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 (REMDACTA)

A Phase III, Randomized, Double-Blind, Multicenter Study to Evaluate the Efficacy and Safety of Remdesivir Plus Tocilizumab Compared With Remdesivir Plus Placebo in Hospitalized Patients With Severe COVID-19 Pneumonia

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 Overview

• Status: Completed
• Conditions: COVID-19 Pneumonia
• Intervention / Treatment: Drug: Remdesivir; Drug: Tocilizumab; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 649
• Phase: Phase 3

Contacts and Locations

Study Locations

• Brazil
  • MG
    • Belo Horizonte, MG, Brazil, 30150-221
      • Santa Casa de Misericordia de Belo Horizonte
  • PR
    • Curitiba, PR, Brazil, 80810-040
      • Hospital Nossa Senhora das Graças; Setor de Pesquisa em Neurologia
  • RJ
    • Rio de Janeiro, RJ, Brazil, 21045-900
      • Instituto de Pesquisa Clinica Evandro Chagas - IPEC FIOCRUZ
  • SP
    • Sao Bernardo Do Campo, SP, Brazil, 09715-090
      • CEMEC - Centro Multidisciplinar de Estudos Clínicos
    • Sao Jose do Rio Preto, SP, Brazil, 15090-000
      • Hospital de Base de São José do Rio Preto
    • Sao Paulo, SP, Brazil, 05403-900
      • Instituto do Coração - HCFMUSP
    • Sao Paulo, SP, Brazil, 01246-000
      • Instituto de Infectologia Emilio Ribas
• Russian Federation
  • Moscow, Russian Federation, 123182
    • City Clinical Hospital # 52
  • Adygeja
    • Moscow, Adygeja, Russian Federation, 143442
      • Medsi Clinic
  • Moskovskaja Oblast
    • Moskva, Moskovskaja Oblast, Russian Federation, 111539
      • O.M. Filatov City Clinical Hospital #15; Department of Surgery
  • Sankt Petersburg
    • Sankt-peterburg, Sankt Petersburg, Russian Federation, 199106
      • City Pokrovskaya Hospital
• Spain
  • Guadalajara, Spain, 19002
    • Hospital General Universitario de Guadalajara
  • Madrid, Spain, 28040
    • Hospital Universitario Fundacion Jimenez Diaz.
  • Barcelona
    • Hospitalet de Llobregat, Barcelona, Spain, 08907
      • Hospital Universitario de Bellvitge
  • Madrid
    • Alcala de Henares, Madrid, Spain, 28005
      • Hospital Universitario Principe de Asturias; Medicina Interna - Servicio de Enfermedades Infecciosas
    • Torrelodones, Madrid, Spain, 28250
      • Hospital Universitario HM Torrelodones
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85008
      • Valleywise Health Medical Center
  • California
    • Chula Vista, California, United States, 91911
      • eStudySite - Chula Vista - PPDS
    • Irvine, California, United States, 92612
      • Hoag Hospital Irvine
    • Santa Monica, California, United States, 90404
      • Providence St Johns Health Center
  • Connecticut
    • New Haven, Connecticut, United States, 06501
      • Yale University School of Medicine; HIV Clinical Trials Program
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • MedStar Georgetown University Hospital
  • Florida
    • Fort Lauderdale, Florida, United States, 33308
      • Holy Cross Hospital Inc
    • Hialeah, Florida, United States, 33012
      • Larkin Community Hospital Palm Springs Campus (Hialeah)
    • Miami, Florida, United States, 33136
      • University of Miami Miller School of Medicine; Clinical Reseach Building
    • South Miami, Florida, United States, 33143
      • Larkin Community Hospital
  • Idaho
    • Boise, Idaho, United States, 83702
      • St Luke's Health System; Rheumatology Research
  • Illinois
    • Oak Lawn, Illinois, United States, 60453
      • Advocate Christ Medical Center
  • Louisiana
    • New Orleans, Louisiana, United States, 70121
      • Ochsner Clinic Foundation
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland
  • Massachusetts
    • Boston, Massachusetts, United States, 02118-2393
      • Boston Medical Center
    • Springfield, Massachusetts, United States, 01199
      • Baystate Medical Center
  • Michigan
    • Novi, Michigan, United States, 48322
      • Henry Ford Medical Center
  • New Jersey
    • Newark, New Jersey, United States, 07102
      • St. Michael's Medical Center
  • New Mexico
    • Farmington, New Mexico, United States, 87401
      • San Juan Oncology Associates
  • New York
    • Staten Island, New York, United States, 11237
      • Wyckoff Heights Medical Center
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Novant Health Clinical Research
  • Ohio
    • Columbus, Ohio, United States, 43214
      • OhioHealth Research Institute
  • Oregon
    • Portland, Oregon, United States, 97225
      • Providence Saint Vincent's Medical Center
  • Pennsylvania
    • Allentown, Pennsylvania, United States, 18103
      • LeHigh Valley Hospital
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
  • Texas
    • Arlington, Texas, United States, 76012
      • The Liver Institute at Methodist Dallas
    • College Station, Texas, United States, 77845
      • Baylor Scott and White Medical Center - College Station
    • Dallas, Texas, United States, 75231
      • Baylor University Medical Center
    • Houston, Texas, United States, 77030
      • Houston Methodist Hospital
    • Houston, Texas, United States, 77030
      • Baylor St. Luke's Medical Center
    • Houston, Texas, United States, 77030
      • Ben Taub General Hospital - HCHD
    • Irving, Texas, United States, 75061
      • Baylor Scott & White Medical Center - Irving
    • Plano, Texas, United States, 75093
      • Baylor Scott & White Hospital - Plano
    • Temple, Texas, United States, 76502
      • Baylor Scott & White Health
  • Utah
    • Salt Lake City, Utah, United States, 84143
      • Intermountain LDS Hospital
  • Washington
    • Everett, Washington, United States, 98201
      • The Providence Regional Medical Center Everett
  • West Virginia
    • Morgantown, West Virginia, United States, 26506
      • West Virginia University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Remdesivir + Tocilizumab (RDV+TCZ); Participants assigned to the RDV+TCZ arm will receive a 10-day treatment course of RDV, plus one infusion of TCZ on Day 1.	Drug: Remdesivir; Participants will receive intravenous (IV) RDV; Drug: Tocilizumab; Participants will receive IV TCZ
Active Comparator: Remdesivir + Placebo (RDV+Placebo); Participants assigned to the RDV+ placebo arm will receive a 10-day treatment course of RDV, plus one infusion of TCZ-placebo on Day 1.	Drug: Remdesivir; Participants will receive intravenous (IV) RDV; Drug: Placebo; Participants will receive IV placebo matched to TCZ

