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A Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Safety and Efficacy of Tocilizumab in Patients With Severe COVID-19 Pneumonia

Trial Profile

A Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Safety and Efficacy of Tocilizumab in Patients With Severe COVID-19 Pneumonia

Status: Active, no longer recruiting
Phase of Trial: Phase III

Latest Information Update: 02 Jun 2020

At a glance

  • Drugs Tocilizumab (Primary)
  • Indications COVID 2019 infections; Pneumonia
  • Focus Registrational; Therapeutic Use
  • Acronyms COVACTA
  • Sponsors Roche
  • Most Recent Events

    • 28 May 2020 Status changed from recruiting to active, no longer recruiting.
    • 28 May 2020 According to an Roche media release, the data from the REMDACTA trial are designed to this study.
    • 28 May 2020 According to an Roche media release, the increase in original target of 330 patients to 450 patients will allow for even more robust data, while minimally extending the recruitment period. In addition, the protocol for COVACTA allows the inclusion of patients who are being treated with antivirals, including investigational antivirals.

Trial Overview

Purpose

This placebo-controlled Phase III study (COVACTA) is designed to evaluate the safety and efficacy of intravenous Actemra/RoActemra added to standard of care in adult patients hospitalised with severe COVID-19 pneumonia compared to placebo plus standard of care.
Patients will be followed for 60 days post-randomisation, and an interim analysis will be conducted to look for early evidence of efficacy.

Primary Endpoints

Clinical Status Assessed Using a 7-Category Ordinal Scale

time_frame: Day 28

Other Endpoints

Time to Clinical Improvement (TTCI), Defined as a National Early Warning Score 2 (NEWS2) of </= 2 Maintained for 24 Hours

time_frame: Up to 60 days

Time to Improvement of at Least 2 Categories Relative to Baseline on a 7-Category Ordinal Scale of Clinical Status

time_frame: Up to 60 days

Incidence of Mechanical Ventilation

time_frame: Up to 60 days

Ventilator-Free Days to Day 28

time_frame: Up to Day 28

Incidence of Intensive Care Unit (ICU) Stay

time_frame: Up to 60 days

Duration of ICU Stay

time_frame: Up to 60 days

Time to Clinical Failure

time_frame: From first dose to time of death, mechanical ventilation, ICU admission, or study withdrawal (whichever occurs first, for up to 60 days). If already in ICU on ventilation, failure = a one-category worsening on the ordinal scale, withdrawal, or death

Mortality Rate

time_frame: Days 7, 14, 21, 28, and 60

Time to Hospital Discharge

time_frame: Up to 60 days

Duration of Time on Supplemental Oxygen

time_frame: Up to 60 days

Percentage of Participants with Adverse Events

time_frame: Up to 60 days

COVID-19 (SARS-CoV-2) Viral Load Over Time

time_frame: Up to 60 days

Time to Reverse-Transcriptase Polymerase Chain Reaction (RT-PCR) Virus Negativity

time_frame: Up to 60 days

Proportion of Participants with Post-Treatment Infection

time_frame: Up to 60 days

Serum Concentration of IL-6

time_frame: Up to 60 days

Serum Concentration of sIL-6R

time_frame: Up to 60 days

Serum Concentration of Ferritin

time_frame: Up to 60 days

Serum Concentration of C-Reactive Protein (CRP)

time_frame: Up to 60 days

Serum Concentration of TCZ

time_frame: Up to 60 days [1]

Diseases Treated

Indication Qualifiers Patient Segments
COVID 2019 infections treatment -
Pneumonia treatment severe

Subjects

  • Subject Type patients
  • Number

    Planned: 450

    Actual: 450

  • Sex male & female
  • Age Group ≥ 18 years

Patient 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

Patient 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)

Trial Details

Identifiers

Identifier Owner
NCT04320615 ClinicalTrials.gov: US National Institutes of Health
EudraCT2020-001154-22 European Clinical Trials Database
WA42380 Roche

Organisations

  • Sponsors Roche
  • Affiliations Genentech; Roche

Trial Dates

  • Initiation Dates

    Planned : 03 Apr 2020

    Actual : 03 Apr 2020

  • Primary Completion Dates

    Planned : 31 Aug 2020

  • End Dates

    Planned : 30 Sep 2020

Other Details

  • Design double-blind; multicentre; parallel; prospective; randomised
  • Phase of Trial Phase III
  • Location Canada; Denmark; England; France; Germany; Ireland; Italy; Netherlands; Scotland; Spain; Sweden; Switzerland; United Kingdom; USA
  • Focus Registrational; Therapeutic Use

