Safety “Clinical Trial” of the Cardiac Liability of COVID19 Polytherapy
Grant Award Details
Grant Number:
DISC2P-11946
Investigator(s):
Disease Focus:
Human Stem Cell Use:
Award Value:
$224,500
Status:
Closed
Progress Reports
Reporting Period:
Year 1
Grant Application Details
Application Title:
Safety “Clinical Trial” of the Cardiac Liability of COVID19 Polytherapy
Public Abstract:
Research Objective
Validating the cardiac MPS as tool to predict cardiac toxicity, including modeling drug-drug interaction of polytherapy for the treatment of SARS-CoV-2.
Impact
Our cardiac MPS will identify polytherapy combinations that have cardiac liability versus those that do not, which will lead to substantial cost and time savings to bring the safe drugs to patients.
Major Proposed Activities
["Milestone 1 – Conduct dose escalation studies of Epclusa (velpatasvir/sofosbuvir) and Zepatier (elbasvir/grazoprevir), and remdesivir to assess cardiac liabilities. [1 hiPSC-CM line]", "Milestone 2 – De-risk COVID-19 drug development with respect to cardiac effects of chronic drug treatment, modeling diversity in clinical trial protocols. [6 hiPSC-CM lines]"]
Validating the cardiac MPS as tool to predict cardiac toxicity, including modeling drug-drug interaction of polytherapy for the treatment of SARS-CoV-2.
Impact
Our cardiac MPS will identify polytherapy combinations that have cardiac liability versus those that do not, which will lead to substantial cost and time savings to bring the safe drugs to patients.
Major Proposed Activities
["Milestone 1 – Conduct dose escalation studies of Epclusa (velpatasvir/sofosbuvir) and Zepatier (elbasvir/grazoprevir), and remdesivir to assess cardiac liabilities. [1 hiPSC-CM line]", "Milestone 2 – De-risk COVID-19 drug development with respect to cardiac effects of chronic drug treatment, modeling diversity in clinical trial protocols. [6 hiPSC-CM lines]"]
Statement of Benefit to California:
Outcomes from this proposal will more effectively inform clinical trial design, and determine if extensive ECG monitoring in early clinical trials is necessary for patients with severe COVID-19 and risks for cardiac liability. Moreover, our data will guide clinical management by predicting which drugs need to be avoided or dose adjusted to prevent DDI. Importantly, our work has potential for substantial time and cost savings to bring COVID-19 polytherapies to Californian patients.
Publications
- Front Pharmacol (2021): Heart Muscle Microphysiological System for Cardiac Liability Prediction of Repurposed COVID-19 Therapeutics. (PubMed: 34421592)
- Clin Transl Sci (2021): In vitro safety “clinical trial” of the cardiac liability of drug polytherapy. (PubMed: 33786981)
- bioRxiv (2020): In Vitro Safety “Clinical Trial” of the Cardiac Liability of Hydroxychloroquine and Azithromycin as COVID19 Polytherapy. (PubMed: 33398282)