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Completed

NCT Number: NCT04320615

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

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.

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Key information

Conditions

COVID-19 Pneumonia

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Hamilton General Hospital; Pharmacy, Hamilton, Ontario, Canada

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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)

Treatment and study plan

Tocilizumab (TCZ)

Drug

Participants will receive 1 dose of IV TCZ. 1 additional dose may be given if clinical symptoms worsen or show no improvement.

Placebo

Drug

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.

Primary outcomes

  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:

    • - Discharged (or "ready for discharge")
    • - 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

Secondary outcomes

  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:

    • - Discharged (or "ready for discharge")
    • - 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

  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.

Sponsors and collaborators

Lead sponsor

Hoffmann-La Roche

Industry

Registry information

Official study title

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

Acronym: COVACTA

Important dates

Study start
2020
Primary completion
2020
Study completion
2020
First posted
Mar 25, 2020
Registry last updated
Jun 30, 2021

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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