Sirolimus in COVID-19 Phase 1 (SirCO-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.

Study Overview

• Status: Withdrawn
• Conditions: Covid-19; SARS-CoV-2
• Intervention / Treatment: Drug: Placebo; Drug: Sirolimus 1 MG/ML

• Study Type: Interventional
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Walter K. Kraft
• Investigators: Principal Investigator: Walter K Kraft, MD, Thomas Jefferson University

Study record dates

Study Major Dates

• Study Start (Actual): July 6, 2020
• Primary Completion (Actual): July 30, 2021
• Study Completion (Actual): July 30, 2021

Study Registration Dates

• First Submitted: April 28, 2020
• First Submitted That Met QC Criteria: April 28, 2020
• First Posted (Actual): May 1, 2020

Study Record Updates

• Last Update Posted (Actual): December 3, 2021
• Last Update Submitted That Met QC Criteria: December 2, 2021
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Physiological Effects of Drugs; Anti-Infective Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antifungal Agents; Sirolimus
• Other Study ID Numbers: 15680

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes