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

COVID-19 Pneumonia Clinical Trial

— EMPACTA  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04372186
• Other study ID #: ML42528
• Status: Completed
• Phase: Phase 3
• Start date: May 14, 2020
• Est. completion date: September 22, 2020

Study information

• Verified date: February 2023
• Source: Genentech, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 377
• Est. completion date: September 22, 2020
• Est. primary completion date: August 18, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• COVID-19
• COVID-19 Pneumonia
• Pneumonia

Intervention

Drug:
• Placebo
Participants will receive one dose of IV placebo matched to TCZ. Up to one additional dose may be given.
• 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.

Locations

Country	Name	City	State
Brazil	Hospital E Maternidade Celso Pierro PUCCAMP	Campinas	SP
Brazil	Centro Multidisciplinar de Estudos Clínicos CEMEC FMABC	Sao Bernardo Do Campo	SP
Brazil	BR Trials - Pesquisa Clínica	Sao Paulo	SP
Kenya	Aga Khan University Hospital	Nairobi
Mexico	Hospital General de Culiacan	Culiacan
Mexico	Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran	Mexico
Peru	Hospital Militar Central	Jesus Maria
Peru	Hospital Maria Auxiliadora	Lima
Peru	Hospital Nacional Cayetano Heredia	Lima
Peru	Hospital Nacional Hipolito; Unanue	Lima
Peru	Hospital Nacional Sergio E. Bernales	Lima
South Africa	George Provincial Hospital	George
United States	St. Lukes Boise Medical Center	Boise	Idaho
United States	St. Barnabas Hospital	Bronx	New York
United States	SUNY Downstate Medical Center.	Brooklyn	New York
United States	Novant Health Presbyterian Medical Center (Presbyterian Hospital)	Charlotte	North Carolina
United States	Henry Ford Health System	Detroit	Michigan
United States	El Centro Regional Medical Center	El Centro	California
United States	Elmhurst Hospital Center	Elmhurst	New York
United States	San Juan Oncology Associates	Farmington	New Mexico
United States	Cape Fear Valley Medical Center	Fayetteville	North Carolina
United States	Flushing Hospital	Flushing	New York
United States	Holy Cross Germantown Hospital	Germantown	Maryland
United States	Valley Baptist Medical Center	Harlingen	Texas
United States	Larkin Community Hospital Palm Springs Campus (Hialeah)	Hialeah	Florida
United States	Michael E Debakey VA Medical Center	Houston	Texas
United States	Jamaica Hospital Medical Center	Jamaica	New York
United States	eStudySite	La Mesa	California
United States	McAllen Medical Center	McAllen	Texas
United States	Miami Veterans Administration Healthcare System - NAVREF	Miami	Florida
United States	University of Miami Pulmonary	Miami	Florida
United States	Ochsner Clinic	New Orleans	Louisiana
United States	Harlem Hospital	New York	New York
United States	Highland Hospital Oakland	Oakland	California
United States	St. Joseph'S Hospital	Orange	California
United States	St. Joseph'S Regional Medical Center	Paterson	New Jersey
United States	Temple University Hospital	Philadelphia	Pennsylvania
United States	Banner - University Medical Center Phoenix; In-Patient Pharmacy	Phoenix	Arizona
United States	Canton-Potsdam Hospital	Potsdam	New York
United States	San Leandro Hospital; Inpatient Pharmacy	San Leandro	California
United States	Holy Cross Hospital	Silver Spring	Maryland
United States	Larkin Community Hospital	South Miami	Florida
United States	Univ of AZ Coll of Med	Tucson	Arizona
United States	Sentara Medical Group	Virginia Beach	Virginia

Sponsors (1)

Lead Sponsor	Collaborator
Genentech, Inc.

Countries where clinical trial is conducted

United States,  Brazil,  Kenya,  Mexico,  Peru,  South Africa, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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 - 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
Secondary	Time to Clinical Failure, Defined as the Time to Death, Mechanical Ventilation, ICU Admission, or Withdrawal (Whichever Occurred First)		Up to Day 28
Secondary	Mortality Rate by Day 28		Up to Day 28
Secondary	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 - 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	Percentage of Participants With Adverse Events		Up to Day 60