Interventions

Drugs Route Formulation
TocilizumabPrimary Drug Intravenous Infusion

Tocilizumab (TCZ) Arm

Participants will receive 1 intravenous (IV) infusion of TCZ, dosed at 8 mg/kg, up to a maximum dose 800 mg. Up to 1 additional dose may be given if clinical symptoms worsen or show no improvement.
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 Arm

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

Trial Centres

Investigators

Investigator Centre Name Trial Centre Country
Clinical Trials Hoffmann-La Roche
-
Reference Study ID Number: WA42380 www.roche.com/about_roche/roche_worldwide.htm
888-662-6728 global-roche-genentech-trials@gene.com
show details
-

Centres

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

Trial History

Event Date Event Type Comment
02 Jun 2020 Other trial event Last checked against Clinicaltrials.gov record. Updated 02 Jun 2020
28 May 2020 Status change - active, no longer recruiting Status changed from recruiting to active, no longer recruiting. Updated 02 Jun 2020
28 May 2020 Other trial event According to an Roche media release, the data from the REMDACTA trial are designed to this study. Updated 29 May 2020
28 May 2020 Other trial event According to an Roche media release, the increase in original target of 330 patients to 450 patients will allow for even more robust data, while minimally extending the recruitment period. In addition, the protocol for COVACTA allows the inclusion of patients who are being treated with antivirals, including investigational antivirals. Updated 29 May 2020
28 May 2020 Other trial event According to an Roche media release, this study is close to completing enrolment. The first patient in this study was randomised on April 3, 2020. Updated 29 May 2020
08 May 2020 Other trial event Last checked against European Clinical Trials Database record. Updated 08 May 2020
06 May 2020 Other trial event Planned number of patients changed from 330 to 450. Updated 06 May 2020
22 Apr 2020 Completion date Planned End Date changed from 30 Sep 2021 to 30 Sep 2020. Updated 27 Apr 2020
22 Apr 2020 Other trial event Planned primary completion date changed from 31 Aug 2021 to 31 Aug 2020. Updated 27 Apr 2020
22 Apr 2020 Other trial event According to a Roche media release, results from this study are expected in early summer. Updated 23 Apr 2020
06 Apr 2020 Status change - recruiting Status changed from not yet recruiting to recruiting. Updated 09 Apr 2020
06 Apr 2020 Other trial event New source identified and integrated (European Clinical Trials Database;EudraCT2020-001154-22). Updated 06 Apr 2020
27 Mar 2020 Other trial event New source identified and integrated (ClinicalTrials.gov record: NCT04320615). Updated 27 Mar 2020
23 Mar 2020 Status change - not yet recruiting Status changed from planning to not yet recruiting. Updated 27 Mar 2020
23 Mar 2020 Other trial event According to a Genentech media release, the U.S. Food and Drug Administration (FDA) has approved this trial. The company is moving forward to enroll as quickly as possible. Updated 24 Mar 2020
19 Mar 2020 Other trial event According to a Roche media release, an interim analysis will be conducted to look for early evidence of efficacy.This is the first global study of Actemra/RoActemra in this setting and is expected to begin enrolling as soon as possible in early April. Updated 19 Mar 2020
19 Mar 2020 Other trial event According to a Roche media release, the company is working with the FDA to initiate this Phase III clinical trial in collaboration with the Biomedical Advanced Research and Development Authority (BARDA), a part of the US Health and Human Services Office of the Assistant Secretary for Preparedness and Response (ASPR). Updated 19 Mar 2020
19 Mar 2020 New trial record New trial record Updated 19 Mar 2020

References

  1. ClinicalTrials.gov: US National Institutes of Health. Trial-Reg 2016;.

    Available from: URL: http://clinicaltrials.gov
  2. European Clinical Trials Database. Trial-Reg 2016;.

    Available from: URL: https://www.clinicaltrialsregister.eu
  3. Roche. Investor Update: Roche- 22 April 2020. Media-Rel 2020;.

    Media Release
  4. Roche. Roche initiates Phase III clinical trial of Actemra/RoActemra in hospitalised patients with severe COVID-19 pneumonia. Media-Rel 2020;.

    Media Release
  5. Roche. Roche initiates phase III clinical trial of Actemra/RoActemra plus remdesivir in hospitalised patients with severe COVID-19 pneumonia. Media-Rel 2020;.

    Media Release
  6. Genentech. Genentech Announces FDA Approval of Clinical Trial for Actemra to Treat Hospitalized Patients With Severe COVID-19 Pneumonia. Media-Rel 2020;.

    Media Release
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