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标题: GI-13020 [打印本页]

作者: 瑞雪丰年 时间: 2013-2-16 05:37 标题: GI-13020

Gilead的治疗性乙肝疫苗启动一期临床实验

作者: 瑞雪丰年 时间: 2013-2-16 07:07

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January 28, 2013
LOUISVILLE, Colo., Jan. 28, 2013 – GlobeImmune, Inc., today announced the initiation of a Phase 1a clinical trial to investigate the safety and immunogenicity of GI-13020 in healthy volunteers.  The GI-13020 Tarmogen®, which GlobeImmune is developing in collaboration with Gilead Sciences, Inc., consists of whole, heat-killed, recombinant S. cerevisiae yeast genetically modified to express hepatitis B (HBV) antigens.  This study is being conducted under an Investigational New Drug application (IND) that was filed with the U.S. Food and Drug Administration in December 2012. As a result of successfully filing the IND, GlobeImmune received a milestone payment from Gilead.

The GI-13020-01 Phase 1a clinical trial is a randomized, open-label, dose escalation trial assessing the safety, tolerability and immunogenicity of various doses of GI-13020 in healthy adults.  This study is designed to enroll 48 evaluable subjects at a single U.S.center.

“While approved anti-viral drugs have been shown to effectively suppress replication of the hepatitis B virus, they rarely result in cures and must be taken indefinitely,” said David Apelian, M.D., Ph.D., Chief Medical Officer at GlobeImmune. “GI-13020 is designed to activate an antigen-specific immune response against HBV, and our development strategy will be to combine GI-13020 with direct-acting antiviral medicines to determine if the combination can increase rates of surface antigen seroconversion, thereby leading to a cure for infected patients.”

HBV infection is the most common form of chronic viral hepatitis in the world.  Approximately 350 million people worldwide are chronic carriers of HBV, resulting in more than 620,000 deaths annually from liver-related diseases. In theUnited States, chronic HBV infection affects up to 1.4 million people.  Current treatment for HBV includes once-daily oral antiviral therapy medicines to suppress virus replication. These antiviral products have been effective in controlling the disease but generally do not result in a long-term cure, thus requiring chronic suppressive therapy.

作者: StephenW 时间: 2013-2-16 09:32

本帖最后由 StephenW 于 2013-2-16 09:32 编辑

Purpose

This trial will be test the safety, tolerability, and immunogenicity of GI-13020 in various doses and dosing regimens in healthy adults at one center in the US. Subjects will be enrolled into 3 arms using a dose escalation scheme and randomized into one of two dosing regimen cohorts. There will be 10 subjects per arm/cohort (total of 60 subjects to achieve 48 evaluable subjects enrolled), with study completion in 9-12 months.

目的

该试验将测试的安全性，耐受性和免疫原性不同剂量和给药方案，在一个健康的成年人中心在美国GI-13020。主题将被登记为3个武器，使用剂量升级计划，并随机分成两种给药方案组群之一。将有10个科目，每臂/队列（共60名受试者达到48评估的科目参加），在9-12个月的研究结束。

Condition	Intervention	Phase
Healthy Volunteers	Biological: GI-13020	Phase 1

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A Randomized, Open-Label, Multi-Arm, Dose Escalation, Phase 1a Trial Assessing the Safety, Tolerability, and Immunogenicity of GI-13020; an Inactivated Recombinant Saccharomyces Cerevisiae Expressing Hepatitis B Virus X, Surface and Core Antigens, at Various Dose Levels and Regimens in Healthy Adults.

  Further study details as provided by GlobeImmune:

            Primary Outcome Measures:

Safety of GI-13020 at various doses [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]Frequency of serious adverse events Frequency and severity of common non-serious adverse events Frequency of discontinuations of therapy due to adverse events Common laboratory assessments (chemistry, hematology, urinalysis) Dose Limiting Toxicities

Secondary Outcome Measures:

Immunogenicity of various doses and dosing regimens of GI-13020 [ Time Frame: 6 months ] [ Designated as safety issue: No ]Frequency and magnitude of antigen specific immune responses by ELISpot assay for cytokine production, to include IFNγ Frequency and magnitude of antigen specific immune responses by lymphocyte proliferation assay (LPA) Frequency and magnitude of anti-Saccharomyces cerevisiae antibody (ASCA) responses Pentamer staining for HBV specific T cells Frequency of regulatory T cells (Treg) responses

