A Study to Evaluate the Safety and Efficacy of Tocilizumab in Patients With Severe COVID-19 Pneumonia

COVID-19 Pneumonia Clinical Trial

— COVACTA  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04320615
• Other study ID #: WA42380
• Secondary ID: 2020-001154-22
• Status: Completed
• Phase: Phase 3
• Start date: April 3, 2020
• Est. completion date: July 28, 2020

Study information

• Verified date: June 2021
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 452
• Est. completion date: July 28, 2020
• Est. primary completion date: June 24, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• COVID-19 Pneumonia
• Pneumonia

Intervention

Drug:
• Tocilizumab (TCZ)
Participants will receive 1 dose of IV TCZ. 1 additional dose may be given if clinical symptoms worsen or show no improvement.
• Placebo
Participants will receive 1 dose of IV placebo matched to TCZ. Up to 1 additional dose may be given if clinical symptoms worsen or show no improvement.

Locations

Country	Name	City	State
Canada	Hamilton General Hospital; Pharmacy	Hamilton	Ontario
Canada	St. Joseph's Healthcare Hamilton	Hamilton	Ontario
Canada	Clinical Research Institute of Montreal	Montreal	Quebec
Canada	University Health Network	Toronto	Ontario
Denmark	Rigshospitalet Copenhagen University Hospital	Copenhagen
Denmark	Hvidovre Hospital	Hvidovre
Denmark	Odense Universitetshospital	Odense C
Denmark	Sjællands Universitetshospital, Roskilde	Roskilde
France	Centre Hospitalier Departemental de Vendee	La Roche Sur Yon
France	Centre Hospitalier et Universitaire de Limoges	Limoges
France	Hôpital de La Croix Rousse	Lyon
France	Hotel Dieu - Nantes	Nantes
France	HOPITAL COCHIN university hospital	Paris
France	Hopital de la Pitie Salpetriere	Paris
France	CHRU de Tours, Pharmacie	Tours
Germany	Universitatsklinikum Dusseldorf	Dusseldorf
Germany	Medizinische Hochschule Hannover	Hannover
Germany	Universitätsklinikum Köln; Innere Medizin I; Onkologie, Hämatologie	Köln
Germany	LMU Klinikum der Universitat Munchen	Munchen
Italy	Azienda Ospedaliera San Gerardo di Monza	Monza MI	Lombardia
Italy	Fondazione IRCCS Policlinico San Matteo di Pavia; S.S. Fisiopatologia Respiratoria	Pavia	Lombardia
Netherlands	Amphia Ziekenhuis	Breda
Netherlands	St. Antonius Ziekenhuis Nieuwegein	Nieuwegein
Netherlands	Erasmus MC	Rotterdam
Netherlands	Universitair Medisch Centrum Utrecht	Utrecht
Spain	Hospital Clinic de Barcelona	Barcelona
Spain	Hospital Universitari Vall d'Hebron	Barcelona
Spain	Hospital Universitario de Bellvitge	Hospitalet de Llobregat	Barcelona
Spain	Hospital General Universitario Gregorio Maranon	Madrid
Spain	Hospital Universitario HM Sanchinarro-CIOCC	Madrid
Spain	Hospital Universitario La Paz	Madrid
Spain	Hospital Universitario Ramon y Cajal	Madrid
United Kingdom	Greater Glasgow and Clyde Health Board	Glasgow
United Kingdom	Leeds Teaching Hospitals NHS Trust	Leeds
United Kingdom	Imperial College London	London
United Kingdom	Royal Free Hospital	London
United Kingdom	St George's Clinical Research Facility	London
United Kingdom	University College Hospital	London
United Kingdom	North Manchester General Hospital	Manchester
United States	Ochsner Clinic Foundation	Baton Rouge	Louisiana
United States	James J Peters Veterans Administration Medical Center - NAVREF	Bronx	New York
United States	Rush University Medical Center	Chicago	Illinois
United States	University of Chicago	Chicago	Illinois
United States	Cleveland Clinic Foundation; Pulmonary, Allergy & Critical Care Medicine	Cleveland	Ohio
United States	Denver Health Medical Center	Denver	Colorado
United States	Duke University Medical Center	Durham	North Carolina
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	Baylor St. Luke's Medical Center	Houston	Texas
United States	Ben Taub General Hospital - HCHD	Houston	Texas
United States	Evergreen Health Infectious Disease	Kirkland	Washington
United States	University of California San Diego	La Jolla	California
United States	eStudySite	La Mesa	California
United States	David Geffen School of Medicine UCLA	Los Angeles	California
United States	University of Miami Miller School of Medicine	Miami	Florida
United States	Robert Wood Johnson University Hospital/Rutgers	New Brunswick	New Jersey
United States	Thomas Jefferson University	Philadelphia	Pennsylvania
United States	Mayo Clinic - PPDS	Rochester	Minnesota
United States	Intermountain Medical Group	Saint George	Utah
United States	Intermountain LDS Hospital	Salt Lake City	Utah
United States	Swedish Hospital Medical Center	Seattle	Washington
United States	Baystate Health System	Springfield	Massachusetts
United States	Stanford University	Stanford	California

