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

Study Overview
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Brief Summary
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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.

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

Conditions
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COVID-19 Pneumonia

Intervention / Treatment
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* Drug: Placebo
* Drug: Tocilizumab


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Participants will receive one intravenous (IV) infusion of placebo, in addition to SOC. Up to one additional infusion may be given. | Drug: Placebo<br>* Participants will receive one dose of IV placebo matched to TCZ. Up to one additional dose may be given.<br>|
| Experimental: Tocilizumab<br>Participants will receive one IV infusion of TCZ in addition to SOC. Up to one additional infusion may be given. | Drug: Tocilizumab<br>* 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.<br>|

What is the study measuring?
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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 |