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.

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.

开始日期2018-09-04

申办/合作机构

GeneOne Life Science, Inc.

[+1]

NCT02027116 / Completed临床1期

Multi-center, Open-label, Dose Escalation, Phase I Trial to Evaluate the Safety, Tolerability and Immunogenicity of VGX-6150 for Second-line Therapy of Chronic Hepatitis C Infection

To evaluate the safety, tolerability and immunogenicity of VGX-6150 as second-line therapy in chronic hepatitis C patients

开始日期2014-01-01

申办/合作机构

GeneOne Life Science, Inc.

[+1]

100 项与 INO-8000 相关的临床结果

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100 项与 INO-8000 相关的转化医学

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100 项与 INO-8000 相关的专利（医药）

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项与 INO-8000 相关的文献（医药）

2023-03-01·Cancer Prevention Research

Phase I Trial of a Therapeutic DNA Vaccine for Preventing Hepatocellular Carcinoma from Chronic Hepatitis C Virus (HCV) Infection

Article

作者: Weiner, David B. ; Rodriguez, Luz Maria ; Strand, Carrie A. ; Gillespie, Elisabeth ; Zahrieh, David ; Marrero, Idania ; Mandrekar, Sumithra J. ; Jacobson, Jeffrey M. ; Umar, Asad ; Pawlicki, Jan M. ; Roberts, Lewis R. ; Barranco, Eduardo ; Cruz-Correa, Marcia ; Limburg, Paul J. ; Boyer, Jean ; Pungpapong, Surakit ; Sylvester, Albert J. ; Kraynyak, Kimberly A. ; Richmond, Ellen ; Morrow, Matthew P.

AbstractChronic hepatitis C can lead to cirrhosis and hepatocellular carcinoma. We studied the safety and immunogenicity of a novel therapeutic hepatitis C virus (HCV) genotype 1a/1b consensus DNA vaccine, INO-8000, encoding HCV NS3, NS4A, NS4B, and NS5A proteins alone or co-administered with DNA-encoding IL12 (INO-9012), a human cytokine that stimulates cellular immune function, in individuals with chronic hepatitis C. This was a phase I, multisite dose-escalation trial with an expansion cohort evaluating doses of 0, 0.3, 1.0, and 3.0 mg of INO-9012 (IL12 DNA) as an addition to 6.0 mg of (INO-8000; HCV DNA vaccine). Vaccines were administered by intramuscular injection followed by electroporation at study entry and at weeks 4, 12, and 24. HCV-specific CD4+ and CD8+ T-cell immune responses were measured by IFNγ ELISpot and flow cytometry–based assays. Transient, mild-to-moderate injection site reactions unrelated to IL12 DNA dose were common. Increases in HCV-specific IFNγ production occurred in 15/20 (75%) participants. Increases in the frequency of HCV-specific CD4+ and CD8+ T cells occurred at all dose levels, with the greatest increases seen at 1.0 mg of INO-9012. HCV-specific CD8+ and CD4+ T-cell activities increased in 16/18 (89%) and 14/17 (82%) participants with available data, respectively. The vaccine regimen was safe and induced HCV-specific CD4+ and CD8+ cellular immune responses of modest magnitude in most HCV-infected participants. The addition of 1.0 mg of IL12 DNA provided the best enhancement of immune responses. The vaccine regimen had little effect on controlling HCV viremia.Prevention Relevance:The administration of IL12 DNA along with a hepatitis C viral antigen DNA vaccine enhanced the HCV-specific immune responses induced by the vaccine in individuals with chronic hepatitis C, an important cause of hepatocellular carcinoma. IL12 could be an effective adjuvant in vaccines targeting HCV and other oncogenic viruses.

