IRAK4 Inhibition in Treatment of COVID-19 With ARDS (I-RAMIC)

COVID-19 Clinical Trial

Official title: Investigation of IRAK4 Inhibition to Mitigate the Impact of COVID-19 in Severe SARS-CoV-2 (I-RAMIC)

Status Terminated

Clinical Trial Summary

The purpose of this study is to assess the efficacy of PF-06650833 in addition to standard-of-care compared to standard-of-care treatment alone in improving outcomes in patients with COVID-19.

Clinical Trial Description

Proposed is a randomized, double-blind, placebo-controlled, parallel group Phase 2 study of the efficacy and safety of PF-06650833, an investigational drug, in hospitalized adult male and female patients with SARS-CoV-2-induced ARDS who need mechanical ventilation.

The primary objective of this study is to assess the efficacy of PF-06650833 in addition to standard-of-care compared to standard-of-care treatment alone in improving outcomes in patients with COVID-19, evidence of increased inflammation, and ARDS requiring mechanical ventilation or extracorporeal membrane oxygenation at time of admission.

The secondary objectives of this study are to evaluate:

1. Proportion of patients alive, extubated, and receiving no more that low flow oxygen supplementation by nasal cannula or face mask (excluding extubation for compassionate purposes in terminal patients). This would correspond to an at least 2-point improvement in the National Institute of Allergy and Infectious Diseases (NIAID) ordinal scale (1 = non hospitalized, no limitations on activity, and 8 = death) at Days 29 and 61

2. Proportion of patients alive, extubated, and receiving any level oxygen supplementation, including non-invasive positive pressure ventilation or high flow oxygen device (excluding extubation for compassionate purposes in terminal patients). This would correspond to an at least 1-point improvement in the NIAID ordinal scale (1 = non hospitalized, no limitations on activity, and 8 = death) at Days 29 and 61

3. Percentage of patients in each category of the NIAID 8-point ordinal scale of disease severity (Days 8, 15, 22, 29, and 61). The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows:

• Not hospitalized, no limitations on activities;

• Not hospitalized, limitation on activities and/or requiring home oxygen*

• Hospitalized, not requiring supplemental oxygen* - no longer requires ongoing medical care

• Hospitalized, not requiring supplemental oxygen* - requiring ongoing medical care (COVID-19 related or otherwise)

• Hospitalized, requiring supplemental oxygen*;

• Hospitalized, on non-invasive ventilation (NIV)** or high flow oxygen device;

• Hospitalized, on invasive mechanical ventilation or ECMO;

• Death

• For patients on chronic home O2 supplementation, supplemental O2 is defined as >= home O2 requirement.

• Use of NIV for chronic conditions [e.g. Obstructive sleep apnea (OSA)] is not applicable

4. Mortality rate at Day 61

5. Time to a 1-point improvement in the NIAID 8-point ordinal scale of disease severity

6. Time to a 2-point improvement in the NIAID 8-point ordinal scale of disease severity

7. Change from baseline in the ordinal scale from Day 1 to Days 3, 5, 8, 11, 15, 22, and

8. Arterial partial pressure of oxygen (PaO2) / Fractional concentration of inspired oxygen (FiO2) ratio (or P/F ratio)

9. Change of the Sequential Organ Failure Assessment (SOFA). The SOFA evaluates 6 variables, each representing an organ system (one for the respiratory, cardiovascular, hepatic, coagulation, renal and neurological systems), and scored from 0 (normal) to 4 (high degree of dysfunction/failure). Thus, the maximum score may range from 0 to 24.

10. Duration (days) of mechanical ventilation

11. Ventilator free days

12. Safety as assessed by reporting of adverse events (AEs), changes in clinical laboratory parameters (e.g., haemoglobin (Hb), white blood cell (WBC) count, platelets, hepatic transaminases, bilirubin, serum creatinine) ;

Related Conditions & MeSH terms

• COVID-19

• NCT number: NCT04575610
• Study type: Interventional
• Source: Yale University
• Status: Terminated
• Phase: Phase 2
• Start date: November 27, 2020
• Completion date: October 6, 2021