IRAK4 Inhibition in Treatment of COVID-19 With ARDS (I-RAMIC)
- Registration Number
- NCT04575610
- Lead Sponsor
- Yale University
- Brief 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.
- Detailed 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)
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 7
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description PF-06650833 + Standard of Care PF-06650833 Subjects randomized to the PF-06650833 arm of the study will receive 200 mg IR suspension formulation every 6 hours (via nasogastric \[NG\] tube, orogastric \[OG\] tube, or equivalent) if unable to take tablets by mouth (PO). All dosing of PF-06650833 will be in addition to current hospital SOC therapy. Placebo + Standard of Care Placebo Matching placebo tablets will be administered.
- Primary Outcome Measures
Name Time Method All-cause mortality at Day 29 Up to 29 days All-cause mortality at Day 29 (end of planned treatment period).
- Secondary Outcome Measures
Name Time Method Disease Severity (8 point scale) 29 days Change from baseline in the ordinal scale from Day 1 to Days 29.
Mortality 61 days Mortality rate at day 61
P/F ratio Up to 29 days PaO2 (partial pressure of oxygen) / FiO2 (fraction of inspired oxygen, FiO2) ratio (or P/F ratio)
Change of the SOFA score. Up to 29 days 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.
Duration (days) of mechanical ventilation Up to 29 days The duration is days spent on mechanical ventilation.
Ventilator free days. Up to 29 days The number of days hospitalized not on a ventilator.
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 Up to 29 days
Trial Locations
- Locations (1)
Yale New Haven Hospital
🇺🇸New Haven, Connecticut, United States