2020-07-01·Journal of Hepatology1区 · 医学

IFNL3-adjuvanted HCV DNA vaccine reduces regulatory T cell frequency and increases virus-specific T cell responses

1区 · 医学

Article

作者: Jeong, Moonsup ; Weiner, David B ; Sung, Pil Soo ; Koh, June Young ; Park, Su-Hyung ; Lee, Hoyoung ; Han, Ji Won ; Shin, Eui-Cheol ; Ahn, Sang Hoon ; Maslow, Joel N ; Hong, Seon-Hui ; Lee, Hyojin ; Heo, Jeong ; White, Scott

BACKGROUND & AIMSAlthough direct-acting antiviral (DAA) treatment results in a sustained virologic response (SVR) in most patients with chronic HCV infection, they are at risk of re-infection. Moreover, the immune system is not completely normalized even after SVR (e.g. increased regulatory T [Treg] cell frequency). We developed a DNA vaccine, GLS-6150, to prevent re-infection of patients with DAA-induced SVR and evaluated its safety and immunogenicity in individuals with chronic HCV infection.METHODSGLS-6150 consists of plasmids encoding HCV non-structural proteins (NS3-NS5A) and adjuvant IFNL3. The vaccine was administered 4 times at 4-weekly intervals to 3 groups (1, 3, or 6 mg/vaccination; n = 6 per group), followed by a 6 mg boost at 24 weeks (n = 14). Peripheral blood T cell responses were evaluated by interferon (IFN)-γ enzyme-linked immunospot assays, intracellular cytokine staining, and major histocompatibility complex class-I (MHC-I) dextramer staining. Treg cell frequency was assessed by flow cytometry.RESULTSSevere adverse events or vaccine discontinuation were not reported. The IFN-γ spot-forming cells specific to NS3-NS5A were increased by GLS-6150. Both CD4⁺ and CD8⁺ T cells produced multiple cytokines. However, the frequency and phenotype of HCV-specific MHC-I dextramer⁺CD8⁺ T cells were not changed. Interestingly, the frequency of Treg cells, particularly activated Treg cells, was decreased by GLS-6150, as expected from previous reports that IFNL3 adjuvants decrease Treg cell frequency. Ex vivo IFN-λ3 treatment reduced Treg frequency in pre-vaccination peripheral blood mononuclear cells. Finally, Treg cell frequency inversely correlated with HCV-specific, IFN-γ-producing T cell responses in the study participants.CONCLUSIONSWe demonstrate that GLS-6150 decreases Treg cell frequency and enhances HCV-specific T cell responses without significant side effects. A phase I clinical trial of GLS-6150 is currently underway in patients with DAA-induced SVR.CLINICAL TRIAL NUMBERNCT02027116.LAY SUMMARYAlthough direct-acting antivirals (DAAs) are successfully used for the treatment of chronic hepatitis C virus (HCV) infection, a prophylactic HCV vaccine needs to be developed, especially for patients who achieve a sustained virologic response. In the current study, we show that a DNA vaccine (GLS-6150) was safe and increased HCV-specific T cell responses. A clinical trial is underway to test this vaccine in patients with a sustained virologic response following DAA therapy.

Scientific Reports3区 · 综合性期刊

Preclinical evaluation of multi antigenic HCV DNA vaccine for the prevention of Hepatitis C virus infection

3区 · 综合性期刊

ArticleOA

作者: Weiner, David B ; Khan, Amir S ; Cho, Byung Mun ; Rothkopf, Zachary ; Park, Young K ; Cho, Youngran ; Stone, John ; Lee, Hyojin ; Son, Woo-Chan ; Maslow, Joel N ; Yan, Jian ; Jeong, Moonsup ; Oh, Jooyeon ; Shen, Xuefei

AbstractDirect-acting antiviral treatment for hepatitis C virus (HCV) infection is costly and does not protect from re-infection. For human and chimpanzees, recovery from acute HCV infection correlates with host CD4+ and CD8+ T cell responses. DNA plasmids targeting the HCV non-structural antigens NS3, NS4, and NS5, were previously reported to induce robust and sustained T cell responses in mice and primates. These plasmids were combined with a plasmid encoding cytokine IL-28B, together named as VGX-6150. The dose-dependent T cell response and safety of VGX-6150 administered intramuscularly and followed by electroporation was assessed in mice. Immune responses plateaued at 20 μg/dose with IL-28B demonstrating significant immunoadjuvant activity. Mice administered VGX-6150 at 40, 400, and 800 μg given either as a single injection or as 14 injections given bi-weekly over 26 weeks showed no vaccine related changes in any clinical parameter compared to placebo recipients. There was no evidence of VGX-6150 accumulation at the injection site or in any organ 1 month following the 14th vaccination. Based on these studies, the approximate lethal dose (ALD) exceeds 800 μg/dose and the NOAEL was 800 μg/dose in mouse. In conclusion, VGX-6150 appears safe and a promising preventive vaccine candidate for HCV infection.

