Trial of Tocilizumab for Treatment of Severe COVID-19: ARCHITECTS (ARCHITECTS)

A Randomized, Controlled Clinical Trial of the Safety and Efficacy of Tocilizumab for the Treatment of Severe COVID-19

The overall objective is to evaluate the clinical efficacy and safety of tocilizumab relative to placebo among approximately 300 hospitalized adult patients who have severe COVID-19. The study will be a 2 arm double blinded comparison between tocilizumab 8 mg/kg and matching placebo IV. The dose may be repeated in 8-12 hours if clinical symptoms worsens, (e.g. increase in oxygen requirements). Participants will be followed for 28 days.

Study Overview

• Status: Unknown
• Conditions: COVID-19
• Intervention / Treatment: Drug: Tocilizumab; Drug: Placebo

• Study Type: Interventional
• Enrollment (Anticipated): 300
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Todd Seto, MD; Phone Number: 808 354-3533; Email: tseto@queens.org
• Study Contact Backup: Name: May Vawer, RN; Phone Number: 808 691-7185; Email: mvawer@queens.org

Study Locations

• United States
  • Hawaii
    • Honolulu, Hawaii, United States, 96813
      • Recruiting
      • Queen's Medical Center
      • Contact: May Vawer, RN; Phone Number: 808 691-7185; Email: mvawer@queens.org
      • Contact: Todd Seto, MD; Phone Number: 808-354-3533; Email: tseto@queens.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 95 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• ii. Hospitalized with COVID-19 pneumonia, based on chest X-ray or CT scan AND iii. Evidence of hyperinflammation: IL-6>40pg/mL (if available) OR CRP >2 mg/dL OR ferritin >2000 ng/mL AND iv. One or more of the following: impending need for requiring invasive or non-invasive mechanical ventilation OR shock requiring vasopressor (without evidence of bacterial / fungal infection) OR need for extracorporeal membrane oxygenation (ECMO) OR severe, refractor ARDS (PaO2/FiO2<200 mmHg)

Exclusion Criteria:

Known severe allergic reactions to tocilizumab or other monoclonal antibodies

• Active tuberculosis infection based on history
• 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 tocilizumab) with the past 6 months
• Participating in other drug clinical trials (participation in COVID-19 trials allowed)
• Self-reported pregnant or breastfeeding
• 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 baseline
• Absolute neutrophil count (ANC) < 1000/mL at baseline
• Platelet count < 50,000/mL at baseline

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / 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.	Drug: Tocilizumab; Participants will receive 1 dose of IV TCZ. 1 additional dose may be given if clinical symptoms worsen.; Other Names: Actemra
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.	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical status (on a 7-point ordinal scale) at day 28	Clinical Status 7-point ordinal scale: Not hospitalized, no limitations on activities; Not hospitalized, limitation on activities; Hospitalized, not requiring supplemental oxygen; Hospitalized, requiring supplemental oxygen; Hospitalized, on non-invasive ventilation or high flow oxygen devices; Hospitalized, on invasive mechanical ventilation or ECMO; Death	up to day 28

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical improvement	ii. Time to clinical improvement, defined as a National Early Warning Score (NEWS) of < 2 maintained for 24 hours iii. Time to clinical improvement of at least 2 categories relative to baseline on a 7-category ordinal scale of clinical status	up to day 28
Mechanical Ventilation	iv. Incidence of mechanical ventilation v. Ventilator-free days	up to day 28
Oxygenation	vi. Duration of time on supplemental oxygen	up to day 28

Collaborators and Investigators

• Sponsor: Queen's Medical Center

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 12, 2020
• Primary Completion (ANTICIPATED): December 31, 2021
• Study Completion (ANTICIPATED): December 31, 2021

Study Registration Dates

• First Submitted: June 1, 2020
• First Submitted That Met QC Criteria: June 1, 2020
• First Posted (ACTUAL): June 2, 2020

Study Record Updates

• Last Update Posted (ACTUAL): November 17, 2020
• Last Update Submitted That Met QC Criteria: November 13, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19
• Other Study ID Numbers: RA-2020-019

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes