evaluation of safety, tolerability, and immunogenicity study of gls-6150 in healthy volunteers and in persons previously treated for hepatitis c virus infection

Conditions: HCV Infection

Summary: 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.

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.

Eligibility criteria:
inclusion criteria: 1. age 19-65 years; 2. hcv seronegative (group 1 only), hcv seropositive (groups 2, 3, 4 only) 3. 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) 4. hepatitis c virus pcr negative at screen 5. able to provide consent to participate and having signed an informed consent form (icf); 6. able and willing to comply with all study procedures; 7. 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. 8. normal screening ecg or screening ecg with no clinically significant findings; 9. screening laboratory must be within normal limits or have only grade 0-1 findings; 10. no history of clinically significant immunosuppressive or autoimmune disease. 11. 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: 1. administration of an investigational compound either currently or within 3 months of first dose; 2. administration of any vaccine (excluding influenza vaccination) within 4 weeks of first dose; 3. administration of any monoclonal or polyclonal antibody product within 4 weeks of the first dose 4. administration of any blood product within 3 months of first dose; 5. pregnancy or breast feeding or plans to become pregnant during the course of the study; 6. 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; 7. positive hepatitis c serology performed at baseline (group 1 only) 8. positive screening pcr test for hepatitis c virus; 9. history of hcv infection with other than genotype 1a or 1b (group 2, 3 and 4 only) 10. baseline evidence of kidney disease as measured by creatinine greater than 1.5 mg/dl 11. baseline screening lab(s) with grade 2 or higher abnormality; 12. 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); 13. immunosuppressive illness including hematologic malignancy, history of solid organ or bone marrow transplantation; 14. 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); 15. current or anticipated treatment with tnf-α inhibitors such as infliximab, adalimumab, etanercept; 16. prior major surgery or any radiation therapy within 4 weeks of the first vaccination; 17. any pre-excitation syndromes, e.g., wolff-parkinson-white syndrome; history of psvt syndrome, history of prolonged qt syndrome; 18. presence of a cardiac pacemaker or automatic implantable cardioverter defibrillator (aicd) 19. metal implants within 20 cm of the planned site(s) of injection; 20. presence of keloid scar formation or hypertrophic scar as a clinically significant medical condition at the planned site(s) of injection. 21. prisoner or subjects who are compulsorily detained (involuntary incarceration) for treatment of either a physical or psychiatric illness; 22. 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 23. not willing to allow storage and future use of samples for hepatitis c virus related research 24. 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.

Keywords: hepatitis c virus hcv vaccine dna