Low Dose Oral Carbon Monoxide Therapeutic for Virus-Induced Lung Injury

低剂量口服一氧化碳治疗病毒引起的肺损伤

基本信息

批准号：
10682510
负责人：
Edward Gomperts
金额：
$ 29.99万
依托单位：
HILLHURST BIOPHARMACEUTICALS, INC.
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-08-11 至 2024-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10682510
关键词：
2019-nCoV Accidents Acute Acute Lung Injury Acute Respiratory Distress Syndrome Animal Model Animals Antiviral Agents Award Binding Biological Availability COVID-19 COVID-19 impact COVID-19 patient COVID-19 treatment Canis familiaris Carbon Monoxide Cells Chronic Chronic Obstructive Pulmonary Disease Clinical Research Clinical Trials Data Development Dexamethasone Dose Economics Experimental Animal Model Experimental Models Formulation Gases Goals Hemoglobin Hemoglobin concentration result Human Immune response Infection Inflammation Inflammatory Inflammatory Response Influenza Influenza A Virus, H1N1 Subtype Influenza A virus Inhalation Inhalation Exposure Injury Innate Immune Response Intensive Care Intensive Care Units Kinetics Laboratories Life Liquid substance Literature Lung Lung diseases Lung infections Mesocricetus auratus Methods Modality Modeling Morbidity - disease rate Mus Oral Pathology Patients Persons Pharmaceutical Preparations Phase Phase I Clinical Trials Phase II Clinical Trials Physiological Pulmonary Inflammation Rattus Research Research Personnel Research Support Respiratory physiology Risk SARS-CoV-2 infection Safety Seasons Secure Sickle Cell Anemia Small Business Innovation Research Grant Taxes Testing Therapeutic Therapeutic Uses Time Tissue Model Toxic effect Toxicology Translations Treatment Efficacy United States Vaccination Viral Viral Load result Viral Respiratory Tract Infection Virus Virus Diseases Writing antiviral drug development clinically relevant experience healthy volunteer hospital care human subject immunoregulation improved improved outcome in vivo innovation lung injury mortality novel novel strategies novel therapeutics pandemic disease phase 2 study pre-Investigational New Drug meeting pre-clinical preclinical efficacy preclinical study prevent research clinical testing therapeutic development therapeutically effective treatment strategy viral pandemic

项目摘要

PROJECT SUMMARY There is an urgent need for the development of new approaches to treat patients suffering from pulmonary injury from viral infections, as demonstrated by the severe impact of COVID-19, which is a global pandemic that, at the time of writing, is estimated have impacted approximately 50 million people in the United States, leading to morbidity, substantial hospital and intensive care utilization, and mortality. In multiple preclinical studies, we and others have defined the therapeutic potential of low dose exogenous carbon monoxide (CO) in acute lung injury, including in virus-induced pulmonary injury, by reducing inflammation and promoting viral clearance. To date, inhaled CO gas (iCO) and CO bound to carrier molecules (CORMs) have been the modalities of choice in the majority of animal and in all the clinical studies, and the safety and tolerability of CO has been demonstrated in 23 successful Phase 1 and 2 clinical studies, including in patients with pulmonary conditions such as ARDS and COPD. However, iCO and CORMS are not expected to be pharmaceutically acceptable and viable therapeutic options in COVID patients due to, for iCO, the risk of accidental inhalation exposure from the presence of compressed CO gas cylinders and imprecise dosing, especially in COVID-19 patients that have limited and variable respiratory function, and, for CORMs, problematic release kinetics and toxicological concerns with carrier molecules. The objective of the proposed project is to investigate HBI-002, a novel oral low dose CO drug product that enables the use of low dose CO in viral infections associated with acute pulmonary injury, such as COVID-19. HBI-002 is an oral liquid drug product containing CO. An IND is in place for HBI-002, with a Phase 1 clinical trial in healthy volunteers planned in 2022. The next step in development is to demonstrate that HBI-002 is effective in clinically relevant animal models of viral acute lung injury as has been shown with other forms of CO and to better understand the potential mechanism(s) of action. Based upon the substantial literature of CO in acute lung injury and our and others findings in virus-induced lung injury, our central hypothesis that will be tested in this project is: HBI-002 modulates the immune response to regulate inflammation and improve viral clearance in experimental models of virally induced lung injury sufficiently to warrant a Phase 2 clinical trial.

项目摘要迫切需要开发新方法来治疗肺部损伤的患者从病毒感染中，由于19 Covid-19的严重影响证明了这一点，这是一个全球性的大流行，在据估计，撰写时间的时间已影响美国约5000万人，导致发病率，大量医院和重症监护术以及死亡率。在多个临床前研究中，我们和其他人则定义了急性肺损伤中低剂量外源碳（CO）的治疗潜力，包括病毒诱导的肺损伤，通过减少炎症和促进病毒清除率。迄今在大多数动物和所有临床研究中，已经证明了CO的安全性和耐受性在23阶段和2阶段和2次临床研究中，包括在肺部疾病（例如ARDS）的患者中和COPD。但是，ICO和CORM不预计是可以接受且可行的由于ICO而导致的相互vid患者的治疗选择存在压缩的CO气缸和不精确的给药有限和可变的呼吸功能，对于Corms，有问题的释放动力学和毒理学对载体分子的关注。拟议项目的目的是研究HBI-002，这是一种新颖的口头低点剂量CO药物产物可以在与急性肺部相关的病毒感染中使用低剂量CO 伤害，例如19岁。 HBI-002是含有Co的口服液体药物。在计划于2022年计划的健康志愿者中。开发的下一步是证明HBI-002是有效的在临床相关的病毒急性肺损伤的动物模型中，其他形式的CO和TO 更好地了解动作的潜在机制。基于急性肺中CO的大量文献受伤以及我们和其他人在病毒引起的肺损伤方面的发现，我们将在此测试的中心假设项目是：HBI-002调节免疫反应以调节炎症并改善病毒清除率在病毒诱导的肺损伤的实验模型中，足以保证2期临床试验。