Sirolimus Treatment in Hospitalized Patients With COVID-19 Pneumonia

Study Overview
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Brief Summary
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The main objective of our study is to determine if treatment with sirolimus can improve clinical outcomes in hospitalized patients with COVID-19. The investigators will employ a randomized, double blind, placebo-controlled study design. 30 subjects will be randomized in a 2:1 fashion to receive sirolimus or placebo. Sirolimus will be given as a 6mg oral loading dose on day 1 followed by 2mg daily for a maximum treatment duration of 14 days or until hospital discharge, whichever happens sooner. Chart reviews will be conducted daily to determine changes in clinical status, concomitant medications and laboratory parameters. Study specific biomarkers will be measured at baseline and then at days 3, 7 and 14.

Official Title
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Sirolimus Treatment in Hospitalized Patients With COVID-19 Pneumonia (The SCOPE Trial)

Conditions
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COVID-19

Intervention / Treatment
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* Drug: Sirolimus
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects enrolled in the trial must meet all of the following criteria. Confirmed COVID-19 pneumonia Hypoxia as defined by room air oxygen saturation less than 92% or supplemental oxygen requirement Presence of at least one additional biomarker that has been shown to predict poor prognosis: a) serum ferritin ≥500ug/l, b) LDH ≥250U/L, c) d-dimer ≥1ug/L, or d) lymphopenia as defined by absolute lymphocyte count <1,000/uL Age ≥ 18 years Completed informed consent Exclusion Criteria: Subjects who meet ANY of the following criteria are not eligible for enrollment as study participants: Known allergy or hypersensitivity to sirolimus Inability or refusal to provide informed consent Advanced respiratory support (high flow oxygen ≥ 15 L/min, CPAP, non-invasive or invasive mechanical ventilation) Active enrollment in other interventional clinical drug trials. Co-enrollment in observational studies and biorepositories is allowed. Pregnant women Breast feeding On chronic immunosuppression for other medical conditions such as rheumatological disorders, inflammatory bowel disease, or in patients with organ transplants. A list of these medications is provided in Section 12.3.4 Any clinically significant medical disease which in the opinion of the investigator precludes the patient from enrolling in the trial, including (but not limited to): History of liver cirrhosis End stage renal disease or need for renal replacement therapy Decompensated heart failure Known active tuberculosis or history of incompletely treated tuberculosis Uncontrolled systemic bacterial or fungal infections Active viral infection other than COVID-19

Ages Eligible for Study
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Minimum Age: 18 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
Interventional Model Description: Randmized, double blind, placebo controlled
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Sirolimus<br>Sirolimus 6mg on day 1 followed by 2mg daily for the next 13 days or until hospital discharge, whatever happens sooner. | Drug: Sirolimus<br>* Sirolimus 6mg daily on Day 1 followed by 2mg daily for the next 13 days for a total treatment duration of 14 days or hospital discharge, whatever happens sooner.<br>* Other names: Rapamycin;|
| Placebo Comparator: Placebo<br>Matching placebo | Drug: Placebo<br>* Matching placebo<br>* Other names: placebo capsules;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients who are alive and free from advanced respiratory support measures at day 28. | Death or progression to respiratory failure requiring advanced support measures, either due to inadequate ventilation (non-invasive or invasive mechanical ventilation) or inadequate oxygenation (CPAP* or high flow supplemental oxygen at rates ≥ 15 liters/minute), in patients given sirolimus compared to the placebo group. * CPAP use for known obstructive sleep apnea will not be considered as disease progression. | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients who require escalation in care | Progression to a higher level of care, e.g. ICU | 14 days | 
| Change over time in study-specific biomarkers (LDH, Ferritin, D-dimer, lymphocyte count) | Change over time in study-specific biomarkers (LDH, Ferritin, D-dimer, lymphocyte count) | 14 days | 
| Proportion of patients surviving to hospital discharge | Survival to hospital discharge | days | 
| Drug safety profile | Incidence and type of adverse events | 14 days | 
| Duration of advanced respiratory support | Number of days spent on advanced respiratory support measures | days | 
| Duration of hospital stay | Length of hospitalization (in patients who survive to discharge) | days | 
| Time from treatment initiation to death | Number of days between study initiation and death (in the subset of patients who die during the hospitalization) | days | 
| Time to resolution of fever | Time (in days) to resolution of fever | 14 days | 
| Proportion of patients who require initiation of off-label therapies | Patients needing off-label treatments such as Anti-IL-6 inhibitors at the discretion of primary clinicians | 14 days |