Estimated Enrollment:	60
Study Start Date:	January 2013
Estimated Study Completion Date:	October 2013
Estimated Primary Completion Date:	July 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: GI-13020 at 10YU10YU of GI-13020 given either weekly or monthly	Biological: GI-13020GI-13020 is a recombinant yeast-based biological product engineered to express HBV antigens. The product is a heat-killed yeast (S. cerevisiae) containing a chimera of HBV X, Score, and Core antigens.
Experimental: GI-13020 at 40YU40YU of GI-13020 given either weekly or monthly	Biological: GI-13020GI-13020 is a recombinant yeast-based biological product engineered to express HBV antigens. The product is a heat-killed yeast (S. cerevisiae) containing a chimera of HBV X, Score, and Core antigens.
Experimental: GI-13020 at 80YU80YU of GI-13020 given either weekly or monthly	Biological: GI-13020GI-13020 is a recombinant yeast-based biological product engineered to express HBV antigens. The product is a heat-killed yeast (S. cerevisiae) containing a chimera of HBV X, Score, and Core antigens.

Detailed Description:

HBV specific T cell responses have been shown to have a positive association with infection status in patients with chronic HBV, with the weakest T cell responses in patients with untreated chronic active infection and the strongest T cell responses in patients who have achieved seroconversion or cure (4). We have generated a Tarmogen expressing well conserved regions of the HBV X, S, and core antigens (GI-13020). GI-13020 is immunogenic in murine models and has also been used to stimulate human immune cell samples ex vivo to elicit HBV specific T cell responses which could predict the immune responses in patients dosed with GI-13020. GI-13020 will be evaluated in this healthy volunteer study to assess its safety, tolerability, and ability to elicit HBV specific T cell responses. In the future GI-13020 could be used in combination with HBV antivirals, such as tenofovir disoproxil fumarate, in an attempt to improve HBsAg seroconversion (cure) rates in patients with chronic HBV infection.

详细说明：

HBV特异性T细胞反应已被证明有慢性乙肝患者的感染状况呈正相关，与最弱的T细胞反应，患者未经治疗的慢性活动性感染和最强的T细胞反应，谁取得了血清学转换或治愈的患者（ 4）。我们已经生成了Tarmogen表达HBV X，S，和核心抗原（GI-13020）以及保守区域。 GI-13020的小鼠模型中是免疫原性的，并也被用于刺激人体免疫细胞样品体外引起HBV特异性T细胞的反应，可以预测GI-13020给药患者的免疫反应。 GI-13020将这种健康志愿者研究中进行评估，以评估其安全性，耐受性，并引起HBV特异性T细胞反应的能力。在未来的GI-13020可以组合使用与HBV的抗病毒剂，如富马酸替诺福韦酯，以尝试提高HBsAg的血清转化（固化）在慢性HBV感染的患者评分。

作者: 咬牙硬挺 时间: 2013-2-16 14:02

好消息啊

作者: 海上明月光 时间: 2013-2-16 14:54

这个和国内的有啥区别啊？

作者: StephenW 时间: 2013-2-16 15:36

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基本机制是很难理解的, 是基于树突状(dendritic)细胞.
看解释:http://www.globeimmune.com/platform/technology/

最大的区别是Gilead公司是其背后支持的.

作者: 海上明月光 时间: 2013-2-16 15:42

国内闻玉梅的也是基于树突状(dendritic)细胞吗？

她失败了，这个也很可能失败？

作者: StephenW 时间: 2013-2-16 15:56

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国内闻玉梅的也是基于树突状(dendritic)细胞吗？YIC依赖树突状细胞。树突状细胞是APC（抗原呈递细胞）.

在GI-13020, 树突状(dendritic)细胞,也充当如被乙肝病毒感染 (只是我的理解，可能是错的).

作者: 海上明月光 时间: 2013-2-16 16:02

谢谢
YIC是什么啊？是闻玉梅研究的依赖“树突状细胞”的其他细胞吗？
GI-13020和YIC没关系，只管树突状细胞？

作者: StephenW 时间: 2013-2-17 03:39

本帖最后由 StephenW 于 2013-2-17 03:44 编辑

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IC是什么啊？是闻玉梅研究的依赖“树突状细胞”的其他细胞吗？
GI-13020和YIC没关系，只管树突状细胞?

闻玉梅教授的疫苗被称为YIC -Yeast Immuno Complex -酵母(yeast)免疫复合物-HBsAg和HBsAb的复合物. HBsAg和HBsAb来自基因工程(genetic engineered)过的酵母(yeast)细胞. YIC没有DNA,没有酵母(yeast)细胞, 只有HBsAg和HBsAb.

GI-13020 包含加热杀死的基因工程(genetic engineered)过的酵母(yeast)细胞,有DNA.也有HBV抗原.

因为有DNA材料，GI-13020影响
dendritic树突状细胞，两种不同的方式.

作者: 海上明月光 时间: 2013-2-17 07:48

哦，谢谢StephenW！

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