Sirolimus in COVID-19 Phase 1

Study Overview
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Brief Summary
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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.

Official Title
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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)

Conditions
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SARS-CoV-2, Covid-19

Intervention / Treatment
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* Drug: Sirolimus 1 MG/ML
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Sirolimus<br>Sirolimus + standard medical care Day 1: 10mg Days 2-7: 5mg | Drug: Sirolimus 1 MG/ML<br>* Oral solution<br>* Other names: Rapamune;|
| Placebo Comparator: Placebo<br>Placebo + standard medical care Day 1: 10mL Days 2-7: 5mL | Drug: Placebo<br>* Oral solution<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in SARS-CoV-2 viral burden from baseline to day 7 of treatment | SARS-CoV-2 viral burden will be quantified for both arms using a qRT-PCR | Baseline, and days 1, 2, 3, 4, 5, 6, & 7 post-dose for all patients | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in SARS-CoV-2 viral burden at days 1-6 | SARS-CoV-2 viral burden will be quantified for both arms using a qRT-PCR | Days 1, 2, 3, 4, 5, and 6 post-dose for all patients | 
| Rate of treatment emergent adverse events | Safety and tolerability of sirolimus in patients with COVID-19 | Days 1, 2, 3, 4, 5, and 6 post-dose for all patients |