Low-dose Tocilizumab Versus Standard of Care in Hospitalized Patients With COVID-19

NCT04479358 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: IRB20-1179
• Study Type: interventional
• Target: 85
• Locations: 1 country
• Sites: 1

Brief Summary

Tocilizumab is an effective treatment for severe coronavirus disease 2019 (Covid-19) pneumonia and related inflammation. Given limited global supplies, clarification of the optimal tocilizumab dose is critical. We conducted an open-label, randomized, controlled trial evaluating two different dose levels of tocilizumab in Covid-19 (40mg and 120mg). Randomization was stratified on remdesivir and corticosteroid at enrollment. The primary outcome was the time to recovery. The key secondary outcome was 28-day mortality.

Conditions

COVID-19

Keywords

COVID-19; Tocilizumab

Outcome Measures

Primary Outcomes (1)

• Time to Recovery

  Day of recovery is defined as the first day on which the patient achieves one of the following two categories from the seven-point ordinal scale: 6) Hospitalized, not requiring supplemental oxygen or ongoing medical care or 7) Not hospitalized. Time to recovery is the number of days from randomization to achievement of this status. Note that the ordinal scale is measured once daily, with the patient's worst clinical status during the 24-hour time period (0:00-23:59) being documented.

  28 days

Secondary Outcomes (13)

• Achievement of Recovery

  7 days

• Overall Survival

  28 days

• Hospital Length of Stay

  Up to 1 year

• Clinical Response: Maximum Temperature (Tmax) Response

  24 hours

• Clinical Response: Rate of Non-Elective Invasive Mechanical Ventilation

  Up to 28 days

Study Arms (6)

Sub-study A, Tocilizumab-Free Standard of Care

ACTIVE COMPARATOR

Patient assigned to Sub-study A by primary treating physicians. Patient enrolled on trial sub-study A and randomized to receive no tocilizumab.

Other: Standard of Care

Sub-study A, Tocilizumab 40mg

EXPERIMENTAL

Patient assigned to Sub-study A by primary treating physicians. Patient enrolled on trial sub-study A and randomized to receive tocilizumab 40mg.

Drug: Tocilizumab

Sub-study A, Tocilizumab 120mg

EXPERIMENTAL

Patient assigned to Sub-study A by primary treating physicians. Patient enrolled on trial sub-study A and randomized to receive tocilizumab 120mg.

Drug: Tocilizumab

Sub-study B, Tocilizumab 400mg or 8mg/kg Standard of Care

ACTIVE COMPARATOR

Patient assigned to Sub-study B by primary treating physicians. Patient enrolled on trial sub-study B and randomized to receive standard of care tocilizumab dose (400mg or 8mgkg).

Other: Standard of Care

Sub-study B, Tocilizumab 40mg

EXPERIMENTAL

Patient assigned to Sub-study B by primary treating physicians. Patient enrolled on trial sub-study B and randomized to receive standard of care tocilizumab 40mg.

Drug: Tocilizumab

Sub-study B, Tocilizumab 120mg

EXPERIMENTAL

Patient assigned to Sub-study B by primary treating physicians. Patient enrolled on trial sub-study B and randomized to receive standard of care tocilizumab 120mg.

Drug: Tocilizumab

Interventions

Tocilizumab DRUG

Tocilizumab 40mg

Also known as: Tocilizumab 40mg

Sub-study A, Tocilizumab 40mg; Sub-study B, Tocilizumab 40mg

Standard of Care OTHER

Tocilizumab-Free Standard of Care

Sub-study A, Tocilizumab-Free Standard of Care

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults ≥ 18 years of age
• Approval from the patient's primary inpatient service
• Hospitalized
• Fever, documented in electronic medical record and defined as: T ≥ 38 degrees C by any conventional clinical method (forehead, tympanic, oral, axillary, rectal)
• Positive test for active SARS-CoV-2 infection
• Radiographic evidence of infiltrates on chest radiograph (CXR) or computed tomography (CT)
• Ability to provide written informed consent on the part of the subject or, in the absence of decisional capacity of the subject, an appropriate surrogate (e.g. a legally authorized representative).

You may not qualify if:

• Concurrent use of invasive mechanical ventilation
• Concurrent use of vasopressor or inotropic medications
• Previous receipt of tocilizumab or another anti-IL6R or IL-6 inhibitor in the year prior.
• Known history of hypersensitivity to tocilizumab.
• Diagnosis of end-stage liver disease or listed for liver transplant.
• Elevation of AST or ALT in excess of 10 times the upper limit of normal.
• Neutropenia (Absolute neutrophil count \< 500/uL).
• Thrombocytopenia (Platelets \< 50,000/uL).
• On active therapy with a Bruton's tyrosine kinase-targeted agent, which include the following:
• Acalabrutinib
• Ibrutinib
• Zanubrutinib
• On active therapy with a JAK2-targeted agent, which include the following:
• Tofacitinib
• Baricitinib

Sponsors & Collaborators

• University of Chicago: lead

Study Sites (1)

University of Chicago Medicine

Chicago, Illinois, 60637, United States

Location

Related Publications (1)

• Strohbehn GW, Reid PD, Ratain MJ. Applied Clinical Pharmacology in a Crisis: Interleukin-6 Axis Blockade and COVID-19. Clin Pharmacol Ther. 2020 Sep;108(3):425-427. doi: 10.1002/cpt.1931. Epub 2020 Jul 4.

  PMID: 32488861 BACKGROUND

MeSH Terms

Conditions

COVID-19

Interventions

tocilizumab; Standard of Care

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Results Point of Contact

• Title: Pankti Reid, MD
• Organization: University of Chicago

pankti.reid@bsd.uchicago.edu

7737021220

Study Officials

• Pankti D Reid, MD, MPH

  University of Chicago

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Two sub-studies in parallel, each of three arms (maximum).

Study Record Dates

• First Submitted: July 13, 2020
• First Posted: July 21, 2020
• Study Start: September 10, 2020
• Primary Completion: March 1, 2024
• Study Completion: February 10, 2025
• Last Updated: March 30, 2026
• Results First Posted: June 5, 2025

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, ANALYTIC CODE
• Time Frame: From 1 month following publication of data. Available indefinitely thereafter.
• Access Criteria: Proposals will need to be sent to study principal investigators. Requestors will need to sign a data access request form. Link to be determined.

Locations

US (1)