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Canada,  Denmark,  France,  Germany,  Italy,  Netherlands,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Clinical Status Assessed Using a 7-Category Ordinal Scale at Day 28 (Week 4)	Clinical status was assessed using a 7-category ordinal scale: - Discharged (or "ready for discharge"); - 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; - Death	Day 28
Secondary	Time to Clinical Improvement (TTCI), Defined as a National Early Warning Score 2 (NEWS2) of </= 2 Maintained for 24 Hours	Defined as time from first dose of study drug to at least two NEWS2 assessments with a score of <=2 covering a span of at least 21.5 hours, with a maximum of 26.5 hours between the first and last of these assessments and no assessments with a score >2 in between. If one of the components of the NEWS2 score was missing at a particular time point, then the NEWS2 score was not calculated. Participants who died were censored at Day 28.	Up to Day 28
Secondary	Time to Improvement of at Least 2 Categories Relative to Baseline on a 7-Category Ordinal Scale of Clinical Status	Time to improvement for this outcome measure was defined as the days from the first dose of study drug to when at least a 2-category improvement in clinical status (based on a 7-category ordinal scale) is observed. Participants who died were censored at Day 28.	Up to Day 28
Secondary	Time to Hospital Discharge or "Ready for Discharge"	Time to Hospital Discharge was defined as the time from the first dose of study drug to hospital discharge or "ready for discharge" (normal body temperature and respiratory rate, and stable oxygen saturation on ambient air or	Up to Day 28
Secondary	Incidence of Mechanical Ventilation by Day 28	Participants who died by Day 28 were assumed to have required mechanical ventilation.	Up to Day 28
Secondary	Ventilator-Free Days to Day 28	Participants who died by Day 28 were assigned 0 ventilator-free days.	Up to Day 28
Secondary	Incidence of Intensive Care Unit (ICU) Stay by Day 28 (Week 4)	Participants who died by Day 28 were assumed to have required an ICU stay.	Up to Day 28
Secondary	Duration of ICU Stay to Day 28 (Week 4)	Participants who died by Day 28 were assigned a duration from the first dose of study drug to Day 28 at hour 23:59:59.	Up to Day 28
Secondary	Clinical Status Assessed Using a 7-Category Ordinal Scale at Day 14	Clinical status was assessed using a 7-category ordinal scale: - Discharged (or "ready for discharge"); - 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; - Death	Day 14
Secondary	Time to Clinical Failure to Day 28 (Week 4)	Time to clinical failure was defined as the number of days from the first dose of study drug to the first occurrence on study of death, mechanical ventilation, ICU admission, or study withdrawal prior to discharge, whichever occurs first.	Up to Day 28
Secondary	Mortality Rate at Day 28 (Week 4)		Day 28
Secondary	Time to Recovery to Day 28 (Week 4)	Time to recovery was defined as the number of days from the first dose of study drug to hospital discharge or "ready for discharge" (normal body temperature and respiratory rate, and stable oxygen saturation on ambient air or	Up to Day 28
Secondary	Duration of Supplemental Oxygen to Day 28 (Week 4)	Participants who died by Day 28 were assigned a duration of 28 days of supplemental oxygen.	Up to Day 28