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COVID-19 PneumoniaPhase 3COVACTANCT04320615

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

A Phase 3 study testing Tocilizumab (TCZ) in people with COVID-19 Pneumonia, run by Hoffmann-La Roche at 62 sites in 9 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
COVID-19 Pneumonia
What is being tested?
Tocilizumab (TCZ)
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
452 participants
Where
62 sitesin 9 countries
Study dates
3 Apr 2020to 28 Jul 2020
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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)
Show all 12Show fewer
  • 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 locations and contacts

62 sites in 9 countries.

62 sites in 9 countries

United States23 sites

  • Ochsner Clinic Foundation

    Baton Rouge, Louisiana, 70809

  • Rush University Medical Center

    Chicago, Illinois, 60612

  • University of Chicago

    Chicago, Illinois, 60637

  • Cleveland Clinic Foundation; Pulmonary, Allergy & Critical Care Medicine

    Cleveland, Ohio, 44195

  • Denver Health Medical Center

    Denver, Colorado, 80204

  • Duke University Medical Center

    Durham, North Carolina, 27710

  • Hackensack University Medical Center

    Hackensack, New Jersey, 07601

  • Baylor St. Luke's Medical Center

    Houston, Texas, 77030

  • Ben Taub General Hospital - HCHD

    Houston, Texas, 77030

  • Evergreen Health Infectious Disease

    Kirkland, Washington, 98034

  • University of California San Diego

    La Jolla, California, 92093

  • eStudySite

    La Mesa, California, 91942

  • David Geffen School of Medicine UCLA

    Los Angeles, California, 90095

  • University of Miami Miller School of Medicine

    Miami, Florida, 33136

  • Robert Wood Johnson University Hospital/Rutgers

    New Brunswick, New Jersey, 08901

  • Thomas Jefferson University

    Philadelphia, Pennsylvania, 19107

  • Mayo Clinic - PPDS

    Rochester, Minnesota, 55905

  • Intermountain LDS Hospital

    Salt Lake City, Utah, 84143

  • Swedish Hospital Medical Center

    Seattle, Washington, 98104

  • Baystate Health System

    Springfield, Massachusetts, 01199

  • Intermountain Medical Group

    St. George, Utah, 84770

  • Stanford University

    Stanford, California, 94305

  • James J Peters Veterans Administration Medical Center - NAVREF

    The Bronx, New York, 10468

Other trials in United States

France7 sites

  • Centre Hospitalier Departemental de Vendee

    La Roche-sur-Yon, 85925

  • Centre Hospitalier et Universitaire de Limoges

    Limoges, 87042

  • Hôpital de La Croix Rousse

    Lyon, 69004

  • Hotel Dieu - Nantes

    Nantes, 44093

  • Hopital de la Pitie Salpetriere

    Paris, 75013

  • HOPITAL COCHIN university hospital

    Paris, 75014

  • CHRU de Tours, Pharmacie

    Tours, 37044

Other trials in France

Spain7 sites

  • Hospital Universitari Vall d'Hebron

    Barcelona, 08035

  • Hospital Clinic de Barcelona

    Barcelona, 08036

  • Hospital Universitario de Bellvitge

    L'Hospitalet de Llobregat, Barcelona, 08907

  • Hospital Universitario La Paz

    Madrid, 28034

  • Hospital Universitario Ramon y Cajal

    Madrid, 28034

  • Hospital General Universitario Gregorio Maranon

    Madrid, 28040

  • Hospital Universitario HM Sanchinarro-CIOCC

    Madrid, 28050

Other trials in Spain

United Kingdom7 sites

  • Greater Glasgow and Clyde Health Board

    Glasgow, G12 8TA

  • Leeds Teaching Hospitals NHS Trust

    Leeds, LS9 7AU

  • University College Hospital

    London, NW1 2BU

  • Royal Free Hospital

    London, NW3 2QS

  • St George's Clinical Research Facility

    London, SW17 0RE

  • Imperial College London

    London, W6 8RF

  • North Manchester General Hospital

    Manchester, M8 5RB

Other trials in United Kingdom

Canada4 sites

  • Hamilton General Hospital; Pharmacy

    Hamilton, Ontario, L8L 2X2

  • St. Joseph's Healthcare Hamilton

    Hamilton, Ontario, L8N 4A6

  • Clinical Research Institute of Montreal

    Montreal, Quebec, H2W 1R7

  • University Health Network

    Toronto, Ontario, M5G2M9

Other trials in Canada

Denmark4 sites

  • Rigshospitalet Copenhagen University Hospital

    Copenhagen, DK-2100

  • Hvidovre Hospital

    Hvidovre, DK-2650

  • Odense Universitetshospital

    Odense C, 5000

  • Sjællands Universitetshospital, Roskilde

    Roskilde, 4000

Other trials in Denmark

Germany4 sites

  • Universitätsklinikum Köln; Innere Medizin I; Onkologie, Hämatologie

    Cologne, 50931

  • Universitatsklinikum Dusseldorf

    Düsseldorf, 40225

  • Medizinische Hochschule Hannover

    Hanover, 30625

  • LMU Klinikum der Universitat Munchen

    München, 80337

Other trials in Germany

Netherlands4 sites

  • Amphia Ziekenhuis

    Breda, 4819 EV

  • St. Antonius Ziekenhuis Nieuwegein

    Nieuwegein, 3435 CM

  • Erasmus MC

    Rotterdam, 3015 GD

  • Universitair Medisch Centrum Utrecht

    Utrecht, 3584 CX

Other trials in Netherlands

Italy2 sites

  • Azienda Ospedaliera San Gerardo di Monza

    Monza MI, Lombardy, 20900

  • Fondazione IRCCS Policlinico San Matteo di Pavia; S.S. Fisiopatologia Respiratoria

