Tocilizumab for Acute Chest Syndrome

Overseen By Gabrielle Lapping-Carr, MD

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Chicago

Must not be taking: Bruton's inhibitors, JAK2 inhibitors, Biologics

Disqualifiers: Pregnancy, Gene therapy, Neutropenia, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 4 days

200 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop all current medications, but you cannot be on certain medications like Bruton's tyrosine kinase-targeted agents, JAK2-targeted agents, or certain biologic immunosuppressive agents. If you're taking any of these, you may need to stop them to participate.

What data supports the effectiveness of the drug Tocilizumab for treating acute chest syndrome?

Tocilizumab has been shown to be effective in treating various inflammatory conditions like rheumatoid arthritis and juvenile idiopathic arthritis by blocking a protein called interleukin-6 (IL-6) that causes inflammation. While it hasn't been specifically studied for acute chest syndrome, its success in reducing inflammation in other diseases suggests it might help in similar conditions. ^{1 2 3 4 5}

Is tocilizumab generally safe for humans?

Tocilizumab, also known as Actemra or RoActemra, has been used to treat various conditions like rheumatoid arthritis and juvenile idiopathic arthritis. It is generally well tolerated, but common side effects include infections such as upper respiratory tract infections. Serious infections can occur, and some patients may experience changes in blood tests, like low white blood cell counts or elevated liver enzymes. ^{1 2 4 6 7}

How does the drug tocilizumab differ from other treatments for acute chest syndrome?

Tocilizumab is unique because it targets the interleukin-6 receptor, which plays a role in inflammation, and is used in conditions like rheumatoid arthritis and cytokine release syndrome. This mechanism may offer a novel approach for treating acute chest syndrome, especially if inflammation is a key factor in the condition. ^{1 2 4 8 9}

Research Team

Austin Wesevich, MD

Principal Investigator

University of Chicago

Eligibility Criteria

This trial is for adults over 18 with sickle cell disease (various types). It's not for those who are pregnant, breastfeeding, or on certain immune-targeting drugs like Bruton's tyrosine kinase inhibitors or JAK2 agents. Also excluded are patients who've had specific biologic immunosuppressants in the last 6 months.

Inclusion Criteria

I have been diagnosed with sickle cell disease.

I am 18 years old or older.

Exclusion Criteria

I have not taken any immune-suppressing drugs in the last 6 months.

I am currently taking a medication that targets JAK2.

I am currently being treated with a specific cancer medication targeting Bruton's tyrosine kinase.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive tocilizumab 80 mg IV and a normal saline placebo dose, with the order randomized at a 1:1 ratio

4 days

Inpatient hospital stay

Follow-up

Participants are monitored for safety and effectiveness after treatment, including oxygenation data and clinical outcomes

4 weeks

Extended Follow-up

Participants are assessed for readmission and mortality for 28 days post-discharge

4 weeks

Treatment Details

Interventions

• Tocilizumab

Trial Overview Researchers are testing a low dose of Tocilizumab to treat acute chest syndrome in sickle cell patients. They want to see if it improves oxygen levels, clinical outcomes, and lab markers since IL-6 is high in these patients' sputum.

Participant Groups

Group I: Early Tocilizumab Experimental Treatment 1 Intervention

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.

Group II: Delayed Tocilizumab Active Control 1 Intervention

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.

Tocilizumab is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Actemra for:

• Rheumatoid Arthritis
• Systemic Juvenile Idiopathic Arthritis
• Polyarticular Juvenile Idiopathic Arthritis
• Giant Cell Arteritis
• Cytokine Release Syndrome
• COVID-19

Approved in United States as Actemra for:

• Rheumatoid Arthritis
• Systemic Juvenile Idiopathic Arthritis
• Polyarticular Juvenile Idiopathic Arthritis
• Giant Cell Arteritis
• Cytokine Release Syndrome
• COVID-19

Approved in Canada as Actemra for:

• Rheumatoid Arthritis
• Systemic Juvenile Idiopathic Arthritis
• Polyarticular Juvenile Idiopathic Arthritis
• Giant Cell Arteritis
• Cytokine Release Syndrome
• COVID-19

Approved in Japan as Actemra for:

• Rheumatoid Arthritis
• Systemic Juvenile Idiopathic Arthritis
• Polyarticular Juvenile Idiopathic Arthritis
• Giant Cell Arteritis
• Cytokine Release Syndrome
• COVID-19

Who Is Running the Clinical Trial?

University of Chicago

Lead Sponsor

Trials

1,086

Recruited

844,000+

Findings from Research

Tocilizumab is a humanized monoclonal antibody that targets the interleukin-6 receptor, showing efficacy in treating conditions like Castleman disease and various types of arthritis, with approval in Japan and the European Union for these uses.

The drug is currently under review by the US FDA for moderate-to-severe rheumatoid arthritis and has potential applications for other IL-6 related disorders, such as Crohn's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tocilizumab. Venkiteshwaran, A.[2021]

Tocilizumab is an effective treatment for systemic and polyarticular juvenile idiopathic arthritis (JIA) in children aged 2 years and older, showing significant improvement in patient responses compared to placebo in two phase III trials involving patients aged 2-17 years.

