TUTI-16(TUTI-16) - 药物靶点：HIV-1 tat_专利_临床

概要

基本信息

药物类型

治疗性疫苗

别名

靶点

HIV-1 tat

作用机制

Tat (HIV)抑制剂(人类免疫缺陷病毒tat基因产品抑制剂)

治疗领域

免疫系统疾病感染泌尿生殖系统疾病

在研适应症-

非在研适应症

HIV感染

原研机构

Thymon, LLC

在研机构-

非在研机构

Thymon, LLC

最高研发阶段无进展临床2期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

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关联

3

项与 TUTI-16 相关的临床试验

NCT01335191 / Completed临床1/2期

Clinical Study of TUTI-16 in Asymptomatic, HIV-1 Infected Subjects Effectively Controlled by Antiretroviral Therapy and the Effects on Viral Load During a Structured Treatment Interruption

This protocol represents the third in human study of TUTI-16, and is being conducted to gather additional safety and human immunogenicity (anti-HIV-1 Tat titers) data of subcutaneously administered TUTI-16.

开始日期2011-06-01

申办/合作机构

Thymon, LLC

NCT01144026 / Completed临床1/2期

Phase I/IIA Clinical Study of TUTI-16 in HIV-1 Infected and Uninfected Subjects

This protocol represents the second in human study of TUTI-16, and is being conducted to continue to gather safety and human immunogenicity (anti-HIV-1 Tat titers) data of subcutaneously administered TUTI-16.

开始日期2010-09-01

申办/合作机构

Thymon, LLC

NCT00848211 / Completed临床1/2期

Phase I/IIA Clinical Study of TUTI-16 in Asymptomatic HIV-1 Infected Subjects

This protocol represents the first in human study of TUTI-16, and is being conducted to establish the safety and human immunogenicity (anti-HIV-1 Tat titers) of subcutaneously administered TUTI-16. Activity of TUTI-16 will also be determined in minimizing HIV-1 viral loads and sustaining CD4+ T-cell levels.

开始日期2009-02-01

申办/合作机构

Thymon, LLC

100 项与 TUTI-16 相关的临床结果

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100 项与 TUTI-16 相关的转化医学

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100 项与 TUTI-16 相关的专利（医药）

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3

项与 TUTI-16 相关的文献（医药）

2012-10-16·Human Vaccines & Immunotherapeutics3区 · 医学

HIV rebound with current ART appears to be due to infection with new endogenous founder virus and not to resurgence of pre-existing Tat-dependent viremia

3区 · 医学

Article

作者: Mardik Donikyan ; Eve Damiano ; Erik Beckwith ; John Chicca ; Malika Pasha ; Gideon Goldstein

CD4 T cell activation, essential for productive HIV infection, is provided initially in acute HIV infection by innate immune system secretion of activating cytokines. This cytokine response wanes with time and long-term activation of CD4 cells is maintained by HIV Tat protein secreted by HIV infected cells. Structured treatment interruption (STI) in well-controlled antiretroviral-treated (ART) subjects was explored a decade ago with a consensus finding that, in most subjects, HIV levels rebounded within four weeks to pre-ART levels. Based on these observations we initiated a randomized placebo-controlled study of a universal anti-Tat epitope vaccine, TUTI-16, to determine if immunological blockade of Tat would prevent HIV rebound after ART cessation. TUTI-16 immunization was safe, with predominantly mild local and systemic injection-related adverse reactions. TUTI-16 was also immunogenic, with high levels of anti-Tat antibodies compared with levels previously shown to reduce HIV replication in vivo. Of 21 subjects analyzed, 13 (62%) had HIV rebounds vs. 8 (38%) that remained aviremia, but this distribution was not vaccine-related (p = 0.61 log-rank (Mantel-Cox) test), nullifying our hypothesis that anti-Tat antibodies would block rebound of Tat-dependent set-point HIV viremia after ART cessation. Our present findings are consistent with recent molecular findings that rebounding virus following STI is homogeneous and unrelated to previous circulating HIV, suggesting that rebounding HIV represents new founder virus, akin to the original acute HIV infection. We propose, therefore, that STI may have potential as a practical and economical approach to testing the safety and efficacy of candidate prophylactic HIV vaccines.

