A Study to Evaluate the Efficacy and Safety of Remdesivir Plus Tocilizumab Compared With Remdesivir Plus Placebo in Hospitalized Participants With Severe COVID-19 Pneumonia

Hoffmann-La Roche649 enrolled

Overview

This study will evaluate the efficacy and safety of combination therapy with remdesivir plus tocilizumab compared with remdesivir plus placebo in hospitalized patients with COVID-19 pneumonia.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

649

Conditions

COVID-19 Pneumonia

Interventions

RemdesivirDRUG

Participants will receive intravenous (IV) RDV

TocilizumabDRUG

Participants will receive IV TCZ

PlaceboDRUG

Participants will receive IV placebo matched to TCZ

Eligibility

Sex: ALLMin age: 12 Years

Medical Language ↔ Plain English

Inclusion Criteria * Hospitalized with COVID-19 pneumonia confirmed per a positive polymerase chain reaction (PCR) of any specimen (e.g., respiratory, blood, urine, stool, other bodily fluid) and evidenced by chest X-ray or CT scan * Requiring more than 6 L/min supplemental oxygen to maintain SpO2 \> 93% * Agrees to not participate in another clinical trial for the treatment of COVID-19 while participating in this study Exclusion Criteria * Known severe allergic reactions to tocilizumab or other monoclonal antibodies * Known hypersensitivity to remdesivir, the metabolites, or formulation excipients * Active tuberculosis (TB) infection * Suspected active bacterial, fungal, viral, or other infection (besides COVID-19) * In the opinion of the investigator, progression to death is imminent and inevitable within the next 24 hours, irrespective of the provision of treatments * Treatment with immunosuppressive or immunomodulatory therapy (including tocilizumab) within the past 3 months * Concurrent treatment with other agents with actual or possible direct-acting antiviral activity against SARS-CoV-2 within 24 hours prior to study drug dosing. In addition, participants with prior or current treatment with \> 2 doses of remdesivir for COVID-19 are excluded * Participating in other drug clinical trials * Estimated glomerular filtration rate (eGFR) \< 30 mL/min (including patients receiving hemodialysis or hemofiltration) * Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \> 5 x upper limit of normal (ULN) detected within 24 hours of screening (according to local laboratory reference ranges) * Absolute neutrophil count (ANC) \< 1000/uL at screening * Platelet count \< 50,000/uL at screening * Body weight \< 40 kg * Treatment with an investigational drug within 5 half-lives or 30 days (whichever is longer) of randomization

Locations (54)

Outcomes

Primary Outcomes

Time to Hospital Discharge or "Ready for Discharge" up to Day 28

Defined as days from randomization to hospital discharge or "Ready for Discharge" not followed by ordinal scale category \>1, hospital readmission or death. Hospital discharge or "Ready for Discharge" is defined as an ordinal score of 1 on the 7-point ordinal scale. Participants who die are censored at Day 28. 1. Discharged (or "ready for discharge" as evidenced by normal temperature and respiratory rate, and stable oxygen saturation on ambient air or \</= 2L supplemental oxygen) 2. Non-intensive care unit (ICU) hospital ward (or "ready for hospital ward") not requiring supplemental oxygen 3. Non-ICU hospital ward (or "ready for hospital ward") requiring supplemental oxygen 4. ICU or non-ICU hospital ward, requiring non-invasive ventilation or high-flow oxygen 5. ICU, requiring intubation and mechanical ventilation 6. ICU, requiring extracorporeal membrane oxygenation (ECMO) or mechanical ventilation and additional organ support (e.g., vasopressors, renal replacement therapy) 7. Death

Time frame: Up to Day 28

Secondary Outcomes

Time to Mechanical Ventilation or Death up to Day 28

Time to Mechanical Ventilation or Death defined as the time from randomization to the first occurrence of death or mechanical ventilation. For participants already on mechanical ventilation at baseline, only death is counted as an event.

Time frame: Up to Day 28

Clinical Status as Assessed by the Investigator Using a 7-category Ordinal Scale of Clinical Status on Day 14

Clinical status was assessed by the investigator according to the following ordinal scale categories: 1. Discharged (or "ready for discharge" as evidenced by normal temperature and respiratory rate, and stable oxygen saturation on ambient air or \</= 2L supplemental oxygen) 2. Non-intensive care unit (ICU) hospital ward (or "ready for hospital ward") not requiring supplemental oxygen 3. Non-ICU hospital ward (or "ready for hospital ward") requiring supplemental oxygen 4. ICU or non-ICU hospital ward, requiring non-invasive ventilation or high-flow oxygen 5. ICU, requiring intubation and mechanical ventilation 6. ICU, requiring extracorporeal membrane oxygenation (ECMO) or mechanical ventilation and additional organ support (e.g., vasopressors, renal replacement therapy) 7. Death

Data from ClinicalTrials.gov

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Valleywise Health Medical Center

Phoenix, Arizona, United States

eStudySite - Chula Vista - PPDS

Chula Vista, California, United States

Hoag Hospital Irvine

Irvine, California, United States

Providence St Johns Health Center

Santa Monica, California, United States

Yale University School of Medicine; HIV Clinical Trials Program

New Haven, Connecticut, United States

Medstar Georgetown University Hospital

Washington D.C., District of Columbia, United States

Holy Cross Hospital Inc

Fort Lauderdale, Florida, United States

Larkin Community Hospital Palm Springs Campus (Hialeah)

Hialeah, Florida, United States

University of Miami Miller School of Medicine; Clinical Reseach Building

Miami, Florida, United States

Larkin Community Hospital

South Miami, Florida, United States

...and 44 more locations

Time to Death up to Day 28

Time to death is defined as the time from randomization to death.

