Tocilizumab for Acute Chest Syndrome

NCT05640271 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: IRB22-0277
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Sickle Cell Disease; Acute Chest Syndrome

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• Red cell exchange transfusion rate

  Total of 9 days (Day 0 to Day 8)

• Intensive Care Unit (ICU) transfer rate

  Total of 9 days (Day 0 to Day 8)

• Length of stay

  Up to 3 months (Admission Date to Discharge Date)

• Readmission rate

  Total of 29 days (Discharge Date to 28 days after discharge)

• Mortality rate

  Total of 29 days (Day 0 to Day 28)

Study Arms (2)

Early Tocilizumab

EXPERIMENTAL

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

Delayed Tocilizumab

ACTIVE COMPARATOR

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

Interventions

Tocilizumab DRUG

Tocilizumab 80 mg IV dose (one time per patient)

Delayed Tocilizumab; Early Tocilizumab

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Chicago: lead

Study Sites (1)

University of Chicago

Chicago, Illinois, 60637, United States

RECRUITING

MeSH Terms

Conditions

Anemia, Sickle Cell; Acute Chest Syndrome

Interventions

tocilizumab

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Lung Diseases; Respiratory Tract Diseases; Respiration Disorders

Study Officials

• Austin Wesevich, MD

  University of Chicago

  STUDY DIRECTOR

Central Study Contacts

Austin Wesevich, MD

CONTACT

773-834-6732; austin.wesevich@uchicagomedicine.org

Gabrielle Lapping-Carr, MD

CONTACT

773-702-6808; glappingcarr@uchicago.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The study statistician will generate randomizations using the method of permuted block randomization. The pharmacy will access the prepared randomization list via REDCap (a module separate from the clinical REDCap database) to guide tocilizumab versus placebo administration at the time of placing an inpatient order. Prior to randomization, the SpO2 to FiO2 ratio will be determined over an 8-hour period to serve as a baseline measure. Thus, randomization will be done at the time of placing the initial order for inpatient tocilizumab versus placebo, not at the time of enrollment. Patients, study investigators, and inpatient clinicians will all be blinded to the patient's randomized group assignment. Only the investigational pharmacy will be aware of the randomization arm.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: All participants will receive tocilizumab 80 mg on one day and placebo (normal saline 50 mL) on another day, separated by 48 hours, and the order of these two doses will be randomized. Half the patients will receive tocilizumab at the time of acute chest syndrome diagnosis and subsequent randomization, and then that half will receive placebo two days later. The other half will receive placebo first and then tocilizumab two days later.

Study Record Dates

• First Submitted: November 28, 2022
• First Posted: December 7, 2022
• Study Start: April 10, 2023
• Primary Completion: April 1, 2026
• Study Completion (Estimated): January 1, 2027
• Last Updated: April 2, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)