2012-04-16·Human Vaccines & Immunotherapeutics3区 · 医学

Exploratory clinical studies of a synthetic HIV-1 Tat epitope vaccine in asymptomatic treatment-naïve and antiretroviral-controlled HIV-1 infected subjects plus healthy uninfected subjects

3区 · 医学

Article

作者: Gideon Goldstein ; John J Chicca

TUTI-16 is a synthetic universal HIV-1 Tat epitope vaccine, designed to induce anti-Tat antibodies that block the function of circulating Tat, an HIV encoded protein secreted by HIV-1 infected cells. Circulating Tat activates CD4 T cells, permitting HIV replication and sustained viremia. Safety, immunogenicity and antiretroviral potential of TUTI-16 were explored in a randomized double-blind dose-escalating study in asymptomatic treatment-naïve HIV-1 infected subjects. TUTI-16 was safe, with mild local and systemic injection-related adverse reactions, but the antibody response was barely detectable. Surprisingly, a highly statistically significant reduction of HIV-1 viral load was found in the lowest 30 μg vaccine dose group (p < 0.01) but not at the higher doses. We posited that an anti-Tat antibody response below the limit of detection inhibited HIV viral load at this dose, an effect nullified at higher vaccine doses by activating cytokines induced by adjuvant components in TUTI-16. To clarify this immunogenicity/activation conundrum open label immunogenicity studies were performed in healthy HIV uninfected and aviremic ART-controlled HIV-infected subjects. These established that (1) healthy HIV negative subjects had robust antibody responses, maximal with 1 mg TUTI-16, (2) ART-controlled aviremic HIV infected subjects had similarly robust antibody responses, and (3) adjuvant-induced increases of HIV viral load did not occur in the presence of ART. These studies provided us a basis for the design of a protocol to explore the therapeutic potential of TUTI-16 vaccination to provide drug free control of HIV-1 viremia.

2010-01-01·Vaccine3区 · 医学

A universal anti-HIV-1 Tat epitope vaccine that is fully synthetic and self-adjuvanting

3区 · 医学

Article

作者: John J. Chicca ; Gideon Goldstein

Circulating HIV-1 Tat protein is essential for maintenance of the chronic HIV replication that predicates both HIV transmission and clinical progression to AIDS/death. A synthetic anti-Tat epitope vaccine (TUTI-16) was designed to induce neutralizing antibodies to Tat and, hopefully, provide immunological control of HIV replication. TUTI-16 is composed of (1) a conserved Tat B cell epitope (Tat 4-12), rendered universal by introducing known variant amino acids at variable positions 7, 9 and 12 during solid phase synthesis, (2) a promiscuous T helper sequence and (3) a lipopeptide toll-like receptor 2 (TLR2) agonist. TUTI-16 induced high titer antibodies against all 8 known variants of the Tat epitope.

100 项与 TUTI-16 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
HIV感染	临床3期	美国	Thymon, LLC	2009-02-01

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临床结果

适应症

分期

评价

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT01335191 (THYMON-11001, CTgov)	临床1/2期	HIV感染	27	TUTI-16 (1.0 mg) (TUTI-16 (1.0 mg))	獵製鑰製蓋窪積壓獵襯(衊範選鏇糧蓋窪構醖糧) = 窪蓋願選願鹽壓壓築選鹽醖鏇憲觸淵襯遞獵鏇 (鹹構獵觸夢獵窪築廠築, 製糧餘醖網醖觸鏇範蓋 ~ 艱蓋鹹鑰鹹鏇壓獵鏇膚) 更多	-	2013-02-15
				Placebo (Placebo)	獵製鑰製蓋窪積壓獵襯(衊範選鏇糧蓋窪構醖糧) = 顧願鬱襯糧願衊鹹鹹衊鹽醖鏇憲觸淵襯遞獵鏇 (鹹構獵觸夢獵窪築廠築, 願壓憲衊製範遞鹹壓廠 ~ 積衊淵餘醖繭襯顧獵鬱) 更多
NCT01144026 (THYMON-10001, CTgov)	临床1/2期	HIV感染	15	TUTI-16 (0.2mg) (TUTI-16 (0.2mg))	鑰範構積築廠憲窪鬱範(壓壓繭窪憲廠鏇醖蓋憲) = 膚憲鹽窪鑰艱願積鹽憲憲醖構鬱膚鑰遞簾淵窪 (淵蓋構範夢鑰鏇廠築糧, 鹽淵鏇積築積艱餘鬱蓋 ~ 選繭網窪鹽廠遞餘遞構) 更多	-	2013-01-15
				TUTI-16 (1.0 mg) (TUTI-16 (1.0 mg))	鑰範構積築廠憲窪鬱範(壓壓繭窪憲廠鏇醖蓋憲) = 繭範顧醖窪願繭膚選顧憲醖構鬱膚鑰遞簾淵窪 (淵蓋構範夢鑰鏇廠築糧, 獵鹹壓築網蓋淵憲憲齋 ~ 憲觸餘鏇憲衊艱鹽壓獵) 更多