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.; Discharged (or "ready for discharge" as evidenced by normal temperature and respiratory rate, and stable oxygen saturation on ambient air or </= 2L supplemental oxygen); Non-intensive care unit (ICU) hospital ward (or "ready for hospital ward") not requiring supplemental oxygen; Non-ICU hospital ward (or "ready for hospital ward") requiring supplemental oxygen; ICU or non-ICU hospital ward, requiring non-invasive ventilation or high-flow oxygen; ICU, requiring intubation and mechanical ventilation; ICU, requiring extracorporeal membrane oxygenation (ECMO) or mechanical ventilation and additional organ support (e.g., vasopressors, renal replacement therapy); Death	Up to Day 28

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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: Discharged (or "ready for discharge" as evidenced by normal temperature and respiratory rate, and stable oxygen saturation on ambient air or </= 2L supplemental oxygen); Non-intensive care unit (ICU) hospital ward (or "ready for hospital ward") not requiring supplemental oxygen; Non-ICU hospital ward (or "ready for hospital ward") requiring supplemental oxygen; ICU or non-ICU hospital ward, requiring non-invasive ventilation or high-flow oxygen; ICU, requiring intubation and mechanical ventilation; ICU, requiring extracorporeal membrane oxygenation (ECMO) or mechanical ventilation and additional organ support (e.g., vasopressors, renal replacement therapy); Death	Day 14
Time to Death up to Day 28	Time to death is defined as the time from randomization to death.	Up to Day 28
Time to Death up to Day 60	Time to death is defined as the time from randomization to death.	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: Discharged (or "ready for discharge" as evidenced by normal temperature and respiratory rate, and stable oxygen saturation on ambient air or </= 2L supplemental oxygen); Non-intensive care unit (ICU) hospital ward (or "ready for hospital ward") not requiring supplemental oxygen; Non-ICU hospital ward (or "ready for hospital ward") requiring supplemental oxygen; ICU or non-ICU hospital ward, requiring non-invasive ventilation or high-flow oxygen; ICU, requiring intubation and mechanical ventilation; ICU, requiring extracorporeal membrane oxygenation (ECMO) or mechanical ventilation and additional organ support (e.g., vasopressors, renal replacement therapy); Death	Up to Day 28
Clinical Status as Assessed by the Investigator Using a 7-category Ordinal Scale of Clinical Status on Day 7	Clinical status was assessed by the investigator according to the following ordinal scale categories: Discharged (or "ready for discharge" as evidenced by normal temperature and respiratory rate, and stable oxygen saturation on ambient air or </= 2L supplemental oxygen); Non-intensive care unit (ICU) hospital ward (or "ready for hospital ward") not requiring supplemental oxygen; Non-ICU hospital ward (or "ready for hospital ward") requiring supplemental oxygen; ICU or non-ICU hospital ward, requiring non-invasive ventilation or high-flow oxygen; ICU, requiring intubation and mechanical ventilation; ICU, requiring extracorporeal membrane oxygenation (ECMO) or mechanical ventilation and additional organ support (e.g., vasopressors, renal replacement therapy); Death	Day 7
Clinical Status as Assessed by the Investigator Using a 7-category Ordinal Scale of Clinical Status on Day 21	Clinical status was assessed by the investigator according to the following ordinal scale categories: Discharged (or "ready for discharge" as evidenced by normal temperature and respiratory rate, and stable oxygen saturation on ambient air or </= 2L supplemental oxygen); Non-intensive care unit (ICU) hospital ward (or "ready for hospital ward") not requiring supplemental oxygen; Non-ICU hospital ward (or "ready for hospital ward") requiring supplemental oxygen; ICU or non-ICU hospital ward, requiring non-invasive ventilation or high-flow oxygen; ICU, requiring intubation and mechanical ventilation; ICU, requiring extracorporeal membrane oxygenation (ECMO) or mechanical ventilation and additional organ support (e.g., vasopressors, renal replacement therapy); Death	Day 21
