Clinical trial NCT04409262: 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: COVID-19 Pneumonia
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
Collaborators: name: Gilead Sciences
First posted: 2020-06-01
Enrollment: 649
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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

Primary outcomes:
measure: Time to Hospital Discharge or "Ready for Discharge" up to Day 28
timeFrame: Up to Day 28
Secondary outcomes:
measure: Time to Mechanical Ventilation or Death up to Day 28
timeFrame: Up to Day 28
measure: Clinical Status as Assessed by the Investigator Using a 7-category Ordinal Scale of Clinical Status on Day 14
timeFrame: Day 14
measure: Time to Death up to Day 28
timeFrame: Up to Day 28
measure: Time to Death up to Day 60
timeFrame: Up to Day 60
measure: Time to Improvement of at Least 2 Categories Relative to Baseline on a 7-category Ordinal Scale of Clinical Status up to Day 28
timeFrame: Up to Day 28
measure: Clinical Status as Assessed by the Investigator Using a 7-category Ordinal Scale of Clinical Status on Day 7
timeFrame: Day 7
measure: Clinical Status as Assessed by the Investigator Using a 7-category Ordinal Scale of Clinical Status on Day 21
timeFrame: Day 21
measure: Clinical Status as Assessed by the Investigator Using a 7-category Ordinal Scale of Clinical Status on Day 28
timeFrame: Day 28
measure: Clinical Status as Assessed by the Investigator Using a 7-category Ordinal Scale of Clinical Status on Day 60
timeFrame: Day 60
measure: Proportion of Participants Requiring Initiation of Mechanical Ventilation Post-baseline (Participants Who Did Not Require Mechanical Ventilation at Baseline)
timeFrame: Day 28 and Day 60
measure: Proportion of Participants Who Are Alive and Free of Respiratory Failure at Day 28 and Day 60 (Participants Requiring Mechanical Ventilation at Baseline)
timeFrame: Day 28 and Day 60
measure: Duration of Mechanical Ventilation (Participants Requiring Mechanical Ventilation at Baseline) up to Day 28
timeFrame: Up to Day 28
measure: Difference in Mortality at Days 14, 28, and 60
timeFrame: Days 14, 28, and 60
measure: Time to Recovery up to Day 28
timeFrame: Up to Day 28
measure: Proportion of Participants Who Are Discharged or "Ready for Discharge" up to Day 28
timeFrame: Up to Day 28
measure: Proportion of Participants Who Require Initiation of Mechanical Ventilation Post-baseline or Die up to Day 28
timeFrame: Up to Day 28
Other outcomes:
measure: Percentage of Participants With Adverse Events (AEs) Tabulated by Severity
timeFrame: Up to Day 60
measure: Proportion of Participants With Any Post-Treatment Infection
timeFrame: Up to Day 60
Locations:
city: Phoenix
country: United States
facility: Valleywise Health Medical Center
state: Arizona
city: Chula Vista
country: United States
facility: eStudySite - Chula Vista - PPDS
state: California
city: Irvine
country: United States
facility: Hoag Hospital Irvine
state: California
city: Santa Monica
country: United States
facility: Providence St Johns Health Center
state: California
city: New Haven
country: United States
facility: Yale University School of Medicine; HIV Clinical Trials Program
state: Connecticut
city: Washington
country: United States
facility: Medstar Georgetown University Hospital
state: District of Columbia
city: Fort Lauderdale
country: United States
facility: Holy Cross Hospital Inc
state: Florida
city: Hialeah
country: United States
facility: Larkin Community Hospital Palm Springs Campus (Hialeah)
state: Florida
city: Miami
country: United States
facility: University of Miami Miller School of Medicine; Clinical Reseach Building
state: Florida
city: South Miami
country: United States
facility: Larkin Community Hospital
state: Florida
city: Boise
country: United States
facility: St Luke's Health System; Rheumatology Research
state: Idaho
city: Oak Lawn
country: United States
facility: Advocate Christ Medical Center
state: Illinois
city: New Orleans
country: United States
