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

NCT04320615 | Completed Phase 3 Results FDA Drug

• 2 other identifiers: WA423802020-001154-22
• Study Type: interventional
• Target: 452
• Locations: 9 countries
• Sites: 62

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.

Conditions

COVID-19 Pneumonia

Outcome Measures

Primary Outcomes (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

  Day 28

Secondary Outcomes (12)

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

  Up to Day 28

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

  Up to Day 28

• Time to Hospital Discharge or "Ready for Discharge"

  Up to Day 28

• Incidence of Mechanical Ventilation by Day 28

  Up to Day 28

• Ventilator-Free Days to Day 28

  Up to Day 28

Study Arms (2)

Tocilizumab (TCZ) Arm

EXPERIMENTAL

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)

Placebo Arm

PLACEBO COMPARATOR

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

Interventions

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.

Tocilizumab (TCZ) Arm

Placebo DRUG

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.

Placebo Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (62)

University of California San Diego

La Jolla, California, 92093, United States

Location

eStudySite

La Mesa, California, 91942, United States

Location

David Geffen School of Medicine UCLA

Los Angeles, California, 90095, United States

Location

Stanford University

Stanford, California, 94305, United States

Location

Denver Health Medical Center

Denver, Colorado, 80204, United States

Location

University of Miami Miller School of Medicine

Miami, Florida, 33136, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

Ochsner Clinic Foundation

Baton Rouge, Louisiana, 70809, United States

Location

Baystate Health System

Springfield, Massachusetts, 01199, United States

Location

Mayo Clinic - PPDS

Rochester, Minnesota, 55905, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Robert Wood Johnson University Hospital/Rutgers

New Brunswick, New Jersey, 08901, United States

Location

James J Peters Veterans Administration Medical Center - NAVREF

The Bronx, New York, 10468, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Cleveland Clinic Foundation; Pulmonary, Allergy & Critical Care Medicine

Cleveland, Ohio, 44195, United States

Location

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

Baylor St. Luke's Medical Center

Houston, Texas, 77030, United States

Location

Ben Taub General Hospital - HCHD

Houston, Texas, 77030, United States

Location

Intermountain LDS Hospital

Salt Lake City, Utah, 84143, United States

Location

Intermountain Medical Group

St. George, Utah, 84770, United States

Location

Evergreen Health Infectious Disease

Kirkland, Washington, 98034, United States

Location

Swedish Hospital Medical Center

Seattle, Washington, 98104, United States

Location

Hamilton General Hospital; Pharmacy

Hamilton, Ontario, L8L 2X2, Canada

Location

St. Joseph's Healthcare Hamilton

Hamilton, Ontario, L8N 4A6, Canada

Location

University Health Network

Toronto, Ontario, M5G2M9, Canada

Location

Clinical Research Institute of Montreal

Montreal, Quebec, H2W 1R7, Canada

Location

Rigshospitalet Copenhagen University Hospital

Copenhagen, DK-2100, Denmark

Location

Hvidovre Hospital

Hvidovre, DK-2650, Denmark

Location

Odense Universitetshospital

Odense C, 5000, Denmark

Location

Sjællands Universitetshospital, Roskilde

Roskilde, 4000, Denmark

Location

Centre Hospitalier Departemental de Vendee

La Roche-sur-Yon, 85925, France

Location

Centre Hospitalier et Universitaire de Limoges

Limoges, 87042, France

Location

Hôpital de La Croix Rousse

Lyon, 69004, France

Location

Hotel Dieu - Nantes

Nantes, 44093, France

Location

Hopital de la Pitie Salpetriere

Paris, 75013, France

Location

HOPITAL COCHIN university hospital

Paris, 75014, France

Location

CHRU de Tours, Pharmacie

Tours, 37044, France

Location

Universitätsklinikum Köln; Innere Medizin I; Onkologie, Hämatologie

Cologne, 50931, Germany

Location

Universitatsklinikum Dusseldorf

Düsseldorf, 40225, Germany

Location

Medizinische Hochschule Hannover

Hanover, 30625, Germany

Location

LMU Klinikum der Universitat Munchen

München, 80337, Germany

Location

Azienda Ospedaliera San Gerardo di Monza

Monza MI, Lombardy, 20900, Italy

Location

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

Pavia, Lombardy, 27100, Italy

Location

Amphia Ziekenhuis

Breda, 4819 EV, Netherlands

Location

St. Antonius Ziekenhuis Nieuwegein

Nieuwegein, 3435 CM, Netherlands

Location

Erasmus MC

Rotterdam, 3015 GD, Netherlands

Location

Universitair Medisch Centrum Utrecht

Utrecht, 3584 CX, Netherlands

Location

Hospital Universitario de Bellvitge

L'Hospitalet de Llobregat, Barcelona, 08907, Spain

Location

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Clinic de Barcelona

Barcelona, 08036, Spain

Location

Hospital Universitario La Paz

Madrid, 28034, Spain

Location

Hospital Universitario Ramon y Cajal

Madrid, 28034, Spain

Location

Hospital General Universitario Gregorio Maranon

Madrid, 28040, Spain

Location

Hospital Universitario HM Sanchinarro-CIOCC

Madrid, 28050, Spain

Location

Greater Glasgow and Clyde Health Board

Glasgow, G12 8TA, United Kingdom

Location

Leeds Teaching Hospitals NHS Trust

Leeds, LS9 7AU, United Kingdom

Location

University College Hospital

London, NW1 2BU, United Kingdom

Location

Royal Free Hospital

London, NW3 2QS, United Kingdom

Location

St George's Clinical Research Facility

London, SW17 0RE, United Kingdom

Location

Imperial College London

London, W6 8RF, United Kingdom

Location

North Manchester General Hospital

Manchester, M8 5RB, United Kingdom

Location

Related Publications (3)

• 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.

  PMID: 35475258 DERIVED

• 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.

  PMID: 34612846 DERIVED

• 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.

  PMID: 33631066 DERIVED

MeSH Terms

Interventions

tocilizumab

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

1-800-821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 23, 2020
• First Posted: March 25, 2020
• Study Start: April 3, 2020
• Primary Completion: June 24, 2020
• Study Completion: July 28, 2020
• Last Updated: June 30, 2021
• Results First Posted: June 30, 2021

Record last verified: 2021-06

Data Sharing

• IPD Sharing: Will share

Locations

FR (7); ES (7); IT (2); GB (7); CA (4); DK (4); DE (4); NL (4); US (23)