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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04320615
Recruitment Status : Completed
First Posted : March 25, 2020
Results First Posted : June 30, 2021
Last Update Posted : June 30, 2021
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Study Description
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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.

Condition or disease Intervention/treatment Phase
COVID-19 Pneumonia Drug: Tocilizumab (TCZ) Drug: Placebo Phase 3

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 452 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Safety and Efficacy of Tocilizumab in Patients With Severe COVID-19 Pneumonia
Actual Study Start Date : April 3, 2020
Actual Primary Completion Date : June 24, 2020
Actual Study Completion Date : July 28, 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Tocilizumab

Arms and Interventions
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Arm Intervention/treatment
Experimental: Tocilizumab (TCZ) Arm
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)
Participants will receive 1 dose of IV TCZ. 1 additional dose may be given if clinical symptoms worsen or show no improvement.
Placebo Comparator: Placebo Arm
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
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.


Outcome Measures
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Primary Outcome Measures :
  1. Clinical Status Assessed Using a 7-Category Ordinal Scale at Day 28 (Week 4) [ Time Frame: Day 28 ]

    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


Secondary Outcome Measures :
  1. Time to Clinical Improvement (TTCI), Defined as a National Early Warning Score 2 (NEWS2) of </= 2 Maintained for 24 Hours [ Time Frame: Up to Day 28 ]
    Defined as time from first dose of study drug to at least two NEWS2 assessments with a score of <=2 covering a span of at least 21.5 hours, with a maximum of 26.5 hours between the first and last of these assessments and no assessments with a score >2 in between. If one of the components of the NEWS2 score was missing at a particular time point, then the NEWS2 score was not calculated. Participants who died were censored at Day 28.

  2. Time to Improvement of at Least 2 Categories Relative to Baseline on a 7-Category Ordinal Scale of Clinical Status [ Time Frame: Up to Day 28 ]
    Time to improvement for this outcome measure was defined as the days from the first dose of study drug to when at least a 2-category improvement in clinical status (based on a 7-category ordinal scale) is observed. Participants who died were censored at Day 28.

  3. Time to Hospital Discharge or "Ready for Discharge" [ Time Frame: Up to Day 28 ]
    Time to Hospital Discharge was defined as the time from the first dose of study drug to hospital discharge or "ready for discharge" (normal body temperature and respiratory rate, and stable oxygen saturation on ambient air or </=2L supplemental oxygen) Participants who died were censored at Day 28.

  4. Incidence of Mechanical Ventilation by Day 28 [ Time Frame: Up to Day 28 ]
    Participants who died by Day 28 were assumed to have required mechanical ventilation.

  5. Ventilator-Free Days to Day 28 [ Time Frame: Up to Day 28 ]
    Participants who died by Day 28 were assigned 0 ventilator-free days.

  6. Incidence of Intensive Care Unit (ICU) Stay by Day 28 (Week 4) [ Time Frame: Up to Day 28 ]
    Participants who died by Day 28 were assumed to have required an ICU stay.

  7. Duration of ICU Stay to Day 28 (Week 4) [ Time Frame: Up to Day 28 ]
    Participants who died by Day 28 were assigned a duration from the first dose of study drug to Day 28 at hour 23:59:59.

  8. Clinical Status Assessed Using a 7-Category Ordinal Scale at Day 14 [ Time Frame: Day 14 ]

    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

  9. Time to Clinical Failure to Day 28 (Week 4) [ Time Frame: Up to Day 28 ]
    Time to clinical failure was defined as the number of days from the first dose of study drug to the first occurrence on study of death, mechanical ventilation, ICU admission, or study withdrawal prior to discharge, whichever occurs first.

  10. Mortality Rate at Day 28 (Week 4) [ Time Frame: Day 28 ]
  11. Time to Recovery to Day 28 (Week 4) [ Time Frame: Up to Day 28 ]
    Time to recovery was defined as the number of days from the first dose of study drug to hospital discharge or "ready for discharge" (normal body temperature and respiratory rate, and stable oxygen saturation on ambient air or </= 2L supplemental oxygen) or non-ICU hospital ward or "ready for hospital ward" not requiring supplemental oxygen. Participants who died were censored at Day 28.

  12. Duration of Supplemental Oxygen to Day 28 (Week 4) [ Time Frame: Up to Day 28 ]
    Participants who died by Day 28 were assigned a duration of 28 days of supplemental oxygen.


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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)
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04320615


Locations
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Sponsors and Collaborators
Hoffmann-La Roche
Investigators
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Study Director: Clinical Trials Hoffmann-La Roche
  Study Documents (Full-Text)

Documents provided by Hoffmann-La Roche:
Study Protocol  [PDF] June 11, 2020
Statistical Analysis Plan  [PDF] July 16, 2020

More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT04320615    
Other Study ID Numbers: WA42380
2020-001154-22 ( EudraCT Number )
First Posted: March 25, 2020    Key Record Dates
Results First Posted: June 30, 2021
Last Update Posted: June 30, 2021
Last Verified: June 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description:

Qualified researchers may request access to individual patient level data through the clinical study data request platform https://vivli.org.

Further details on Roche's criteria for eligible studies are available here: https://vivli.org.

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

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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COVID-19
Pneumonia
Pneumonia, Viral
Respiratory Tract Infections
Infections
Virus Diseases
 Coronavirus Infections
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Lung Diseases
Respiratory Tract Diseases