Tocilizumab for Acute Chest Syndrome

The University of Chicago

Status and phase: Enrolling; Phase 2

Conditions: Sickle Cell Disease; Acute Chest Syndrome

Treatments: Drug: Tocilizumab

Study type: Interventional

Funder types: Other

Identifiers

NCT05640271

IRB22-0277

Details and patient eligibility

About

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.

Full 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.

Enrollment: 200 estimated patients

Sex: All

Ages: 12+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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200 participants in 2 patient groups

Early Tocilizumab

Experimental group

Description:

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.

Treatment:

Drug: Tocilizumab

Delayed Tocilizumab

Active Comparator group

Description:

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.

Treatment:

Drug: Tocilizumab