Ignite Creation Date:
2024-05-06 @ 2:31 PM
Last Modification Date:
2024-10-26 @ 1:32 PM
Study NCT ID:
NCT04346277
Status:
NO_LONGER_AVAILABLE
Last Update Posted:
2021-06-21
First Post:
2020-04-13
Brief Title:
Compassionate Use Open-Label Anti-CD14 Treatment in Patients With SARS-CoV-2 COVID-19
Sponsor:
Implicit Bioscience
Organization:
Implicit Bioscience
Study Overview
Official Title:
Compassionate Use Open-Label Anti-CD14 Treatment in Patients With SARS-CoV-2 COVID-19
Status:
NO_LONGER_AVAILABLE
Status Verified Date:
2021-06
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This protocol proposes to use IC14 a recombinant chimeric monoclonal antibody mAb recognizing human CD14 to block CD14-mediated cellular activation in patients early in the development of ARDS The binding of IC14 to human CD14 prevents CD14 from participating in the recognition of PAMPs and DAMPs due to SARS-CoV-2 infection The putative mechanism of action of IC14 in ARDS is blockade of PAMP and DAMP interactions with CD14 thus attenuating the inflammatory cascade that leads to increased endothelial and epithelial permeability and injury resulting in alveolar injury and fluid accumulation characteristic of ARDS
IC14 is a chimeric monoclonal antibody that binds to CD14 with high affinity and inhibits signaling via membrane and soluble CD14 Blocking CD14 with IC14 treatment in normal volunteers strongly inhibits systemic inflammation in response to bacterial endotoxin LPS University of Washington conducted a small NIH-funded pilot trial of IC14 treatment in 13 patients with ARDS which suggested that IC14 treatment reduced alveolar inflammation and decreased BAL cytokines IC14 was also the subject of IND 105803 for a phase 2 study of ARDS from all causes which we propose to revise for the COVID-19 indication
A dosing regimen for IC14 with favorable pharmacokinetics supporting once daily intravenous dosing has been defined making this an acceptable treatment for hospitalized patients Two pharmacodynamic biomarkers can be used that are related to CD14 measurements of sCD14 serum at baseline urine at baseline and follow up as well as a CD14 fragment sCD14-ST presepsin A CD14 target engagement assay is available
Therefore because of the central role of CD14 in the amplification of lung inflammatory responses leading to severe lung injury and the safety record of IC14 in humans we propose to have an open-label protocol to test the safety and potential efficacy of IC14 treatment in preventing the progression of severe respiratory disease in patients hospitalized with COVID-19
IC14 is a chimeric monoclonal antibody that binds to CD14 with high affinity and inhibits signaling via membrane and soluble CD14 Blocking CD14 with IC14 treatment in normal volunteers strongly inhibits systemic inflammation in response to bacterial endotoxin LPS University of Washington conducted a small NIH-funded pilot trial of IC14 treatment in 13 patients with ARDS which suggested that IC14 treatment reduced alveolar inflammation and decreased BAL cytokines IC14 was also the subject of IND 105803 for a phase 2 study of ARDS from all causes which we propose to revise for the COVID-19 indication
A dosing regimen for IC14 with favorable pharmacokinetics supporting once daily intravenous dosing has been defined making this an acceptable treatment for hospitalized patients Two pharmacodynamic biomarkers can be used that are related to CD14 measurements of sCD14 serum at baseline urine at baseline and follow up as well as a CD14 fragment sCD14-ST presepsin A CD14 target engagement assay is available
Therefore because of the central role of CD14 in the amplification of lung inflammatory responses leading to severe lung injury and the safety record of IC14 in humans we propose to have an open-label protocol to test the safety and potential efficacy of IC14 treatment in preventing the progression of severe respiratory disease in patients hospitalized with COVID-19
Detailed Description:
This is a compassionate use open label program in patients hospitalized with pulmonary complications of SARS-CoV-2 infection who will receive IC14 at a dosage of 4 mgkg on Day 1 then 2 mgkg once daily on Days 2-4 Patient monitoring will be for a total of up to 28 days if the patient is still hospitalized
Screeningbaseline assessments and initiation of the first IC14 administration will occur within 48 hours after meeting inclusion criteria IC14 should be administered at approximately 24-hr intervals beginning from the start time of the first IC14 administration Day 1
Screeningbaseline assessments and initiation of the first IC14 administration will occur within 48 hours after meeting inclusion criteria IC14 should be administered at approximately 24-hr intervals beginning from the start time of the first IC14 administration Day 1
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None