Clinical trial NCT04372186: A Study to Evaluate the Efficacy and Safety of Tocilizumab in Hospitalized Participants With COVID-19 Pneumonia
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: COVID-19 Pneumonia
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
First posted: 2020-05-01
Enrollment: 377
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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

Primary outcomes:
measure: Cumulative Proportion of Participants Who Died or Required Mechanical Ventilation by Day 28
timeFrame: Up to Day 28
Secondary outcomes:
measure: 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)
timeFrame: Up to Day 28
measure: Time to Improvement of at Least 2 Categories Relative to Baseline on a 7-Category Ordinal Scale of Clinical Status
timeFrame: Up to Day 28
measure: Time to Clinical Failure, Defined as the Time to Death, Mechanical Ventilation, ICU Admission, or Withdrawal (Whichever Occurred First)
timeFrame: Up to Day 28
measure: Mortality Rate by Day 28
timeFrame: Up to Day 28
measure: Clinical Status on 7-Category Ordinal Scale at Day 28
timeFrame: Day 28
measure: Percentage of Participants With Adverse Events
timeFrame: Up to Day 60
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Banner - University Medical Center Phoenix; In-Patient Pharmacy
state: Arizona
city: Tucson
country: United States
facility: Univ of AZ Coll of Med
state: Arizona
city: El Centro
country: United States
facility: El Centro Regional Medical Center
state: California
city: La Mesa
country: United States
facility: eStudySite
state: California
city: Oakland
country: United States
facility: Highland Hospital Oakland
state: California
city: Orange
country: United States
facility: St. Joseph'S Hospital
state: California
city: San Leandro
country: United States
facility: San Leandro Hospital; Inpatient Pharmacy
state: California
city: Hialeah
country: United States
facility: Larkin Community Hospital Palm Springs Campus (Hialeah)
state: Florida
city: Miami
country: United States
facility: Miami Veterans Administration Healthcare System - NAVREF
state: Florida
city: Miami
country: United States
facility: University of Miami Pulmonary
state: Florida
city: South Miami
country: United States
facility: Larkin Community Hospital
state: Florida
city: Boise
country: United States
facility: St. Lukes Boise Medical Center
state: Idaho
city: New Orleans
country: United States
facility: Ochsner Clinic
state: Louisiana
city: Germantown
country: United States
facility: Holy Cross Germantown Hospital
state: Maryland
city: Silver Spring
country: United States
facility: Holy Cross Hospital
state: Maryland
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Paterson
country: United States
facility: St. Joseph'S Regional Medical Center
state: New Jersey
city: Farmington
country: United States
facility: San Juan Oncology Associates
state: New Mexico
city: Bronx
country: United States
facility: St. Barnabas Hospital
state: New York
city: Brooklyn
country: United States
facility: SUNY Downstate Medical Center.
state: New York
city: Elmhurst
country: United States
facility: Elmhurst Hospital Center
state: New York
city: Flushing
country: United States
facility: Flushing Hospital
state: New York
city: Jamaica
country: United States
facility: Jamaica Hospital Medical Center
state: New York
city: New York
country: United States
facility: Harlem Hospital
state: New York
city: Potsdam
country: United States
facility: Canton-Potsdam Hospital
state: New York
city: Charlotte
country: United States
facility: Novant Health Presbyterian Medical Center (Presbyterian Hospital)
state: North Carolina
city: Fayetteville
country: United States
facility: Cape Fear Valley Medical Center
state: North Carolina
city: Philadelphia
country: United States
facility: Temple University Hospital
state: Pennsylvania
city: Harlingen
country: United States
facility: Valley Baptist Medical Center
state: Texas
city: Houston
country: United States
facility: Michael E Debakey VA Medical Center
state: Texas
city: McAllen
country: United States
facility: McAllen Medical Center
state: Texas
city: Virginia Beach
country: United States
facility: Sentara Medical Group
state: Virginia
city: Campinas
country: Brazil
facility: Hospital E Maternidade Celso Pierro PUCCAMP
state: SP
city: Sao Bernardo Do Campo
country: Brazil
facility: Centro Multidisciplinar de Estudos Clínicos CEMEC FMABC
state: SP
city: Sao Paulo
country: Brazil
facility: BR Trials - Pesquisa Clínica
state: SP
city: Nairobi
country: Kenya
facility: Aga Khan University Hospital
city: Culiacan
country: Mexico
facility: Hospital General de Culiacan
city: Mexico
country: Mexico
facility: Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
city: Jesus Maria
country: Peru
facility: Hospital Militar Central
city: Lima
country: Peru
facility: Hospital Nacional Sergio E. Bernales
city: Lima
country: Peru
facility: Hospital Nacional Cayetano Heredia
city: Lima
country: Peru
facility: Hospital Nacional Hipolito; Unanue
city: Lima
country: Peru
facility: Hospital Maria Auxiliadora
city: George
country: South Africa
facility: George Provincial Hospital
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.