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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether a low dose of the drug tocilizumab can treat acute chest syndrome, a serious lung condition, in people with sickle cell disease. Tocilizumab blocks certain proteins in the body that cause inflammation. The trial compares two groups: one receives tocilizumab immediately, and the other receives it after two days. Participants must be over 12 years old and diagnosed with sickle cell disease. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group.

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.

Is there any evidence suggesting that tocilizumab is likely to be safe for humans?

Research shows that tocilizumab is generally safe for people. Studies have found that patients with severe COVID-19 and virus-related lung issues had good results when treated with tocilizumab. Already approved for rheumatoid arthritis and severe immune reactions, this drug's approval indicates its safety.

While this trial tests tocilizumab for a new use, its approval for other conditions supports its safety. Side effects can occur with any treatment, so discussing these with the trial team is important. However, existing research reassures about the safety of tocilizumab, especially given its successful use in other treatments. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for acute chest syndrome?

Most treatments for acute chest syndrome, like oxygen therapy, blood transfusions, and antibiotics, focus on managing symptoms and complications. But tocilizumab works differently by targeting and blocking the interleukin-6 (IL-6) receptor, which is involved in inflammation. This unique mechanism has the potential to reduce inflammation more effectively and quickly than current options. Researchers are excited because tocilizumab could offer a faster-acting solution, potentially improving outcomes for patients experiencing this serious condition.

What evidence suggests that tocilizumab might be an effective treatment for acute chest syndrome?

Research has shown that tocilizumab, a drug that blocks certain proteins, may help treat acute chest syndrome in people with sickle cell disease. These proteins, called IL-6, can cause inflammation, and their levels are often high in those with acute chest syndrome. Studies have found that tocilizumab works well for other inflammatory conditions, like rheumatoid arthritis and severe COVID-19 symptoms. In one case, a patient with acute chest syndrome related to COVID-19 showed significant improvement after taking tocilizumab. This trial will compare two approaches: the Early Tocilizumab arm, where participants receive tocilizumab at the time of diagnosis, and the Delayed Tocilizumab arm, where participants receive tocilizumab two days after diagnosis. This evidence suggests that tocilizumab could help reduce inflammation and improve health outcomes for patients with acute chest syndrome. ^{1 2 3 5 6}

Who Is on the Research Team?

Austin Wesevich, MD

Principal Investigator

University of Chicago

Are You a Good Fit for This Trial?

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.

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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, 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, 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, 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]

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 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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06818266

NCT06818266 | Efficacy and Safety of Tocilizumab for ... The purpose of this study is to determine whether a single infusion of tocilizumab is effective in reducing the time to successful weaning from both ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05640271

NCT05640271 | Tocilizumab for Acute Chest Syndrome Clinical, laboratory, and patient-reported outcome data will be collected during their admission and compared between arms. Official Title. Low-Dose Tocilizumab ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7267654/

Dramatic improvement after tocilizumab of severe COVID‐19 ... De Luna et al recently reported a favorable outcome of an acute chest syndrome (ACS) related to a SARS‐Cov‐2 infection treated with tocilizumab (TCZ), in ...

4. uchicagomedicine.org uchicagomedicine.org/find-a-clinical-trial/clinical-trial/irb220277

CLINICAL TRIAL / NCT05640271 The investigators are evaluating the role of a low dose of tocilizumab in treating acute chest syndrome in patients with sickle cell disease.

5. centerwatch.com centerwatch.com/clinical-trials/listings/NCT06818266/efficacy-and-safety-of-tocilizumab-for-acute-chest-syndrome-treatment-in-patients-with-sickle-cell-disease

Efficacy and Safety of Tocilizumab for Acute Chest ... The purpose of this study is to determine whether a single infusion of tocilizumab is effective in reducing the time to successful weaning ...

6. trialx.com trialx.com/clinical-trials/listings/269364/tocilizumab-for-acute-chest-syndrome/

Tocilizumab for Acute Chest Syndrome Clinical, laboratory, and patient-reported outcome data will be collected during their admission and compared between arms. ... How safe are clinical trials?