Clinical Status as Assessed by the Investigator Using a 7-category Ordinal Scale of Clinical Status on Day 28	Clinical status was assessed by the investigator according to the following ordinal scale categories: Discharged (or "ready for discharge" as evidenced by normal temperature and respiratory rate, and stable oxygen saturation on ambient air or </= 2L supplemental oxygen); Non-intensive care unit (ICU) hospital ward (or "ready for hospital ward") not requiring supplemental oxygen; Non-ICU hospital ward (or "ready for hospital ward") requiring supplemental oxygen; ICU or non-ICU hospital ward, requiring non-invasive ventilation or high-flow oxygen; ICU, requiring intubation and mechanical ventilation; ICU, requiring extracorporeal membrane oxygenation (ECMO) or mechanical ventilation and additional organ support (e.g., vasopressors, renal replacement therapy); Death	Day 28
Clinical Status as Assessed by the Investigator Using a 7-category Ordinal Scale of Clinical Status on Day 60	Clinical status was assessed by the investigator according to the following ordinal scale categories: Discharged (or "ready for discharge" as evidenced by normal temperature and respiratory rate, and stable oxygen saturation on ambient air or </= 2L supplemental oxygen); Non-intensive care unit (ICU) hospital ward (or "ready for hospital ward") not requiring supplemental oxygen; Non-ICU hospital ward (or "ready for hospital ward") requiring supplemental oxygen; ICU or non-ICU hospital ward, requiring non-invasive ventilation or high-flow oxygen; ICU, requiring intubation and mechanical ventilation; ICU, requiring extracorporeal membrane oxygenation (ECMO) or mechanical ventilation and additional organ support (e.g., vasopressors, renal replacement therapy); Death	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.	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)		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.	Up to Day 28
Difference in Mortality at Days 14, 28, and 60		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.; Discharged (or "ready for discharge" as evidenced by normal temperature and respiratory rate, and stable oxygen saturation on ambient air or </= 2L supplemental oxygen); Non-intensive care unit (ICU) hospital ward (or "ready for hospital ward") not requiring supplemental oxygen; Non-ICU hospital ward (or "ready for hospital ward") requiring supplemental oxygen; ICU or non-ICU hospital ward, requiring non-invasive ventilation or high-flow oxygen; ICU, requiring intubation and mechanical ventilation; ICU, requiring extracorporeal membrane oxygenation (ECMO) or mechanical ventilation and additional organ support (e.g., vasopressors, renal replacement therapy); Death	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.; Discharged (or "ready for discharge" as evidenced by normal temperature and respiratory rate, and stable oxygen saturation on ambient air or </= 2L supplemental oxygen); Non-intensive care unit (ICU) hospital ward (or "ready for hospital ward") not requiring supplemental oxygen; Non-ICU hospital ward (or "ready for hospital ward") requiring supplemental oxygen; ICU or non-ICU hospital ward, requiring non-invasive ventilation or high-flow oxygen; ICU, requiring intubation and mechanical ventilation; ICU, requiring extracorporeal membrane oxygenation (ECMO) or mechanical ventilation and additional organ support (e.g., vasopressors, renal replacement therapy); Death	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.	Up to Day 28

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Adverse Events (AEs) Tabulated by Severity	AEs were reported according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE). Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated Grade 2: Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living (ADL) Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL Grade 4: Life-threatening consequences; urgent intervention indicated Grade 5: Death related to AE Participants are counted at the highest AE grade experienced.	Up to Day 60
Proportion of Participants With Any Post-Treatment Infection		Up to Day 60

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche
• Collaborators: Gilead Sciences

Study record dates

Study Major Dates

• Study Start (Actual): June 16, 2020
• Primary Completion (Actual): February 1, 2021
• Study Completion (Actual): March 8, 2021

Study Registration Dates

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

Study Record Updates

• Last Update Posted (Actual): February 14, 2022
• Last Update Submitted That Met QC Criteria: January 28, 2022
• Last Verified: January 1, 2022

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; Lung Diseases; COVID-19; Pneumonia; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Antimetabolites; Remdesivir
• Other Study ID Numbers: WA42511; 2020-002275-34 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No