The drug was generally well tolerated, with infections being the most common adverse events; however, there was an approximately 11% annual risk of serious infections, indicating the need for monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tocilizumab: a review of its use in the treatment of juvenile idiopathic arthritis. Frampton, JE.[2021]

Tocilizumab, a monoclonal antibody targeting the IL-6 receptor, was effective in treating a 22-year-old woman with refractory systemic lupus erythematosus after she did not respond to multiple other therapies.

The patient experienced significant improvement in her symptoms, including fever, arthritis, and skin manifestations, allowing her to successfully taper off corticosteroids, highlighting the potential of tocilizumab in managing autoimmune diseases where IL-6 is involved.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful use of interleukin 6 antagonist tocilizumab in a patient with refractory cutaneous lupus and urticarial vasculitis. Makol, A., Gibson, LE., Michet, CJ.[2016]

Tocilizumab is an effective treatment for adults with moderate to severe rheumatoid arthritis (RA), showing beneficial effects on disease symptoms and quality of life, based on several large clinical trials and studies.

Long-term use of tocilizumab (up to 9 years) is generally well tolerated, with infections being the most common side effect, and it has been shown to be more effective than adalimumab in patients who cannot continue methotrexate.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravenous tocilizumab: a review of its use in adults with rheumatoid arthritis. Dhillon, S.[2022]

Tocilizumab (TCZ) effectively inhibits the IL-6 signaling pathway in rheumatoid arthritis (RA) patients, but it can mask typical signs of infections, as demonstrated in an 80-year-old woman who developed bacterial dermo-hypodermitis without fever or inflammatory symptoms after her 13th TCZ infusion.

Despite the absence of typical infection signs, the patient responded well to antibiotic treatment, highlighting the need for increased vigilance for atypical infections in RA patients receiving TCZ, as their inflammatory responses may be diminished.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Erysipelas without fever or biologic inflammation during tocilizumab therapy]. Yéléhé-Okouma, M., Henry, J., Petitpain, N., et al.[2018]

Tocilizumab, when used in combination with methotrexate (MTX) for treating rheumatoid arthritis (RA), is associated with a statistically significant increased risk of adverse events (AEs), particularly at the 8 mg/kg dosage, with an odds ratio of 1.53 compared to controls.

While there is a higher risk of infections in patients receiving the 8 mg/kg combination therapy (odds ratio of 1.30), the study found no increased incidence of malignancy, tuberculosis reactivation, or hepatitis, indicating a specific safety profile that requires monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk of adverse events including serious infections in rheumatoid arthritis patients treated with tocilizumab: a systematic literature review and meta-analysis of randomized controlled trials. Campbell, L., Chen, C., Bhagat, SS., et al.[2022]

Tocilizumab (Actemra) was granted emergency use authorization for treating COVID-19 in June 2021, but it has been associated with various skin-related side effects.

This study highlights both similarities and key differences between the skin reactions caused by tocilizumab and the common skin manifestations of COVID-19, which can help dermatologists make accurate diagnoses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tocilizumab Treatment in COVID-19 Patients: Comparing Cutaneous Disease and Adverse Drug Effects. Rosenberg, A., Waller, JD., Szeto, MD., et al.[2023]

Tocilizumab is a new biological treatment for adults with rheumatoid arthritis that specifically targets interleukin-6 (IL-6), a key pro-inflammatory cytokine involved in the disease.

The review evaluates the potential advantages of tocilizumab compared to other biological agents, suggesting it may offer unique benefits in managing rheumatoid arthritis symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tocilizumab for rheumatoid arthritis. [2017]

Tocilizumab, an anti-IL-6 receptor antibody, is effective in treating chronic autoimmune diseases like rheumatoid arthritis and has shown promise in alleviating cytokine storms from CAR-T-cell therapy.

Given its ability to target IL-6 overproduction, tocilizumab may also be a beneficial treatment for severe cases of COVID-19, which often involve cytokine release syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

IL-6: from arthritis to CAR-T-cell therapy and COVID-19. Kishimoto, T.[2021]

References

1. United States pubmed.ncbi.nlm.nih.gov

Tocilizumab. [2021]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Tocilizumab: a review of its use in the treatment of juvenile idiopathic arthritis. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Successful use of interleukin 6 antagonist tocilizumab in a patient with refractory cutaneous lupus and urticarial vasculitis. [2016]

4. New Zealand pubmed.ncbi.nlm.nih.gov

Intravenous tocilizumab: a review of its use in adults with rheumatoid arthritis. [2022]

5. France pubmed.ncbi.nlm.nih.gov

[Erysipelas without fever or biologic inflammation during tocilizumab therapy]. [2018]

6. England pubmed.ncbi.nlm.nih.gov

Risk of adverse events including serious infections in rheumatoid arthritis patients treated with tocilizumab: a systematic literature review and meta-analysis of randomized controlled trials. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Tocilizumab Treatment in COVID-19 Patients: Comparing Cutaneous Disease and Adverse Drug Effects. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Tocilizumab for rheumatoid arthritis. [2017]

9. England pubmed.ncbi.nlm.nih.gov

IL-6: from arthritis to CAR-T-cell therapy and COVID-19. [2021]