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.
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 32
- 试验地点
- 2
- 主要终点
- Incidence of adverse events
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 19 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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).
排除标准
- •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.
研究组 & 干预措施
Group 4
GLS-6150 at 2.0 mg DNA/dose(2 dose prime plus boost)
干预措施: GLS-6150 (Biological)
Group 3
GLS-6150 at 2.0 mg DNA/dose(3 dose prime plus boost)
干预措施: GLS-6150 (Biological)
Group 2
GLS-6150 at 1.0 mg DNA/dose (3 dose prime plus boost)
干预措施: GLS-6150 (Biological)
Group 1
GLS-6150 at 2.0 mg DNA/dose (3 dose prime plus boost)
干预措施: GLS-6150 (Biological)
结局指标
主要结局
Incidence of adverse events
时间窗: Day0 through up to 28 weeks
Changes in safety laboratory parameters described by frequency and severity grade
时间窗: Day0 through up to 28 weeks
Administration (injection) site reactions
时间窗: Day0 through up to 28 weeks
次要结局
- 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)