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Novel assay to monitor Tacrolimus levels at the point of care

在护理点监测他克莫司水平的新方法

基本信息

批准号：
10203792
负责人：
Martyn Darby
金额：
$ 73.5万
依托单位：
AFFINERGY, LLC
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-06-15 至 2023-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10203792
关键词：
Address Affinity Antibiotics Appointment Binding Biological Biological Assay Blood Blood specimen Characteristics Clinic Clinical Complex Detection Development Dose Drug Kinetics Early identification Evaluation Financial Hardship Freezing Graft Rejection Guidelines Healthcare Systems Immunosuppression Immunosuppressive Agents Institutes Label Laboratories Libraries Life Liquid substance Macrolides Maintenance Measurement Measures Medication Management Methodology Methods Monitor Organ Transplantation Outpatients Patient Appointment Patient Noncompliance Patients Peptides Performance Pharmaceutical Preparations Phase Production Provider Reader Reagent Regimen Reproducibility Risk Running Sampling Ships Solid Specificity Specimen Tacrolimus Tacrolimus Binding Proteins Testing Therapeutic Toxic effect Transplant Recipients United States Validation Visit Whole Blood base cross reactivity design detection limit dosage follow-up graft failure improved large scale production lateral flow assay lot production nanomolar novel performance tests point of care point-of-care detection prevent prototype rapid detection receptor scale up stability testing verification and validation

项目摘要

SUMMARY/ABSTRACT In 2016, over 33,000 organ transplants were performed in the United States, an increase of 20% over the past 5 years. Organ transplantation requires lifelong immunosuppression to prevent rejection of the transplant. Tacrolimus, a macrolide antibiotic, is one of the most effective immunosuppressants, with >90% of solid organ transplant recipients receiving it as part of their maintenance immunosuppression. Tacrolimus has a narrow therapeutic window, with sub-therapeutic levels putting patients at risk for rejection and supra-therapeutic levels leading to toxicity. In addition to significant pharmacokinetic variability, it is also estimated that >25% of patients are non-adherent to their immunosuppressant regimen, significantly increasing graft rejection and failure rates and increasing the financial burden on the US healthcare system. Because transplant recipients require a lifetime of immunosuppression, any methods that facilitate improved dosing and rapid detection of non-adherence are of great clinical utility. Because tacrolimus levels cannot be ascertained at the point of care, detection of non-therapeutic levels in the outpatient setting is challenging. Patients must either attend a separate lab appointment ahead of their routine follow-up visits or they have levels drawn on the day of their visit. In the former, an extra burden is placed on the patient to attend an additional appointment while the latter precludes analysis of levels prior to the patient’s appointment. Delays in medication management or identification of patient non-compliance place the patient at risk for graft rejection (sub-therapeutic levels) or drug-associated toxicities (supra-therapeutic levels). To address this technical hurdle, Affinergy plans to develop a point-of-care lateral flow assay that will enable frequent, accurate and affordable monitoring of tacrolimus levels. We have already generated a proprietary capture reagent and identified several detection reagent candidates that bind with nanomolar affinity to tacrolimus. At the conclusion of Phase I, we will have a prototype lateral flow assay with established limits of quantitation. In Phase II, we will scale up production of our assay, optimize performance characteristics, establish storage conditions, determine stability and evaluate our assay using transplant recipient blood specimens. Successful completion of this project will lead to improved long-term maintenance of patients receiving tacrolimus for immunosuppression and ease the burden on both patients and providers.

摘要/文摘