Clinical trial NCT04320615: A Study to Evaluate the Safety and Efficacy of Tocilizumab in Patients With Severe COVID-19 Pneumonia
Official title: A Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Safety and Efficacy of Tocilizumab in 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
First posted: 2020-03-25
Enrollment: 452
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study will evaluate the efficacy, safety, pharmacodynamics, and pharmacokinetics of tocilizumab (TCZ) compared with a matching placebo in combination with standard of care (SOC) in hospitalized patients with severe COVID-19 pneumonia.


Eligibility criteria: Inclusion Criteria:

* Hospitalized with COVID-19 pneumonia confirmed per WHO criteria (including a positive PCR of any specimen; e.g., respiratory, blood, urine, stool, other bodily fluid) and evidenced by chest X-ray or CT scan
* SPO2 \</=93% or PaO2/FiO2 \<300 mmHg

Exclusion Criteria:

* Known severe allergic reactions to TCZ or other monoclonal antibodies
* 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
* Have received oral anti-rejection or immunomodulatory drugs (including TCZ) with the past 3 months
* Participating in other drug clinical trials (participation in COVID-19 anti-viral trials may be permitted if approved by Medical Monitor)
* Pregnant or breastfeeding, or positive pregnancy test in a pre-dose examination
* Treatment with an investigational drug within 5 half-lives or 30 days (whichever is longer) of randomization (investigational COVID-19 antivirals may be permitted if approved by Medial Monitor)
* Any serious medical condition or abnormality of clinical laboratory tests that, in the investigator's judgment, precludes the patient's safe participation in and completion of the study
* Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \> 10 x upper limit of normal (ULN) detected within 24 hours at screening (per local lab)
* Absolute neutrophil count (ANC) \< 1000/mL at screening (per local lab)
* Platelet count \< 50,000/mL at screening (per local lab)

