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Development of TNX-1300 (Double Mutant Cocaine Esterase) for the Treatment of Life-Threatening Cocaine Intoxication

开发 TNX-1300（双突变可卡因酯酶）用于治疗危及生命的可卡因中毒

基本信息

批准号：
10668212
负责人：
GREGORY M SULLIVAN
金额：
$ 201.92万
依托单位：
TONIX PHARMACEUTICALS, 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：
2022-08-01 至 2025-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10668212
关键词：
Accident and Emergency department Acute Address Applications Grants Behavioral Symptoms Biological Assay Blood Butyrylcholinesterase Cardiovascular system Circulation Clinical Clinical Research Cocaine Cocaine Abuse Coupled Development Diagnosis Dose Emergency Care Enzymes Fermentation Freeze Drying Future Goals Health Health care facility Individual Inhalation Injections Insufflation Intervention Intoxication Investigational Drugs Investigational New Drug Application Laboratory Study Life Market Research Marketing Measures Medical Nature Neurologic Neurologic Symptoms Outcome Output Patients Persons Pharmaceutical Preparations Pharmacologic Substance Pharmacotherapy Phase Physicians Plasma Positioning Attribute Preparation Prevalence Process Production Program Development Public Health Publications Recombinants Recreation Risk Running Safety Serious Adverse Event Single-Blind Study Site Supportive care Symptoms Temperature Testing Therapeutic Therapeutic Agents Toxic effect United States United States Food and Drug Administration acute care associated symptom cocaethylene cocaine esterase cocaine self-administration cocaine use commercialization cost design efficacy evaluation emergency settings experience first-in-human healthy volunteer human study individual patient innovation insight intravenous administration intravenous injection manufacturing process meetings mutant norcocaine novel novel therapeutics open label phase 2 study phase 3 study programs randomized trial standard of care thermostability

项目摘要

PROJECT SUMMARY/ABSTRACT In the United States, recreational cocaine use continues to represent a significant public health concern. In 2018, an estimated 5.5 million people recreationally self-administered cocaine by insufflation, inhalation, or injection. Many of these individuals are at risk of succumbing to acute cocaine intoxication, a condition in which life-threatening cardiovascular and neurological symptoms are experienced. The current standard of care consists primarily of supportive acute care directed at the specific symptoms expressed by individual patients. Despite the significant unmet medical need, no pharmacotherapies are approved for treating cocaine toxicity in the acute care setting. The development of a treatment that addresses the root cause of cocaine intoxication (i.e., circulating cocaine and its active metabolites), would allow clinicians to provide a potentially faster and safer intervention in the acute care setting. Furthermore, by directly removing the toxic offending agent from the systemic circulation, such a treatment could more effectively and comprehensively address the multiple medical risks and sequelae of cocaine intoxication. To fulfill this unmet need, Tonix is developing TNX-1300, a mutant recombinant bacterial cocaine esterase (CocE) that has been shown in a pilot Phase 2 clinical laboratory study to metabolize and reduce by ~90% systemic cocaine levels within 2 minutes of a single intravenous administration. In this U01 application, Tonix proposes to advance the TNX-1300 development program via the following specific aims: 1. conduct a Phase 2 proof-of-concept randomized trial of patients presenting to emergency department sites in a state of cocaine intoxication; 2. optimize CMC production of a GMP drug product batch for use in Phase 2 and 3 trials, including a lyophilization cycle; 3. facilitate completion of regulatory milestones, in particular the preparation and execution of an End of Phase 2 meeting with FDA; and 4. a commercialization program with key opinion leader development, target product profile testing, and market research with physicians, payers and patients, to inform the design of a future Phase 3 that will be fully developed and designed in Year 3 of this program. Successfully achieving the milestones outlined in this proposal would substantially advance this novel treatment approach to the stage of Phase 3 pivotal testing requisite for the New Drug Application and marketing approval.

项目总结/文摘