项与 INO-8000 相关的新闻（医药）

2023-06-13

·drugs

How Do You Get Hepatitis C? Here’s What to Know

WEDNESDAY, June 14, 2023 -- Hepatitis C is a viral infection of the liver no one wants to catch, so knowing how that can happen can be critical. The American Liver Foundation estimates that it affects about 2.7 million people in the United States today. To help you protect yourself against this virus, liver experts describe how you get hepatitis C, if it’s curable and how contagious it is. They will also explain if there’s a hepatitis C vaccine, and what medications are used to treat this viral infection. How do you get hepatitis C? According to the U.S. Centers for Disease Control and Prevention , hepatitis C transmission occurs when you come into contact with the blood of someone who is infected. This can happen through: Sharing of drug needles or other injection materials Birth: approximately 6% of children born to infected mothers are also infected Tattoos and piercings, especially from unlicensed and unregulated establishments Sex with someone infected with the virus, which is reported more among men who have sex with other men Sharing medical and other items, such as glucose monitors and razors that have infected blood on them Health care worker exposure to blood-borne infections Organ transplants and blood transfusions “Before 1993, a blood transfusion was a common way to get hepatitis C, but now blood transfusion is safe because we check the blood,” explained Dr. Melissa Jenkins , chief of the division of infectious diseases at MetroHealth, in Cleveland, Ohio. A research article published recently in the journal Pathogens noted that the opioid epidemic and less access to health care have also fueled new hepatitis C cases. Incidents of hepatitis C infections increased by 15% between 2019 and 2020 for acute cases, according to the CDC . Is hepatitis C contagious? The New York State Department of Health says that hepatitis C is typically contagious for at least a week or more before symptoms appear, and remains so “indefinitely” afterward for people with chronic hepatitis. Anyone who tests positive for the virus is considered contagious. Dr. Nancy Reau , hepatology section chief at Rush University Medical Center in Chicago, explained in an American Liver Foundation video that “everyday contact to someone with hepatitis C very, very rarely will lead to infection. So, you should not be afraid of your relatives or loved ones who have hepatitis C.” But, Reau added, “Just be careful with anything that might have been exposed to someone else’s blood or body products.” Is hepatitis C curable? The CDC says the cure rate is over 90% for anyone who is treated for hepatitis C with antiviral medications. “For people who are treated, we check a hepatitis C level 12 weeks or more after the last dose of medicine," Jenkins explained. "If the hepatitis C virus level [viral load] is negative, also known as undetectable, then the patient has a sustained virologic response [SVR]. This is considered a cure.” She added that “people who have cirrhosis prior to treatment still need to see a liver doctor because they are still at risk for liver cancer or complications of cirrhosis, but the risk is much lower after the hepatitis C is gone.” Is there a hepatitis C vaccine? There is no hepatitis C vaccine. According to the Pathogens article, the virus has the genetic ability to make various mutations that are somewhat different from each other, making it challenging to develop an effective vaccine. The American Liver Foundation notes that hepatitis C symptoms don’t often show up until after liver damage has already occurred. In fact, up to 75% of people with the virus don’t know they have it. About 75% to 85% of people who are infected will end up with chronic hepatitis C. “If left untreated, hepatitis C can lead to cirrhosis of the liver and liver cancer,” Jenkins said. “Once cirrhosis develops, it is irreversible.” That’s why the CDC recommends getting a hepatitis C blood test once when you turn 18, and on a regular basis if you have certain risk factors for getting the virus. This helps ensure that treatment can start as soon as possible. “For the last decade, we have had incredibly easy-to-use all-pill therapy [for hepatitis],” Reau explained. “So, the medications are given for between 8 weeks and 12 weeks for almost everybody. They have cure rates of nearly 100% … the medications are incredibly safe and very well-tolerated.” Posted June 2023