Primary outcomes:
measure: Clinical Status Assessed Using a 7-Category Ordinal Scale at Day 28 (Week 4)
timeFrame: Day 28
Secondary outcomes:
measure: Time to Clinical Improvement (TTCI), Defined as a National Early Warning Score 2 (NEWS2) of </= 2 Maintained for 24 Hours
timeFrame: Up to Day 28
measure: Time to Improvement of at Least 2 Categories Relative to Baseline on a 7-Category Ordinal Scale of Clinical Status
timeFrame: Up to Day 28
measure: Time to Hospital Discharge or "Ready for Discharge"
timeFrame: Up to Day 28
measure: Incidence of Mechanical Ventilation by Day 28
timeFrame: Up to Day 28
measure: Ventilator-Free Days to Day 28
timeFrame: Up to Day 28
measure: Incidence of Intensive Care Unit (ICU) Stay by Day 28 (Week 4)
timeFrame: Up to Day 28
measure: Duration of ICU Stay to Day 28 (Week 4)
timeFrame: Up to Day 28
measure: Clinical Status Assessed Using a 7-Category Ordinal Scale at Day 14
timeFrame: Day 14
measure: Time to Clinical Failure to Day 28 (Week 4)
timeFrame: Up to Day 28
measure: Mortality Rate at Day 28 (Week 4)
timeFrame: Day 28
measure: Time to Recovery to Day 28 (Week 4)
timeFrame: Up to Day 28
measure: Duration of Supplemental Oxygen to Day 28 (Week 4)
timeFrame: Up to Day 28
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: University of California San Diego
state: California
city: La Mesa
country: United States
facility: eStudySite
state: California
city: Los Angeles
country: United States
facility: David Geffen School of Medicine UCLA
state: California
city: Stanford
country: United States
facility: Stanford University
state: California
city: Denver
country: United States
facility: Denver Health Medical Center
state: Colorado
city: Miami
country: United States
facility: University of Miami Miller School of Medicine
state: Florida
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Baton Rouge
country: United States
facility: Ochsner Clinic Foundation
state: Louisiana
city: Springfield
country: United States
facility: Baystate Health System
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic - PPDS
state: Minnesota
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: New Brunswick
country: United States
facility: Robert Wood Johnson University Hospital/Rutgers
state: New Jersey
city: Bronx
country: United States
facility: James J Peters Veterans Administration Medical Center - NAVREF
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation; Pulmonary, Allergy & Critical Care Medicine
state: Ohio
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
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: Saint George
country: United States
facility: Intermountain Medical Group
state: Utah
city: Salt Lake City
country: United States
facility: Intermountain LDS Hospital
state: Utah
city: Kirkland
country: United States
facility: Evergreen Health Infectious Disease
state: Washington
city: Seattle
country: United States
facility: Swedish Hospital Medical Center
state: Washington
city: Hamilton
country: Canada
facility: Hamilton General Hospital; Pharmacy
state: Ontario
city: Hamilton
country: Canada
facility: St. Joseph's Healthcare Hamilton
state: Ontario
city: Toronto
country: Canada
facility: University Health Network
state: Ontario
city: Montreal
country: Canada
facility: Clinical Research Institute of Montreal
state: Quebec
city: Copenhagen
country: Denmark
facility: Rigshospitalet Copenhagen University Hospital
city: Hvidovre
country: Denmark
facility: Hvidovre Hospital
city: Odense C
country: Denmark
facility: Odense Universitetshospital
city: Roskilde
country: Denmark
facility: Sjællands Universitetshospital, Roskilde
city: La Roche Sur Yon
country: France
facility: Centre Hospitalier Departemental de Vendee
city: Limoges
country: France
facility: Centre Hospitalier et Universitaire de Limoges
city: Lyon
country: France
facility: Hôpital de La Croix Rousse
city: Nantes
country: France
facility: Hotel Dieu - Nantes
city: Paris
country: France
facility: Hopital de la Pitie Salpetriere
city: Paris
country: France
facility: HOPITAL COCHIN university hospital
city: Tours
country: France
facility: CHRU de Tours, Pharmacie
city: Dusseldorf
country: Germany
facility: Universitatsklinikum Dusseldorf
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: Köln
country: Germany
facility: Universitätsklinikum Köln; Innere Medizin I; Onkologie, Hämatologie
city: Munchen
country: Germany
facility: LMU Klinikum der Universitat Munchen
city: Monza MI
country: Italy
facility: Azienda Ospedaliera San Gerardo di Monza
state: Lombardia
city: Pavia
country: Italy
facility: Fondazione IRCCS Policlinico San Matteo di Pavia; S.S. Fisiopatologia Respiratoria
state: Lombardia
city: Breda
country: Netherlands
facility: Amphia Ziekenhuis
city: Nieuwegein
country: Netherlands
facility: St. Antonius Ziekenhuis Nieuwegein
city: Rotterdam
country: Netherlands
facility: Erasmus MC
city: Utrecht
country: Netherlands
facility: Universitair Medisch Centrum Utrecht
city: Hospitalet de Llobregat
country: Spain
facility: Hospital Universitario de Bellvitge
state: Barcelona
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Maranon
city: Madrid
country: Spain
facility: Hospital Universitario HM Sanchinarro-CIOCC
city: Glasgow
country: United Kingdom
facility: Greater Glasgow and Clyde Health Board
city: Leeds
country: United Kingdom
facility: Leeds Teaching Hospitals NHS Trust
city: London
country: United Kingdom
facility: University College Hospital
city: London
country: United Kingdom
facility: Royal Free Hospital
city: London
country: United Kingdom
facility: St George's Clinical Research Facility
city: London
country: United Kingdom
facility: Imperial College London
city: Manchester
country: United Kingdom
facility: North Manchester General Hospital
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Rosas IO, Brau N, Waters M, Go RC, Malhotra A, Hunter BD, Bhagani S, Skiest D, Savic S, Douglas IS, Garcia-Diaz J, Aziz MS, Cooper N, Youngstein T, Sorbo LD, Zerda DJ, Ustianowski A, Gracian AC, Blyth KG, Carratala J, Francois B, Benfield T, Haslem D, Bonfanti P, van der Leest CH, Rohatgi N, Wiese L, Luyt CE, Bauer RN, Cai F, Lee IT, Matharu B, Metcalf L, Wildum S, Graham E, Tsai L, Bao M. Tocilizumab in patients hospitalised with COVID-19 pneumonia: Efficacy, safety, viral clearance, and antibody response from a randomised controlled trial (COVACTA). EClinicalMedicine. 2022 May;47:101409. doi: 10.1016/j.eclinm.2022.101409. Epub 2022 Apr 21.
citation: Tom J, Bao M, Tsai L, Qamra A, Summers D, Carrasco-Triguero M, McBride J, Rosenberger CM, Lin CJF, Stubbings W, Blyth KG, Carratala J, Francois B, Benfield T, Haslem D, Bonfanti P, van der Leest CH, Rohatgi N, Wiese L, Luyt CE, Kheradmand F, Rosas IO, Cai F. Prognostic and Predictive Biomarkers in Patients With Coronavirus Disease 2019 Treated With Tocilizumab in a Randomized Controlled Trial. Crit Care Med. 2022 Mar 1;50(3):398-409. doi: 10.1097/CCM.0000000000005229.
citation: Rosas IO, Brau N, Waters M, Go RC, Hunter BD, Bhagani S, Skiest D, Aziz MS, Cooper N, Douglas IS, Savic S, Youngstein T, Del Sorbo L, Cubillo Gracian A, De La Zerda DJ, Ustianowski A, Bao M, Dimonaco S, Graham E, Matharu B, Spotswood H, Tsai L, Malhotra A. Tocilizumab in Hospitalized Patients with Severe Covid-19 Pneumonia. N Engl J Med. 2021 Apr 22;384(16):1503-1516. doi: 10.1056/NEJMoa2028700. Epub 2021 Feb 25.