    Pavia, Lombardy, 27100

Other trials in Italy

About this study

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

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.

Being tested
Tocilizumab (TCZ), Placebo

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Tocilizumab (TCZ)Drug

    Participants will receive 1 dose of IV TCZ. 1 additional dose may be given if clinical symptoms worsen or show no improvement.

  • PlaceboDrug

    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.

Study groups in NCT04320615
Study groupRoleWhat they receive
Tocilizumab (TCZ) ArmExperimentalParticipants 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.
Receives: Drug: Tocilizumab (TCZ)
Placebo ArmPlacebo comparatorParticipants 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.
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Clinical Status Assessed Using a 7-Category Ordinal Scale at Day 28 (Week 4)

    Clinical status was assessed using a 7-category ordinal scale:

    1. - Discharged (or "ready for discharge")
    2. - Non- intensive care unit (ICU) hospital ward (or "ready for hospital ward") not requiring supplemental oxygen
    3. - Non-ICU hospital ward (or "ready for hospital ward") requiring supplemental oxygen
    4. - ICU or non-ICU hospital ward, requiring non-invasive ventilation or high-flow oxygen
    5. - ICU, requiring intubation and mechanical ventilation
    6. - ICU, requiring extracorporeal membrane oxygenation (ECMO) or mechanical ventilation and additional organ support
    7. - Death

    Measured: Day 28

Secondary outcomes (12)

  1. 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.

    Measured: Up to Day 28

  2. 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.

    Measured: Up to Day 28

  3. 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 </=2L supplemental oxygen) Participants who died were censored at Day 28.

    Measured: Up to Day 28

  4. Incidence of Mechanical Ventilation by Day 28

    Participants who died by Day 28 were assumed to have required mechanical ventilation.

    Measured: Up to Day 28

  5. Ventilator-Free Days to Day 28

    Participants who died by Day 28 were assigned 0 ventilator-free days.

    Measured: Up to Day 28

  6. 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.

    Measured: Up to Day 28

  7. 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.

    Measured: Up to Day 28

  8. Clinical Status Assessed Using a 7-Category Ordinal Scale at Day 14

    Clinical status was assessed using a 7-category ordinal scale:

    1. - Discharged (or "ready for discharge")
    2. - Non- intensive care unit (ICU) hospital ward (or "ready for hospital ward") not requiring supplemental oxygen
    3. - Non-ICU hospital ward (or "ready for hospital ward") requiring supplemental oxygen
    4. - ICU or non-ICU hospital ward, requiring non-invasive ventilation or high-flow oxygen
    5. - ICU, requiring intubation and mechanical ventilation
    6. - ICU, requiring extracorporeal membrane oxygenation (ECMO) or mechanical ventilation and additional organ support
    7. - Death

    Measured: Day 14

  9. 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.

    Measured: Up to Day 28

  10. Mortality Rate at Day 28 (Week 4)

    Measured: Day 28

  11. 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 </= 2L supplemental oxygen) or non-ICU hospital ward or "ready for hospital ward" not requiring supplemental oxygen. Participants who died were censored at Day 28.

    Measured: Up to Day 28

  12. 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.

    Measured: Up to Day 28

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Mar 2020
  2. Study start3 Apr 2020
  3. Primary completion24 Jun 2020
  4. Study completion28 Jul 2020

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
452 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04320615
Sponsor's protocol ID
WA42380
Other IDs
2020-001154-22
Acronym
COVACTA
Status last verified
Jun 2021
First submitted
23 Mar 2020
Last updated
30 Jun 2021
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Qualified researchers may request access to individual patient level data through the clinical study data request platform https://vivli.org. Further details on Roche's criteria for eligible studies are available here: https://vivli.org. For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here: (https://www.roche.com/research\_and\_development/who\_we\_are\_how\_we\_work/clinical\_trials/our\_commitment\_to\_data\_sharing.htm

Publications

  • 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.

    PubMed 35475258

  • 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.

    PubMed 34612846

  • 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.

    PubMed 33631066

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Tocilizumab (TCZ) in people with COVID-19 Pneumonia, run by Hoffmann-La Roche at 62 sites in 9 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 30 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 62 sites in United States, France, Spain, United Kingdom, Canada and 4 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 30 Jun 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Clinical Status Assessed Using a 7-Category Ordinal Scale at Day 28 (Week 4) (time frame: Day 28). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04320615, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jun 2021.

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