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

COVID-19 Pneumonia Clinical Trial

— REMDACTA  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04409262
• Other study ID #: WA42511
• Secondary ID: 2020-002275-34
• Status: Completed
• Phase: Phase 3
• Start date: June 16, 2020
• Est. completion date: March 8, 2021

Study information

• Verified date: January 2022
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 649
• Est. completion date: March 8, 2021
• Est. primary completion date: February 1, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

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

Related Conditions & MeSH terms

• COVID-19
• COVID-19 Pneumonia
• Pneumonia

Intervention

Drug:
• Remdesivir
Participants will receive intravenous (IV) RDV
• Tocilizumab
Participants will receive IV TCZ
• Placebo
Participants will receive IV placebo matched to TCZ

Locations

Country	Name	City	State
Brazil	Santa Casa de Misericordia de Belo Horizonte	Belo Horizonte	MG
Brazil	Hospital Nossa Senhora das Graças; Setor de Pesquisa em Neurologia	Curitiba	PR
Brazil	Instituto de Pesquisa Clinica Evandro Chagas - IPEC FIOCRUZ	Rio de Janeiro	RJ
Brazil	CEMEC - Centro Multidisciplinar de Estudos Clínicos	Sao Bernardo Do Campo	SP
Brazil	Hospital de Base de Sao Jose do Rio Preto	Sao Jose do Rio Preto	SP
Brazil	Instituto de Infectologia Emilio Ribas	Sao Paulo	SP
Brazil	Instituto do Coração - HCFMUSP	Sao Paulo	SP
Russian Federation	City Clinical Hospital # 52	Moscow
Russian Federation	Medsi Clinic	Moscow	Adygeja
Russian Federation	O.M. Filatov City Clinical Hospital #15; Department of Surgery	Moskva	Moskovskaja Oblast
Russian Federation	City Pokrovskaya Hospital	Sankt-peterburg	Sankt Petersburg
Spain	Hospital Universitario Principe de Asturias; Medicina Interna - Servicio de Enfermedades Infecciosas	Alcala de Henares	Madrid
Spain	Hospital General Universitario de Guadalajara	Guadalajara
Spain	Hospital Universitario de Bellvitge	Hospitalet de Llobregat	Barcelona
Spain	Hospital Universitario Fundacion Jimenez Diaz.	Madrid
Spain	Hospital Universitario HM Torrelodones	Torrelodones	Madrid
United States	Lehigh Valley Hospital	Allentown	Pennsylvania
United States	The Liver Institute at Methodist Dallas	Arlington	Texas
United States	University of Maryland	Baltimore	Maryland
United States	St Luke's Health System; Rheumatology Research	Boise	Idaho
United States	Boston Medical Center	Boston	Massachusetts
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Novant Health Clinical Research	Charlotte	North Carolina
United States	eStudySite - Chula Vista - PPDS	Chula Vista	California
United States	Baylor Scott and White Medical Center - College Station	College Station	Texas
United States	OhioHealth Research Institute	Columbus	Ohio
United States	Baylor University Medical Center	Dallas	Texas
United States	The Providence Regional Medical Center Everett	Everett	Washington
United States	San Juan Oncology Associates	Farmington	New Mexico
United States	Holy Cross Hospital Inc	Fort Lauderdale	Florida
United States	Larkin Community Hospital Palm Springs Campus (Hialeah)	Hialeah	Florida
United States	Baylor St. Luke's Medical Center	Houston	Texas
United States	Ben Taub General Hospital - HCHD	Houston	Texas
United States	Houston Methodist Hospital	Houston	Texas
United States	Hoag Hospital Irvine	Irvine	California
United States	Baylor Scott & White Medical Center - Irving	Irving	Texas
United States	University of Miami Miller School of Medicine; Clinical Reseach Building	Miami	Florida
United States	West Virginia University Hospital	Morgantown	West Virginia
United States	Yale University School of Medicine; HIV Clinical Trials Program	New Haven	Connecticut
United States	Ochsner Clinic Foundation	New Orleans	Louisiana
United States	St. Michael'S Medical Center	Newark	New Jersey
United States	Henry Ford Medical Center	Novi	Michigan
United States	Advocate Christ Medical Center	Oak Lawn	Illinois
United States	Thomas Jefferson University	Philadelphia	Pennsylvania
United States	Valleywise Health Medical Center	Phoenix	Arizona
United States	Baylor Scott & White Hospital - Plano	Plano	Texas
United States	Providence Saint Vincent's Medical Center	Portland	Oregon
United States	Intermountain LDS Hospital	Salt Lake City	Utah
United States	Providence St Johns Health Center	Santa Monica	California
United States	Larkin Community Hospital	South Miami	Florida
United States	Baystate Medical Center	Springfield	Massachusetts
United States	Wyckoff Heights Medical Center	Staten Island	New York
United States	Baylor Scott & White Health	Temple	Texas
United States	Medstar Georgetown University Hospital	Washington	District of Columbia

Sponsors (2)

Lead Sponsor	Collaborator
Hoffmann-La Roche	Gilead Sciences

Countries where clinical trial is conducted

United States,  Brazil,  Russian Federation,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	Proportion of Participants With Any Post-Treatment Infection		Up to Day 60
Primary	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 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	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
Secondary	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 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
Secondary	Time to Death up to Day 28	Time to death is defined as the time from randomization to death.	Up to Day 28
Secondary	Time to Death up to Day 60	Time to death is defined as the time from randomization to death.	Up to Day 60
Secondary	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 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	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 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
Secondary	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 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
Secondary	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 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
Secondary	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 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
Secondary	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
Secondary	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
Secondary	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
Secondary	Difference in Mortality at Days 14, 28, and 60		Days 14, 28, and 60
Secondary	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 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	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 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	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