Time frame: Up to Day 28

Time to Death up to Day 60

Time to death is defined as the time from randomization to death.

Time frame: Up to Day 60

Time to Improvement of at Least 2 Categories Relative to Baseline on a 7-category Ordinal Scale of Clinical Status up to Day 28

Defined as time from randomization to the time when at least a 2-category improvement in the 7-category ordinal scale is observed. Patients who die are censored at day 28. Clinical status was assessed by the investigator according to the following ordinal scale categories: 1. Discharged (or "ready for discharge" as evidenced by normal temperature and respiratory rate, and stable oxygen saturation on ambient air or \</= 2L supplemental oxygen) 2. Non-intensive care unit (ICU) hospital ward (or "ready for hospital ward") not requiring supplemental oxygen 3. Non-ICU hospital ward (or "ready for hospital ward") requiring supplemental oxygen 4. ICU or non-ICU hospital ward, requiring non-invasive ventilation or high-flow oxygen 5. ICU, requiring intubation and mechanical ventilation 6. ICU, requiring extracorporeal membrane oxygenation (ECMO) or mechanical ventilation and additional organ support (e.g., vasopressors, renal replacement therapy) 7. Death

Time frame: Up to Day 28

Clinical Status as Assessed by the Investigator Using a 7-category Ordinal Scale of Clinical Status on Day 7

Time frame: Day 7

Clinical Status as Assessed by the Investigator Using a 7-category Ordinal Scale of Clinical Status on Day 21

Time frame: Day 21

Clinical Status as Assessed by the Investigator Using a 7-category Ordinal Scale of Clinical Status on Day 28

Time frame: Day 28

Clinical Status as Assessed by the Investigator Using a 7-category Ordinal Scale of Clinical Status on Day 60

Time frame: Day 60

Proportion of Participants Requiring Initiation of Mechanical Ventilation Post-baseline (Participants Who Did Not Require Mechanical Ventilation at Baseline)

Day 28: Participants who withdraw or die prior to Day 28 are assumed to have required mechanical ventilation. Participants without mechanical ventilation prior to discharge are assumed not to have required mechanical ventilation unless they die by Day 28, which are counted as an event. Day 60: Participants who withdraw or die prior to Day 60 are assumed to have required mechanical ventilation. Participants without mechanical ventilation prior to discharge are assumed not to have required mechanical ventilation unless they die by Day 60, which are counted as an event.

Time frame: Day 28 and Day 60

Proportion of Participants Who Are Alive and Free of Respiratory Failure at Day 28 and Day 60 (Participants Requiring Mechanical Ventilation at Baseline)

Time frame: Day 28 and Day 60

Duration of Mechanical Ventilation (Participants Requiring Mechanical Ventilation at Baseline) up to Day 28

Participants who die by Day 28 are assigned a duration of 28 days.

Time frame: Up to Day 28

Difference in Mortality at Days 14, 28, and 60

Time frame: Days 14, 28, and 60

Time to Recovery up to Day 28

Defined as the time from randomization to the time when an ordinal scale category of 2 (non-ICU hospital ward or "ready for hospital ward" not requiring supplemental oxygen) or better is observed, not followed by ordinal scale category \>2 or death. Participants who die are censored at day 28. 1. Discharged (or "ready for discharge" as evidenced by normal temperature and respiratory rate, and stable oxygen saturation on ambient air or \</= 2L supplemental oxygen) 2. Non-intensive care unit (ICU) hospital ward (or "ready for hospital ward") not requiring supplemental oxygen 3. Non-ICU hospital ward (or "ready for hospital ward") requiring supplemental oxygen 4. ICU or non-ICU hospital ward, requiring non-invasive ventilation or high-flow oxygen 5. ICU, requiring intubation and mechanical ventilation 6. ICU, requiring extracorporeal membrane oxygenation (ECMO) or mechanical ventilation and additional organ support (e.g., vasopressors, renal replacement therapy) 7. Death

Time frame: Up to Day 28

Proportion of Participants Who Are Discharged or "Ready for Discharge" up to Day 28

Defined as hospital discharge or "Ready for Discharge" not followed by ordinal scale category \>1, hospital readmission or death. 1. Discharged (or "ready for discharge" as evidenced by normal temperature and respiratory rate, and stable oxygen saturation on ambient air or \</= 2L supplemental oxygen) 2. Non-intensive care unit (ICU) hospital ward (or "ready for hospital ward") not requiring supplemental oxygen 3. Non-ICU hospital ward (or "ready for hospital ward") requiring supplemental oxygen 4. ICU or non-ICU hospital ward, requiring non-invasive ventilation or high-flow oxygen 5. ICU, requiring intubation and mechanical ventilation 6. ICU, requiring extracorporeal membrane oxygenation (ECMO) or mechanical ventilation and additional organ support (e.g., vasopressors, renal replacement therapy) 7. Death

Time frame: Up to Day 28

Proportion of Participants Who Require Initiation of Mechanical Ventilation Post-baseline or Die up to Day 28

Participants already on mechanical ventilation at baseline are only counted as an event if death occurs.

Time frame: Up to Day 28