facility: Ochsner Clinic Foundation
state: Louisiana
city: Baltimore
country: United States
facility: University of Maryland
state: Maryland
city: Boston
country: United States
facility: Boston Medical Center
state: Massachusetts
city: Springfield
country: United States
facility: Baystate Medical Center
state: Massachusetts
city: Novi
country: United States
facility: Henry Ford Medical Center
state: Michigan
city: Newark
country: United States
facility: St. Michael'S Medical Center
state: New Jersey
city: Farmington
country: United States
facility: San Juan Oncology Associates
state: New Mexico
city: Staten Island
country: United States
facility: Wyckoff Heights Medical Center
state: New York
city: Charlotte
country: United States
facility: Novant Health Clinical Research
state: North Carolina
city: Columbus
country: United States
facility: OhioHealth Research Institute
state: Ohio
city: Portland
country: United States
facility: Providence Saint Vincent's Medical Center
state: Oregon
city: Allentown
country: United States
facility: Lehigh Valley Hospital
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Arlington
country: United States
facility: The Liver Institute at Methodist Dallas
state: Texas
city: College Station
country: United States
facility: Baylor Scott and White Medical Center - College Station
state: Texas
city: Dallas
country: United States
facility: Baylor University Medical Center
state: Texas
city: Houston
country: United States
facility: Baylor St. Luke's Medical Center
state: Texas
city: Houston
country: United States
facility: Ben Taub General Hospital - HCHD
state: Texas
city: Houston
country: United States
facility: Houston Methodist Hospital
state: Texas
city: Irving
country: United States
facility: Baylor Scott & White Medical Center - Irving
state: Texas
city: Plano
country: United States
facility: Baylor Scott & White Hospital - Plano
state: Texas
city: Temple
country: United States
facility: Baylor Scott & White Health
state: Texas
city: Salt Lake City
country: United States
facility: Intermountain LDS Hospital
state: Utah
city: Everett
country: United States
facility: The Providence Regional Medical Center Everett
state: Washington
city: Morgantown
country: United States
facility: West Virginia University Hospital
state: West Virginia
city: Belo Horizonte
country: Brazil
facility: Santa Casa de Misericordia de Belo Horizonte
state: MG
city: Curitiba
country: Brazil
facility: Hospital Nossa Senhora das Graças; Setor de Pesquisa em Neurologia
state: PR
city: Rio de Janeiro
country: Brazil
facility: Instituto de Pesquisa Clinica Evandro Chagas - IPEC FIOCRUZ
state: RJ
city: Sao Bernardo Do Campo
country: Brazil
facility: CEMEC - Centro Multidisciplinar de Estudos Clínicos
state: SP
city: Sao Jose do Rio Preto
country: Brazil
facility: Hospital de Base de Sao Jose do Rio Preto
state: SP
city: Sao Paulo
country: Brazil
facility: Instituto de Infectologia Emilio Ribas
state: SP
city: Sao Paulo
country: Brazil
facility: Instituto do Coração - HCFMUSP
state: SP
city: Moscow
country: Russian Federation
facility: Medsi Clinic
state: Adygeja
city: Moskva
country: Russian Federation
facility: O.M. Filatov City Clinical Hospital #15; Department of Surgery
state: Moskovskaja Oblast
city: Sankt-peterburg
country: Russian Federation
facility: City Pokrovskaya Hospital
state: Sankt Petersburg
city: Moscow
country: Russian Federation
facility: City Clinical Hospital # 52
city: Hospitalet de Llobregat
country: Spain
facility: Hospital Universitario de Bellvitge
state: Barcelona
city: Alcala de Henares
country: Spain
facility: Hospital Universitario Principe de Asturias; Medicina Interna - Servicio de Enfermedades Infecciosas
state: Madrid
city: Torrelodones
country: Spain
facility: Hospital Universitario HM Torrelodones
state: Madrid
city: Guadalajara
country: Spain
facility: Hospital General Universitario de Guadalajara
city: Madrid
country: Spain
facility: Hospital Universitario Fundacion Jimenez Diaz.
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: