Tocilizumab for Acute Chest Syndrome

Low-Dose Tocilizumab for Acute Chest Syndrome in Sickle Cell Disease

The investigators are evaluating the role of a low dose of tocilizumab in treating acute chest syndrome in patients with sickle cell disease. Tocilizumab inhibits interleukin-6 (IL-6) receptors and is used to treat rheumatoid arthritis and severe cytokine release syndrome, which can be seen with chimeric antigen receptor T-cell (CAR-T) therapy, and it is also authorized for treatment of COVID-19. Since IL-6 levels are elevated in the sputum of patients with acute chest syndrome, the investigators are hopeful that this will be an effective strategy. The investigators will be looking at how a low dose of tocilizumab affects oxygen status, clinical outcomes, and laboratory markers in patients admitted to the hospital with acute chest syndrome.

Study Overview

• Status: Recruiting
• Conditions: Sickle Cell Disease; Acute Chest Syndrome
• Intervention / Treatment: Drug: Tocilizumab

Detailed Description

In this randomized, placebo-controlled, double-blinded phase II study, enrolled patients admitted to the University of Chicago who are diagnosed with acute chest syndrome will receive one dose of tocilizumab 80 mg IV and one normal saline placebo dose. The order of these doses will be randomized at a 1:1 ratio. After collecting oxygenation data as a baseline for 8 hours, patients will then receive tocilizumab versus placebo as their early dose and then the opposite (placebo versus tocilizumab) 48 hours later. Clinical, laboratory, and patient-reported outcome data will be collected during their admission and compared between arms.

• Study Type: Interventional
• Enrollment (Estimated): 200
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Austin Wesevich, MD; Phone Number: 773-834-6732; Email: austin.wesevich@uchicagomedicine.org
• Study Contact Backup: Name: Gabrielle Lapping-Carr, MD; Phone Number: 773-702-6808; Email: glappingcarr@uchicago.edu

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60637
      • Recruiting
      • University of Chicago
      • Contact: Austin Wesevich, MD; Phone Number: 773-834-6732; Email: austin.wesevich@uchicagomedicine.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adults ≥ 12 years of age
• Prior diagnosis of sickle cell disease (Hb SS, Hb SC, Hb Sb+, and Hb Sb0)

Exclusion Criteria:

• Pregnant patients or breastfeeding mothers.
• Prior treatment with gene therapy or a stem cell transplant.
• Current enrollment in a clinical trial involving an FDA-regulated drug or biologic.
• Current neutropenia (absolute neutrophil count < 1000/mm^3)
• Current thrombocytopenia (platelet count < 50,000 mm^3)
• Aspartate aminotransferase (AST) or alanine transaminase (ALT) > 10 times the upper limit of normal (ULN)
• History of tuberculosis (TB).
• Positive purified protein derivative (PPD) TB screening test.
• 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: Baricitinib, Ruxolitinib, Tofacitinib, Upadacitinib
• Any of the following biologic immunosuppressive agent (and any biosimilar versions thereof) administered in the past 6 months:

Abatacept, Adalimumab, Alemtuzumab, Atezolizumab, Belimumab, Blinatumomab, Brentuximab, Certolizumab, Daratumumab, Durvalumab, Eculizumab, Elotuzumab, Etanercept, Gemtuzumab, Golimumab, Ibritumomab, Infliximab, Inotuzumab, Ipilimumab, Ixekizumab, Moxetumomab, Nivolumab, Obinutuzumab, Ocrelizumab, Ofatumumab, Pembrolizumab, Polatuzumab, Rituximab, Sarilumab, Secukinumab, Tocilizumab, Tositumumab, Tremelimumab, Urelumab, Ustekinumab

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Early Tocilizumab; This arm will receive tocilizumab 80 mg at the time of acute chest syndrome diagnosis and subsequent randomization. Then, two days later, they will receive 50 mL of normal saline.	Drug: Tocilizumab; Tocilizumab 80 mg IV dose (one time per patient)
Active Comparator: Delayed Tocilizumab; This arm will receive 50 mL of normal saline at the time of acute chest syndrome diagnosis and subsequent randomization. Then, two days later, they will receive tocilizumab 80 mg. Thus, this delayed arm will serve as a placebo comparator for the first 48 hours and then as an active comparator for the remaining duration on study.	Drug: Tocilizumab; Tocilizumab 80 mg IV dose (one time per patient)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time-weighted SaO2/FiO2 ratio	Oxygenation data will be obtained as part of routine clinical care. All changes in pulse oximetry measurement that are documented in the chart will be recorded in an oxygen saturation case report form with the date and time from Day 0 to Day 4. These peripheral oxygen saturation (SpO2) measurements will serve as surrogates for SaO2. Additionally, all changes in the route of supplemental oxygen delivery, rate of supplemental oxygen delivery, and fraction of inspired oxygen (FiO2) will be recorded in a corresponding case report form with the date and time from Day 0 to Day 4. The time-weighted SaO2/FiO2 ratio, our primary endpoint, will be calculated based on these two case report forms.	Total of 4 days (Day 0 to Day 4)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Red cell exchange transfusion rate	As part of routine clinical care by the inpatient team, patients may receive a red cell exchange transfusion. The study team will assess if participants received any exchange transfusions from Day 0 to Day 8, and if so, they will record the date of the first exchange transfusion and the total number of units transfused during that time period.	Total of 9 days (Day 0 to Day 8)
Intensive Care Unit (ICU) transfer rate	Patients will be assessed for if they were admitted directly to the intensive care unit (ICU) or if they were transferred from the general medicine floor to the ICU between Day 0 and Day 8. The date of transfer to the ICU will be recorded if applicable.	Total of 9 days (Day 0 to Day 8)
Length of stay	Patients will be assessed for their admission and discharge dates. Length of stay will be calculated based on those two dates.	Up to 3 months (Admission Date to Discharge Date)
Readmission rate	Patients will be assessed for readmission for 28 days from discharge. Readmission will be assessed at the University of Chicago as well as through any linked hospitals through Care Everywhere within the electronic medical record system. The date of readmission will be recorded if applicable.	Total of 29 days (Discharge Date to 28 days after discharge)
Mortality rate	Patients will be assessed for mortality from Day 0 to Day 28. The date of death will be recorded if applicable.	Total of 29 days (Day 0 to Day 28)

Collaborators and Investigators

• Sponsor: University of Chicago
• Investigators: Principal Investigator: Austin Wesevich, MD, University of Chicago

Study record dates

Study Major Dates

• Study Start (Actual): April 10, 2023
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): January 1, 2027

Study Registration Dates

• First Submitted: November 28, 2022
• First Submitted That Met QC Criteria: November 28, 2022
• First Posted (Actual): December 7, 2022

Study Record Updates

• Last Update Posted (Actual): April 6, 2026
• Last Update Submitted That Met QC Criteria: March 31, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Respiratory Tract Diseases; Lung Diseases; Respiration Disorders; Hematologic Diseases; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hemoglobinopathies; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hemic and Lymphatic Diseases; Anemia, Sickle Cell; Acute Chest Syndrome; tocilizumab
• Other Study ID Numbers: IRB22-0277

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