2023-06-12

·drugs

There's No Hepatitis C Vaccine, But You Can Still Prevent Infection

MONDAY, June 12, 2023 -- Hepatitis C can ruin your liver, and there's no vaccine to prevent it, but you can take steps to lower your chances of infection. According to the U.S. Centers for Disease Control and Prevention , over 2 million U.S. adults are infected with hepatitis C. The virus strikes the liver and is one of the leading causes of liver transplantation in the United States. When first exposed to the virus, it can remain undetected and cause harm without the individual knowing they are infected. Hepatitis C can result in liver scarring, cancer and death. While there are vaccines for hepatitis A and hepatitis B, viruses that also affect the liver, there is no vaccine for hepatitis C. Here, you will find information about how you can protect yourself against this disease. Is there a vaccine for hepatitis C? Dr. Stacey Rizza answers this question in an article for the Mayo Clinic : “The hepatitis C virus is more variable than hepatitis A and hepatitis B viruses. Hepatitis C occurs in at least seven genetically distinct forms (genotypes) with multiple subtypes. About 60 subtypes have been identified. Different genotypes cause infections in different parts of the world. A global vaccine would have to protect against all variants of the virus.” Another issue with developing the vaccine is the ethical costs and concerns with an animal model that would be used to test the vaccine. Those ethical costs are weighed against the fact that there are antiviral medications that can cure hepatitis C for 95% of patients. Rizza also noted there is an ongoing therapeutic vaccine trial. This vaccine would help people with chronic hepatitis C by bolstering the body's immune response to fight the infection. Hepatitis C prevention The hepatitis C virus is transmitted through exposure to blood from an infected person. According to the CDC , this often occurs from sharing needles, syringes or any other equipment used to prepare and inject drugs. The Veterans Administration recommends taking the following measures to prevent exposure to hepatitis C: Drugs If you use drugs, speak with your provider about treatment to stop using drugs or available harm reduction in your area. If you are unable to stop using drugs: Don’t share any equipment used to prepare or inject drugs, including syringes, needles, filters, water, water containers, cotton or ties Use brand-new or clean needles every time. Do not borrow needles or equipment. Get your needles from a pharmacy or needle exchange program If you must reuse equipment, mark yours for easy identification Use an extra sterile syringe for splitting drugs If you must share a syringe, clean it with bleach and sterile water Snorting drugs can cause bleeding inside your nose, do not share snorting straws Smoking drugs from a pipe can expose you to blood from cracks or burns on lips, so do not share a pipe or use your own rubber stem Sex Practice safe sex, use a condom, dental dam or other latex barrier, and avoid rough sex Receptive anal sex is the riskiest behavior for hepatitis C infection Having a sexually transmitted infection places you at greater risk of hepatitis C infection; ensure you are tested and treated, including receiving vaccines for hepatitis A and hepatitis B Tattoos and piercings Only get tattooed or pierced in regulated studios that display certificates from the state they are located Make sure the tattoo artists are licensed Needles and ink pots should be single-use, and artists should wear latex gloves Prison tattoos and piercings or those done by friends place you at a greater risk If you suspect you may have been exposed or have symptoms of this virus, seek medical care. According to the Mayo Clinic , symptoms include fatigue, nausea, yellowing of the skin, weight loss, confusion, swelling and itchy skin, among others. The Veterans Administration lists the following free resources: Free, fast, and confidential hepatitis C testing from the CDC Drug treatment centers , or 1-800-662-HELP (4357) Needle exchange programs Note: This list may not contain all community programs. Ask your provider if you need help finding a location close to you Protecting yourself and others when using drugs Instructions for cleaning injection equipment Posted June 2023

疫苗

2023-06-12

·drugs

Is There a Cure for Hepatitis C Infection?

