Tocilizumab to Prevent Clinical Decompensation in Hospitalized, Non-critically Ill Patients With COVID-19 Pneumonitis

NCT04331795 | Completed Phase 2 Results FDA Drug

• 1 other identifier: IRB20-0515
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

Coronavirus disease-2019 (COVID-19) has a quoted inpatient mortality as high as 25%. This high mortality may be driven by hyperinflammation resembling cytokine release syndrome (CRS), offering the hope that therapies targeting the interleukin-6 (IL-6) axis therapies commonly used to treat CRS can be used to reduce COVID-19 mortality. Retrospective analysis of severe to critical COVID-19 patients receiving tocilizumab demonstrated that the majority of patients had rapid resolution (i.e., within 24-72 hours following administration) of both clinical and biochemical signs (fever and CRP, respectively) of hyperinflammation with only a single tocilizumab dose. Hypotheses:

1. 1.Tocilizumab is effective in decreasing signs, symptoms, and laboratory evidence of COVID-19 pneumonitis in hospitalized, non-critically ill patients with clinical risk factors for clinical decompensation, intensive care utilization, and death.
2. 2.Low-dose tocilizumab is effective in decreasing signs, symptoms, and laboratory evidence of COVID-19 pneumonitis in hospitalized, non-critically ill patients with and without clinical risk factors for clinical decompensation, intensive care utilization, and death.
3. 3.To establish proof of concept that tocilizumab is effective in decreasing signs, symptoms, and laboratory evidence of COVID-19 pneumonitis in hospitalized, non-critically ill patients with clinical risk factors for clinical decompensation, intensive care utilization, and death, as determined by the clinical outcome of resolution of fever and the biochemical outcome measures of time to CRP normalization for the individual patient and the rate of patients whose CRP normalize.
4. 4.To establish proof of concept that low-dose tocilizumab is effective in decreasing signs, symptoms, and laboratory evidence of COVID-19 pneumonitis in hospitalized, non-critically ill patients without clinical risk factors for clinical decompensation, intensive care utilization, and death, as determined by the clinical outcome of resolution of fever and the biochemical outcome measures of time to CRP normalization for the individual patient and the rate of patients whose CRP normalize.

Conditions

COVID-19

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Clinical Response in Maximum Temperature (Tmax)

  Number of Participants with Clinical Response in Maximum Temperature (Tmax)

  Assessed for the 24 hour period after tocilizumab administration

• Number of Participants With Biochemical Response as Determined by CRP Response

  Number of Participants with Biochemical Response as determined by CRP Response. Defined as at least 25% decrease in CRP from baseline at least 16 hours after administration of drug.

  Assessed every 24 hours during patient's hospitalization, up to 4 weeks after tocilizumab administration

Secondary Outcomes (11)

• Overall Survival

  28 days

• Survival to Hospital Discharge

  Hospitalization, up to 4 weeks after tocilizumab administration

• Progression of COVID-19 Pneumonitis

  Hospitalization, up to 4 weeks after tocilizumab administration

• Rate of Non-elective Mechanical Ventilation

  Hospitalization, up to 4 weeks after tocilizumab administration

• Duration of Mechanical Ventilation

  Hospitalization, up to 4 weeks after tocilizumab administration

Study Arms (2)

Group A

EXPERIMENTAL

Hospitalized, non-critically ill patients with COVID-19 pneumonitis with risk factors for decompensation

Drug: Tocilizumab

Group B

EXPERIMENTAL

Hospitalized, non-critically ill patients with COVID-19 pneumonitis without risk factors for decompensation

Drug: Tocilizumab

Interventions

Tocilizumab DRUG

Group A: Tocilizumab (beginning dose 200mg) Single dose is provisioned, patient is eligible to receive up to two doses, with re-evaluation of clinical and biochemical responses performed every 24 hours. Second dose is provisioned if: 1. Increasing supplemental oxygen requirement or Tmax higher than baseline in the 24h following initial tocilizumab administration AND 2. CRP decrease is \< 25% at 24 hours following tocilizumab administration and CRP \> 40mg/L

Group A

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 service
• Admitted as an inpatient to University of Chicago Medicine
• Fever, documented in electronic medical record and defined as: T ≥ 38\*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 (patients receiving non-invasive mechanical ventilation \[CPAP, BiPap, HHFNC\] are eligible)
• Concurrent use of vasopressor or inotropic medications
• Previous receipt of tocilizumab or another anti-IL6R or IL-6 inhibitor.
• Known history of hypersensitivity to tocilizumab.
• Patients who are actively being considered for a study of an antiviral agent that would potentially exclude concurrent enrollment on this study.
• Patients actively receiving an investigational antiviral agent in the context of a clinical research study.
• Diagnosis of end-stage liver disease or listed for liver transplant.
• Elevation of AST or ALT in excess of 5 times the upper limit of normal.
• Neutropenia (Absolute neutrophil count \< 500/uL).
• Thrombocytopenia (Platelets \< 50,000/uL).
• On active therapy with a biologic immunosuppressive agent, which include the following biologics and any biosimilar versions thereof:
• Alemtuzumab
• Blinatumomab
• Brentuximab
• Daratumumab

Sponsors & Collaborators

• University of Chicago: lead

Study Sites (1)

University of Chicago Medicine

Chicago, Illinois, 60637, United States

Location

Related Publications (1)

• Strohbehn GW, Heiss BL, Rouhani SJ, Trujillo JA, Yu J, Kacew AJ, Higgs EF, Bloodworth JC, Cabanov A, Wright RC, Koziol AK, Weiss A, Danahey K, Karrison TG, Edens CC, Bauer Ventura I, Pettit NN, Patel BK, Pisano J, Strek ME, Gajewski TF, Ratain MJ, Reid PD. COVIDOSE: A Phase II Clinical Trial of Low-Dose Tocilizumab in the Treatment of Noncritical COVID-19 Pneumonia. Clin Pharmacol Ther. 2021 Mar;109(3):688-696. doi: 10.1002/cpt.2117. Epub 2020 Dec 10.

  PMID: 33210302 RESULT

MeSH Terms

Conditions

COVID-19

Interventions

tocilizumab

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

Results Point of Contact

• Title: Dr. Pankti Reid
• Organization: University of Chicago, Department of Medicine Section of Rheumatology

pankti.reid@uchospitals.edu

773-702-6119

Study Officials

• Pankti Reid, MD, MPH

  University of Chicago, Department of Medicine, Section of Rheumatology

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Study Record Dates

• First Submitted: April 1, 2020
• First Posted: April 2, 2020
• Study Start: April 4, 2020
• Primary Completion: June 5, 2020
• Study Completion: June 5, 2020
• Last Updated: June 9, 2022
• Results First Posted: June 9, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)