IRAK4 Inhibition in Treatment of COVID-19 With ARDS (I-RAMIC)
COVID-19
About this trial
This is an interventional treatment trial for COVID-19 focused on measuring Protein Kinase Inhibitors, Enzyme Inhibitors, Molecular Mechanisms of Pharmacological Action
Eligibility Criteria
INCLUSION CRITERIA
- Adult male and female patients, including women of childbearing potential, at least 18 years of age, inclusive
- Participant (or legally authorized representative) capable of giving signed informed consent
- Laboratory-confirmed novel coronavirus (SARS-CoV-2) infection
- Clinical findings and an imaging study consistent with ARDS;
- PaO2 / FiO2 ratio < 300;
- A requirement for mechanical ventilation ≤ 48 hours prior to enrollment.
Evidence of increased inflammation as assessed by hsCRP > ULN AND at least ONE of the following being > upper limit of normal (as available):
- ferritin
- procalcitonin
- D-dimer
- fibrinogen
- LDH
- PT/PTT
EXCLUSION CRITERIA
- Suspected or known active systemic bacterial, viral (except SARS-CoV2 infection), or fungal infections
- Active herpes zoster infection
- Known active or latent tuberculosis (TB) or history of inadequately treated TB
- Active hepatitis B or hepatitis C
- Known history of human immunodeficiency virus (HIV) infection with a detectable viral load or CD4 count < 500 cells / mm3 (patients for whom documented viral load or CD4 counts are available will be excluded)
- Active hematologic cancer
- Metastatic or intractable cancer
- Pre-existing neurodegenerative disease
- Severe hepatic impairment defined as Child-Pugh Class B or Class C at baseline
- Severe renal impairment with an estimated glomerular filtration rate (eGFR) < 45 mL/min/1.73 m2
- Severe anemia (Hb < 8.0 g/dL)
Any of the following abnormal laboratory values:
- absolute lymphocyte count <250 cells/mm3
- absolute neutrophil Count (ANC) <1000 cells/mm3
- Platelet count <50,000 cells/mm3
- ALT or AST > 5X ULN, or other evidence of hepatocellular synthetic dysfunction or total bilirubin > 2X ULN
- Any other medical condition or laboratory abnormality that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study
- Prohibited concomitant therapy (see section 1.12.7.2)
- Pregnancy (a negative urine or serum pregnancy test is required for inclusion)
- Immunocompromised patients, patients with known immunodeficiencies or taking potent immunosuppressive agents (e.g., azathioprine, cyclosporine)
- Anticipated survival < 72 hours as assessed by the Investigator.
- Participation in other clinical trials of investigational treatments for COVID-19
- Known history of nephrolithiasis
Sites / Locations
- Yale New Haven Hospital
Arms of the Study
Arm 1
Arm 2
Experimental
Active Comparator
PF-06650833 + Standard of Care
Placebo + Standard of Care
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.
Matching placebo tablets will be administered.