MONDAY, June 12, 2023 -- Hepatitis C is a serious viral infection that can damage your liver over time, but is there a cure for this insidious disease? Over 2 million adults in the United States are infected with hepatitis C, according to the U.S. Centers for Disease Control and Prevention . This virus attacks the liver, often silently, in the early stages of the disease. Untreated, hepatitis C can lead to liver scarring, liver cancer and death. It is one of the leading causes of liver transplants in the United States. Fortunately, this potentially deadly disease is curable. How is hepatitis C curable? There have been significant advances in the treatment of hepatitis C. According to the Mayo Clinic , “direct-acting” antiviral medications successfully treat the virus. These treatments have been shown to decrease treatment time with fewer side effects. The exact drugs and treatment plan depends on the hepatitis C genotype, existing liver damage and your medical history. It is recommended to retest for the virus 12 to 24 weeks after treatment, to see if the medication was effective. The World Health Organization reports that “antiviral medicines can cure more than 95% of persons with hepatitis C infection, but access to diagnosis and treatment is low.” It is essential to know that you can be reinfected with hepatitis C after you are cured. Because you can get hepatitis C again once you have cleared the virus, those who have at-risk behaviors should be tested yearly for infection, the CDC says. Is there a hepatitis C vaccine? Hepatitis A and hepatitis B have vaccines available; however, hepatitis C does not. Dr. Stacey Rizza explains why in an article for the Mayo Clinic . “The hepatitis C virus is more variable than hepatitis A and hepatitis B viruses. Hepatitis C occurs in at least seven genetically distinct forms (genotypes) with multiple subtypes," she explained. "About 60 subtypes have been identified. Different genotypes cause infections in different parts of the world. A global vaccine would have to protect against all variants of the virus.” Ethical costs and concerns also exist with using an animal model to develop such a vaccine. Those costs and considerations are weighed against the fact that hepatitis C is curable. Hepatitis C prevention The hepatitis C virus is transmitted through exposure to blood from an infected person. According to the CDC , this often occurs from sharing needles, syringes or any other equipment used to prepare and inject drugs. The Veterans Administration recommends taking the following measures to prevent exposure to hepatitis C: Drugs If you use drugs, speak with your provider about treatment to stop using drugs or available harm reduction in your area. If you are unable to stop using drugs: Don’t share any equipment used to prepare or inject drugs, including syringes, needles, filters, water, water containers, cotton or ties Use brand-new or clean needles every time. Do not borrow needles or equipment. Get your needles from a pharmacy or needle exchange program If you must reuse equipment, mark yours for easy identification Use an extra sterile syringe for splitting drugs If you must share a syringe, clean it with bleach and sterile water Snorting drugs can cause bleeding inside your nose, do not share snorting straws Smoking drugs from a pipe can expose you to blood from cracks or burns on lips, so do not share a pipe or use your own rubber stem Sex Practice safe sex, use a condom, dental dam or other latex barrier, and avoid rough sex Receptive anal sex is the riskiest behavior for hepatitis C infection Having a sexually transmitted infection places you at greater risk of hepatitis C infection; ensure you are tested and treated, including receiving vaccines for hepatitis A and hepatitis B Tattoos and piercings Only get tattooed or pierced in regulated studios that display certificates from the state they are located Make sure the tattoo artists are licensed Needles and ink pots should be single-use, and artists should wear latex gloves Prison tattoos and piercings or those done by friends place you at a greater risk In addition, do not share razors, toothbrushes, toothpicks or nail clippers; these can all harbor the vaccine. And only get injections from a licensed professional who uses clean syringes. If you suspect you may have been exposed or have symptoms of this virus, seek medical care. According to the Mayo Clinic , symptoms include fatigue, nausea, yellowing of the skin, weight loss, confusion, swelling and itchy skin, among others. The Veterans Administration lists the following free resources: Free, fast, and confidential hepatitis C testing from the CDC Drug treatment centers , or 1-800-662-HELP (4357) Needle exchange programs Note: This list may not contain all community programs. Ask your provider if you need help finding a location close to you Protecting yourself and others when using drugs Instructions for cleaning injection equipment Posted June 2023

100 项与 INO-8000 相关的药物交易

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研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
慢性丙型肝炎	临床2期	韩国	GeneOne Life Science, Inc.	2014-01-01
丙型肝炎	临床2期	-	Inovio Pharmaceuticals, Inc.	-
丙型肝炎	临床2期	-	GeneOne Life Science, Inc.	-
丙型肝炎	临床2期	-	University of Pennsylvania	-
丙型肝炎	临床2期	-	Mayo Clinic	-
慢性丙型肝炎	药物发现	韩国	Inovio Pharmaceuticals, Inc.	2014-01-01