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

Queen's Medical Center

Status and phase: Unknown; Phase 3

Conditions: COVID-19

Treatments: Drug: Tocilizumab; Drug: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT04412772

RA-2020-019

Details and patient eligibility

About

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.

Enrollment: 300 estimated patients

Sex: All

Ages: 18 to 95 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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300 participants in 2 patient groups, including a placebo group

Tocilizumab (TCZ) Arm

Experimental group

Description:

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.

Treatment:

Drug: Tocilizumab

Placebo Arm

Placebo Comparator group

Description:

Participants will receive 1 IV infusion of placebo matched to TCZ. Up to 1 additional dose may be given if clinical symptoms worsen.

Treatment:

Drug: Placebo