Sirolimus in COVID-19 Phase 1

A Randomized, Double-Blinded, Placebo-Controlled Trial Evaluating the Virological Efficacy, Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Sirolimus Adjuvant Therapy in Patients With Coronavirus Disease (COVID-19)

This is a double-blinded, two-arm, randomized, placebo controlled study comparing the virological efficacy of add-on sirolimus with standard care to placebo and standard care. Virological efficacy is defined as the change from baseline to day 7 in SARS-CoV-2 viral burden measured by quantitative real-time polymerase chain reaction.

Inclusion Criteria:

• Male or non-pregnant female >/=18 and </=65 years of age at the time of consent
• Laboratory confirmed SARS-CoV-2 infection
• Investigator-estimated hospitalization duration of at least 5 days

Exclusion Criteria:

• Need for >4 liters nasal cannula oxygen to maintain oxygen saturation >90%
• Hypersensitivity to sirolimus
• Pregnant or breastfeeding
• Anticipated transfer to another study hospital within 72 hours
• Alanine transaminase (ALT) >3 times the upper limit of normal
• Creatinine clearance <30mL/min as estimated by Cockcroft-Gault
• Underlying immunosuppression due to daily >5 mg prednisone equivalent a day, prior solid organ transplant, or other immunosuppression deemed by investigator to be potentially unsafe
• Co-administration with strong inhibitors of CYP3A4 and/or P-glycoprotein (P-gp) (such as ketoconazole, voriconazole, itraconazole, telithromycin, clarithromycin and others)
• Co-administration with strong inducers of CYP3A4 and/or P-glycoprotein (P-gp) (such as phenytoin or rifampin)
• Anticipated surgery within 1 month
• Need for healing of a fracture or a significant soft tissue wound