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

NCT ID: NCT03674125

Last Updated: 2020-05-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 32 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-09-04
• Study Completion Date: 2020-05-04

Brief 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.

Detailed Description

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.

Conditions

HCV Infection

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Group 1

GLS-6150 at 2.0 mg DNA/dose (3 dose prime plus boost)

Group Type: EXPERIMENTAL

GLS-6150

Intervention Type: BIOLOGICAL

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)

Group 2

GLS-6150 at 1.0 mg DNA/dose (3 dose prime plus boost)

Group Type: EXPERIMENTAL

GLS-6150

Intervention Type: BIOLOGICAL

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)

Group 3

GLS-6150 at 2.0 mg DNA/dose(3 dose prime plus boost)

Group Type: EXPERIMENTAL

GLS-6150

Intervention Type: BIOLOGICAL

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)

Group 4

GLS-6150 at 2.0 mg DNA/dose(2 dose prime plus boost)

Group Type: EXPERIMENTAL

GLS-6150

Intervention Type: BIOLOGICAL

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)

Interventions

GLS-6150

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)

Intervention Type: BIOLOGICAL

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.

• Minimum Eligible Age: 19 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

GeneOne Life Science, Inc.

INDUSTRY

Sponsor Role: lead

Inovio Pharmaceuticals

INDUSTRY

Sponsor Role: collaborator

Responsible Party

Responsibility Role: SPONSOR

Locations

Pusan National University Hospital

Busan, , South Korea

Yonsei University Health System, Severance Hospital

Seoul, , South Korea

Countries

South Korea

Other Identifiers

HCV-003

Identifier Type: -

Identifier Source: org_study_id