IRAK 4 Inhibitor (PF-06650833) in Hospitalized Patients With COVID-19 Pneumonia and Exuberant Inflammation.

• Status: Recruiting
• Trial end date: 2022-05-06
• Target enrollment: 0
• Participant gender: All

Summary

The aim of the current clinical study is to evaluate the efficacy and safety of inhibition of Interleukin-1 receptor associated kinase 4 (IRAK4) in ameliorating the proinflammatory state and improving outcomes in severe COVID-19.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Giovanni Franchin, M.D, Ph.D
• Collaborator: Pfizer

Criteria

Inclusion Criteria:

1. Hospitalized adult male and female patients, including women of childbearing potential, at least 18 years of age, inclusive. Women of childbearing potential must agree to the protocol-specific contraception requirements.

2. Participant (or legally authorized representative) capable of giving signed informed consent.

3. Laboratory-confirmed novel coronavirus (SARS-CoV-2) infection.

4. Evidence of pneumonia assessed by ALL of the following:

1. Radiographic imaging (eg, chest x-ray, chest computed tomography [CT] scan, etc.); AND

2. Clinical assessment (evidence of rales/crackles on exam); AND

3. SpO2 ≤94% on room air.

5. Evidence of increased inflammation as assessed by hsCRP > ULN AND at least ONE of the following being > ULN (as available):

1. Ferritin;

2. Procalcitonin;

3. D-dimer;

4. Fibrinogen;

5. LDH;

6. PT/PTT.

Exclusion Criteria:

1. Other medical condition other than COVID-19 or laboratory abnormality that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study, eg, acute coronary syndrome.

2. Suspected or known active systemic bacterial, viral (except SARS-CoV2 infection) or fungal infections

3. Active herpes zoster infection.

4. Known active or latent tuberculosis (TB) or history of inadequately treated TB.

5. Active hepatitis B or hepatitis C.

• Patients with positive hepatitis B surface antigen (HBsAg) will be excluded. Patients who are HBsAg negative but hepatitis B core antibody (HBcAb) positive will need a negative hepatitis B virus deoxyribonucleic acid (HBV DNA) to be allowed to enroll in the study; if the HBV DNA is positive, they will be not eligible.

• Patients with a positive test for hepatitis C virus (hepatitis C virus antibody; HCV Ab) will need a negative hepatitis C virus ribonucleic acid (HCV RNA; or negative HCV Ab test) and normal liver function (as assessed by liver transaminases and bilirubin within protocol-permitted limits, and no other evidence of compromised liver synthetic ability (eg, albumin and coagulation tests within protocol-permitted limits) to be allowed to enroll in the study, provided other eligibility criteria are met.

6. Known history of human immunodeficiency virus (HIV) infection with a detectable viral load or CD4 count <500 cells/mm3 (or patients for whom documentation of viral load or CD4 counts are not available) will be excluded; patients on highly active anti retroviral treatment, undetectable HIV viral load, and CD4 counts ≥500 cells/mm3 would be eligible).

7. Active hematologic cancer.

8. Metastatic or intractable cancer.

9. Pre-existing neurodegenerative disease.

10. Proven bacterial pneumonia, other serious infection, sepsis, and/septic shock.

11. Requirement for mechanical ventilation, or extracorporeal membrane oxygenation.

12. Severe hepatic impairment defined as Child-Pugh Class B or Class C at baseline.

13. Severe renal impairment with an estimated glomerular filtration rate (eGFR) <50 mL/min/1.73 m2.

14. Known history of nephrolithiasis.

15. Severe anemia (Hb <8.0 g/dL).

16. Any of the following abnormal laboratory vales:

1. Absolute lymphocyte count <500 cells/mm3;

2. Absolute neutrophil count (ANC) <1500 cells/mm3;

3. Platelet count <50,000 cells/mm3;

4. ALT or AST >5X ULN, or total bilirubin >2X ULN, or other evidence of hepatocellular synthetic dysfunction.

17. 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.

18. Prohibited concomitant therapy.

19. Pregnancy (a negative urine or serum pregnancy test is required for inclusion) or breastfeeding.

20. Immunocompromised patients, patients with known immunodeficiencies or taking potent immunosuppressive agents (eg, azathioprine, cyclosporine).

21. Anticipated survival <72 hours as assessed by the Investigator.

22. Participation in other clinical trials of investigational treatments for COVID-19.