A Study to Evaluate the Efficacy and Safety of Tocilizumab in Hospitalized Participants With COVID-19 Pneumonia (EMPACTA)

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

This study (EMPACTA) will a) evaluate the efficacy and safety of tocilizumab (TCZ) compared with a placebo in combination with standard of care (SOC) in hospitalized participants with COVID-19 pneumonia, and b) include an optional long-term extension for eligible participants to explore the long-term sequelae of resolved COVID-19 pneumonia.

Study Overview

• Status: Completed
• Conditions: COVID-19 Pneumonia
• Intervention / Treatment: Drug: Placebo; Drug: Tocilizumab

• Study Type: Interventional
• Enrollment (Actual): 377
• Phase: Phase 3

Contacts and Locations

Study Locations

• Brazil
  • SP
    • Campinas, SP, Brazil, 13060-904
      • Hospital E Maternidade Celso Pierro PUCCAMP
    • Sao Bernardo Do Campo, SP, Brazil, 09715-090
      • Centro Multidisciplinar de Estudos Clínicos CEMEC FMABC
    • Sao Paulo, SP, Brazil, 03325-050
      • BR Trials - Pesquisa Clínica
• Kenya
  • Nairobi, Kenya, 30270-00100
    • Aga Khan University Hospital
• Mexico
  • Culiacan, Mexico, 80230
    • Hospital General de Culiacan
  • Mexico, Mexico
    • Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
• Peru
  • Jesus Maria, Peru, Lima 11
    • Hospital Militar Central
  • Lima, Peru, Lima 29
    • Hospital Maria Auxiliadora
  • Lima, Peru, Lima 10
    • Hospital Nacional Hipolito; Unanue
  • Lima, Peru, 31
    • Hospital Nacional Cayetano Heredia
  • Lima, Peru, 15003
    • Hospital Nacional Sergio E. Bernales
• South Africa
  • George, South Africa, 6259
    • George Provincial Hospital
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85006
      • Banner - University Medical Center Phoenix; In-Patient Pharmacy
    • Tucson, Arizona, United States, 85724
      • Univ of AZ Coll of Med
  • California
    • El Centro, California, United States, 92243
      • El Centro Regional Medical Center
    • La Mesa, California, United States, 91942
      • eStudySite
    • Oakland, California, United States, 94602
      • Highland Hospital Oakland
    • Orange, California, United States, 92563
      • St. Joseph's Hospital
    • San Leandro, California, United States, 94578
      • San Leandro Hospital; Inpatient Pharmacy
  • Florida
    • Hialeah, Florida, United States, 33012
      • Larkin Community Hospital Palm Springs Campus (Hialeah)
    • Miami, Florida, United States, 33125
      • Miami Veterans Administration Healthcare System - NAVREF
    • Miami, Florida, United States, 33125
      • University of Miami Pulmonary
    • South Miami, Florida, United States, 33143
      • Larkin Community Hospital
  • Idaho
    • Boise, Idaho, United States, 83712
      • St. Lukes Boise Medical Center
  • Louisiana
    • New Orleans, Louisiana, United States, 70121
      • Ochsner Clinic
  • Maryland
    • Germantown, Maryland, United States, 20876
      • Holy Cross Germantown Hospital
    • Silver Spring, Maryland, United States, 20910
      • Holy Cross Hospital
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health System
  • New Jersey
    • Paterson, New Jersey, United States, 07503
      • St. Joseph's Regional Medical Center
  • New Mexico
    • Farmington, New Mexico, United States, 87401
      • San Juan Oncology Associates
  • New York
    • Bronx, New York, United States, 10457
      • St. Barnabas Hospital
    • Brooklyn, New York, United States, 11203
      • SUNY Downstate Medical Center.
    • Elmhurst, New York, United States, 11373
      • Elmhurst Hospital Center
    • Flushing, New York, United States, 11355
      • Flushing Hospital
    • Jamaica, New York, United States, 11418
      • Jamaica Hospital Medical Center
    • New York, New York, United States, 10037
      • Harlem Hospital
    • Potsdam, New York, United States, 13676
      • Canton-Potsdam Hospital
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Novant Health Presbyterian Medical Center (Presbyterian Hospital)
    • Fayetteville, North Carolina, United States, 28304
      • Cape Fear Valley Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19140
      • Temple University Hospital
  • Texas
    • Harlingen, Texas, United States, 78550
      • Valley Baptist Medical Center
    • Houston, Texas, United States, 77030
      • Michael E DeBakey VA Medical Center
    • McAllen, Texas, United States, 78503
      • McAllen Medical Center
  • Virginia
    • Virginia Beach, Virginia, United States, 23462
      • Sentara Medical Group

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria

• Hospitalized
• COVID-19 pneumonia confirmed by a positive polymerase chain reaction (PCR) of any specimen and radiographic imaging
• SpO2 < 94% while on ambient air

