Clinical trial NCT05640271: Tocilizumab for Acute Chest Syndrome
Official title: Low-Dose Tocilizumab for Acute Chest Syndrome in Sickle Cell Disease
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Sickle Cell Disease
Acute Chest Syndrome
Lead sponsor: University of Chicago
Sponsor class: OTHER
First posted: 2022-12-07
Enrollment: 200
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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.
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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 \&amp;lt; 1000/mm\^3)
* Current thrombocytopenia (platelet count \&amp;lt; 50,000 mm\^3)
* Aspartate aminotransferase (AST) or alanine transaminase (ALT) \&amp;gt; 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

Primary outcomes:
measure: Time-weighted SaO2/FiO2 ratio
timeFrame: Total of 4 days (Day 0 to Day 4)
Secondary outcomes:
measure: Red cell exchange transfusion rate
timeFrame: Total of 9 days (Day 0 to Day 8)
measure: Intensive Care Unit (ICU) transfer rate
timeFrame: Total of 9 days (Day 0 to Day 8)
measure: Length of stay
timeFrame: Up to 3 months (Admission Date to Discharge Date)
measure: Readmission rate
timeFrame: Total of 29 days (Discharge Date to 28 days after discharge)
measure: Mortality rate
timeFrame: Total of 29 days (Day 0 to Day 28)
Other outcomes:
Locations:
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
Study officials:
affiliation: University of Chicago
name: Austin Wesevich, MD
role: STUDY_DIRECTOR
References: