Developmental Clinical Studies - A Phase I study of a novel peptide fusion inhibitor for the treatment of chronic HIV infection

开发性临床研究——用于治疗慢性 HIV 感染的新型肽融合抑制剂的 I 期研究

• 批准号: MR/J002178/1
• 负责人: Alan Winston
• 金额: $ 103.42万
• 依托单位: Imperial College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2013
• 资助国家: 英国
• 起止时间: 2013 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FJ002178%2F1
• 关键词: Developmental; Clinical; Studies; Phase; study

With the development of effective antiretroviral (anti-HIV) therapy over the last two decades, in resource rich countries, individuals with HIV infection can live for many years and as a consequence of this success, are now developing age related medical problems as seen in all ageing populations.Dealing with an ageing HIV infected population is therefore a new medical phenomenon and poses new challenges including managing interactions between medication to treat HIV infection and medication to treat other medical conditions. This is problematic as the vast majority of current anti-HIV therapies are prone to interactions with other medications. Also, many current anti-HIV therapies have side effects which are more problematic in older individuals such as increasing risk of heart attacks or rises in cholesterol. Given these factors, new antiretroviral agents without the propensity to interact with other medication and with improved side effect profiles represent a crucial medical need.We have developed a new antiretroviral drug, currently known as C34-PEG4-Chol, which prevents the HIV virus from entering cells. Although required to be given by injection, C34-PEG4-Chol only requires to be given twice or even once weekly and is likely to have minimal side effects with no interactions with other medicines. To date, C34-PEG4-Chol has been studied in the laboratory and in animal models. We propose to assess the safety and anti-HIV activity of this new agent in subjects with chronic HIV infection for the first time.This proposal brings together scientific and clinical expertise in HIV medicine with the company who have developed C34-PEG4-Chol and the study will be conducted within a registered UK trials unit. This novel antiretroviral agent has the potential to offer a low toxicity, easily administered, antiretroviral agent as part of effective antiretroviral therapy for the future avoiding the treatment limiting toxicities of current licensed agents.

随着有效的抗逆转录病毒药物的发展在过去二十年中，在资源丰富的国家，艾滋病毒感染者可以活很多年，由于这种成功，因此，应对老龄化的艾滋病毒感染人群是一种新的医学现象，并提出了新的挑战，包括管理药物之间的相互作用，治疗艾滋病毒感染和治疗其他疾病的药物。这是一个问题，因为目前绝大多数抗艾滋病毒疗法都容易与其他药物相互作用。此外，目前许多抗艾滋病毒疗法都有副作用，这些副作用在老年人中更成问题，例如增加心脏病发作或胆固醇升高的风险。考虑到这些因素，新的抗逆转录病毒药物没有与其他药物相互作用的倾向，并与改善副作用的概况代表了一个关键的医疗需求。我们已经开发了一种新的抗逆转录病毒药物，目前被称为C34-PEG 4-Chol，它可以防止艾滋病毒进入细胞。虽然需要通过注射给药，但C34-PEG 4-Chol只需要每周给药两次甚至一次，并且可能具有最小的副作用，与其他药物没有相互作用。迄今为止，C34-PEG 4-Chol已在实验室和动物模型中进行了研究。我们建议首次评估这种新药物在慢性HIV感染者中的安全性和抗HIV活性。这项建议将HIV药物的科学和临床专业知识与开发C34-PEG 4-Chol的公司结合在一起，这项研究将在英国注册的试验单位内进行。这种新型抗逆转录病毒药物有可能提供一种低毒性、易于给药的抗逆转录病毒药物，作为未来有效抗逆转录病毒治疗的一部分，避免目前许可药物的治疗限制毒性。

项目成果

Developing a Bayesian adaptive design for a phase I clinical trial: a case study for a novel HIV treatment.

• DOI: 10.1002/sim.7169
• 发表时间: 2017-02-28
• 期刊: Statistics in medicine
• 影响因子: 2
• 作者: Mason AJ;Gonzalez-Maffe J;Quinn K;Doyle N;Legg K;Norsworthy P;Trevelion R;Winston A;Ashby D
• 通讯作者: Ashby D

Pharmacokinetic profile and safety of 150 mg of maraviroc dosed with 800/100 mg of darunavir/ritonavir all once daily, with and without nucleoside analogues, in HIV-infected subjects.

在 HIV 感染受试者中，每日一次服用 150 mg 马拉韦罗与 800/100 mg 地芦那韦/利托那韦（含或不含核苷类似物）的药代动力学特征和安全性。

• DOI: 10.1093/jac/dkt006
• 发表时间: 2013
• 期刊: The Journal of antimicrobial chemotherapy
• 作者: Mora-Peris B