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。
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.
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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。
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