NS5A gene of HCV and IL-28B. GLS-6150 will be administered at one of two dose levels (1 mg or 2 mg) and given as a 2 or 3 vaccination priming regimen with a boost vaccination given at 6 months. Immune T cell and serologic responses will be determined after each dose.

Official Title
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A Multi-center, Open-label, Dose-ranging, Phase 1 Study to Evaluate the Safety, Tolerability, and Immunogenicity of GLS-6150, Administered ID and Followed by Cellectra® 2000 Healthy Adults and in Persons Previously Treated for Hepatitis C Virus Infection.

Conditions
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HCV Infection

Intervention / Treatment
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* Biological: GLS-6150


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 19-65 years; HCV seronegative (Group 1 only), HCV seropositive (Groups 2, 3, 4 only) Prior treatment for genotype 1a or 1b Hepatitis C infection with treatment ending (12 weeks after end of DAA treatment, 24 weeks after end of combination treatment with Ribavirin/Interferon) prior to study enrollment and with documented achievement of HCV viral clearance (multiple episodes of treatment for Hepatitis C are allowed, Groups 2, 3, 4 only) Hepatitis C virus PCR negative at screen 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 during this trial, or have a partner who is medically unable to induce pregnancy. 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. 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 prednisone at a dose less than 10 mg/day, or a steroid equivalent). Exclusion Criteria: Administration of an investigational compound either currently or within 3 months of first dose; Administration of any vaccine (excluding influenza vaccination) 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; 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 Hepatitis C serology performed at baseline (Group 1 only) Positive screening PCR test for hepatitis C virus; History of HCV infection with other than genotype 1a or 1b (Group 2, 3 and 4 only) Baseline evidence of kidney disease as measured by creatinine greater than 1.5 mg/dL Baseline screening lab(s) with Grade 2 or higher abnormality; Chronic liver disease, cirrhosis, hemochromatosis, Wilson's disease, alcoholic liver disease, autoimmune hepatitis, or α-1 antitrypsin deficiency(In case of cirrhosis, the person who has been judged F4 grade in Fibroscan); 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 prednisone at a dose equal to or greater than 10 mg/day, or steroid equivalent); Current or anticipated treatment with TNF-α inhibitors such as infliximab, adalimumab, etanercept; Prior major surgery or any radiation therapy within 4 weeks of the first vaccination; Any pre-excitation syndromes, e.g., Wolff-Parkinson-White syndrome; history of PSVT syndrome, history of prolonged QT 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 subjects 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 Hepatitis C virus related research Any illness or condition that in the opinion of the investigator may affect the safety of the subject or the evaluation of any study endpoint.

Ages Eligible for Study
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Minimum Age: 19 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: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1<br>GLS-6150 at 2.0 mg DNA/dose (3 dose prime plus boost) | Biological: GLS-6150<br>* Group 1: GLS-6150 2.0 mg at 0, 4, 12, and 24 weeks (N=8, healthy volunteers); Group 2: GLS-6150 1.0 mg at 0, 4, 12, and 24 weeks (N=8, previously treated for HCV infection); Group 3: GLS-6150 2.0 mg at 0, 4, 12, and 24 weeks (N=8, previously treated for HCV infection); Group 4: GLS-6150 2.0 mg at 0, 8, and 24 weeks (N=8, previously treated for HCV infection)<br>|
| Experimental: Group 2<br>GLS-6150 at 1.0 mg DNA/dose (3 dose prime plus boost) | Biological: GLS-6150<br>* Group 1: GLS-6150 2.0 mg at 0, 4, 12, and 24 weeks (N=8, healthy volunteers); Group 2: GLS-6150 1.0 mg at 0, 4, 12, and 24 weeks (N=8, previously treated for HCV infection); Group 3: GLS-6150 2.0 mg at 0, 4, 12, and 24 weeks (N=8, previously treated for HCV infection); Group 4: GLS-6150 2.0 mg at 0, 8, and 24 weeks (N=8, previously treated for HCV infection)<br>|
| Experimental: Group 3<br>GLS-6150 at 2.0 mg DNA/dose(3 dose prime plus boost) | Biological: GLS-6150<br>* Group 1: GLS-6150 2.0 mg at 0, 4, 12, and 24 weeks (N=8, healthy volunteers); Group 2: GLS-6150 1.0 mg at 0, 4, 12, and 24 weeks (N=8, previously treated for HCV infection); Group 3: GLS-6150 2.0 mg at 0, 4, 12, and 24 weeks (N=8, previously treated for HCV infection); Group 4: GLS-6150 2.0 mg at 0, 8, and 24 weeks (N=8, previously treated for HCV infection)<br>|
| Experimental: Group 4<br>GLS-6150 at 2.0 mg DNA/dose(2 dose prime plus boost) | Biological: GLS-6150<br>* Group 1: GLS-6150 2.0 mg at 0, 4, 12, and 24 weeks (N=8, healthy volunteers); Group 2: GLS-6150 1.0 mg at 0, 4, 12, and 24 weeks (N=8, previously treated for HCV infection); Group 3: GLS-6150 2.0 mg at 0, 4, 12, and 24 weeks (N=8, previously treated for HCV infection); Group 4: GLS-6150 2.0 mg at 0, 8, and 24 weeks (N=8, previously treated for HCV infection)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse events |  | Day0 through up to 28 weeks | 
| Administration (injection) site reactions |  | Day0 through up to 28 weeks | 
| Changes in safety laboratory parameters described by frequency and severity grade |  | Day0 through up to 28 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Antigen specific cellular immune responses to Hepatitis C virus as determined by Interferon-gamma (IFN-γ) ELISpot and/or FACS assay |  | Day0 through up to 28 weeks | 
| Binding antibody titers to the HCV non-structural proteins (NS3, NS4, NS5) measured by ELISA |  | Day0 through up to 28 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HCV, Hepatitis C Virus, Vaccine, DNA