Inclusion Criteria Specific to Long-Term Extension

• Participated in Study ML42528 (EMPACTA) (includes participants who completed or discontinued early from the main study)

Exclusion Criteria

• Known severe allergic reactions to TCZ or other monoclonal antibodies
• Require continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), or invasive mechanical ventilation
• 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
• Immunocompromised (besides well-controlled HIV) or on immunosuppressive therapy (except for steroids for COVID), advanced cancer
• Have received oral anti-rejection or immunomodulatory drugs (including TCZ) within the past 3 months
• Participating in another interleukin (IL)-6 antagonist clinical trial or other drug clinical trials (participation in COVID-19 anti-viral trials may be permitted if approved by Medical Monitor)
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 10 x upper limit of normal (ULN) detected within 24 hours at screening (according to local laboratory reference ranges)
• Absolute neutrophil count (ANC) < 1000/uL at screening (according to local laboratory reference ranges)
• Platelet count < 50,000/uL at screening (according to local laboratory reference ranges)
• 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 Medical 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
• Any history of Diverticulitis or GI perforation
• Use of systemic corticosteroids unless on a stable chronic dose

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo; Participants will receive one intravenous (IV) infusion of placebo, in addition to SOC. Up to one additional infusion may be given.	Drug: Placebo; Participants will receive one dose of IV placebo matched to TCZ. Up to one additional dose may be given.
EXPERIMENTAL: Tocilizumab; Participants will receive one IV infusion of TCZ in addition to SOC. Up to one additional infusion may be given.	Drug: Tocilizumab; Participants will receive one IV infusion of TCZ 8 mg/kg, with a maximum dose of 800 mg. Up to one additional dose may be given.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cumulative Proportion of Participants Who Died or Required Mechanical Ventilation by Day 28	Cumulative proportion is measured as a percentage of participants meeting the endpoint.	Up to Day 28

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Hospital Discharge or "Ready for Discharge" (as Evidenced by Normal Body Temperature and Respiratory Rate, and Stable Oxygen Saturation on Ambient Air or >/= 2 Liters (L) Supplemental Oxygen)		Up to Day 28
Time to Improvement of at Least 2 Categories Relative to Baseline on a 7-Category Ordinal Scale of Clinical Status	Clinical status was assessed using a 7-category ordinal scale: - Discharged (or "ready for discharge" as evidenced by normal body temperature and respiratory rate, and stable oxygen saturation on ambient air or </=2 liters supplemental oxygen); - 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	Up to Day 28
Time to Clinical Failure, Defined as the Time to Death, Mechanical Ventilation, ICU Admission, or Withdrawal (Whichever Occurred First)		Up to Day 28
Mortality Rate by Day 28		Up to Day 28
Clinical Status on 7-Category Ordinal Scale at Day 28	Clinical status was assessed using a 7-category ordinal scale: - Discharged (or "ready for discharge" as evidenced by normal body temperature and respiratory rate, and stable oxygen saturation on ambient air or </=2 liters supplemental oxygen); - 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
Percentage of Participants With Adverse Events		Up to Day 60

Collaborators and Investigators

• Sponsor: Genentech, Inc.

Publications and helpful links

General Publications

• Salama C, Han J, Yau L, Reiss WG, Kramer B, Neidhart JD, Criner GJ, Kaplan-Lewis E, Baden R, Pandit L, Cameron ML, Garcia-Diaz J, Chavez V, Mekebeb-Reuter M, Lima de Menezes F, Shah R, Gonzalez-Lara MF, Assman B, Freedman J, Mohan SV. Tocilizumab in Patients Hospitalized with Covid-19 Pneumonia. N Engl J Med. 2021 Jan 7;384(1):20-30. doi: 10.1056/NEJMoa2030340. Epub 2020 Dec 17.
• Tleyjeh IM. The Misleading "Pooled Effect Estimate" of Crude Data from Observational Studies at Critical Risk of Bias: The Case of Tocilizumab in Coronavirus Disease 2019 (COVID-19). Clin Infect Dis. 2021 Jun 15;72(12):e1154-e1155. doi: 10.1093/cid/ciaa1735. No abstract available.

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 14, 2020
• Primary Completion (ACTUAL): August 18, 2020
• Study Completion (ACTUAL): September 22, 2020

Study Registration Dates

• First Submitted: April 29, 2020
• First Submitted That Met QC Criteria: April 29, 2020
• First Posted (ACTUAL): May 1, 2020

Study Record Updates

• Last Update Posted (ACTUAL): February 10, 2023
• Last Update Submitted That Met QC Criteria: February 8, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Lung Diseases; COVID-19; Pneumonia
• Other Study ID Numbers: ML42528

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). 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).

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No