Tozorakimab for Viral Pneumonia

(TILIA Trial)

Recruiting at 315 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: AstraZeneca

Disqualifiers: Fungal infection, Parasitic infection, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: 1

Duration: Single dose

2870 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called tozorakimab to determine its effectiveness for people with viral lung infections who require extra oxygen. The goal is to see if tozorakimab can prevent death or stop the illness from worsening, compared to a placebo (a dummy treatment with no active drug). Participants will receive either tozorakimab or a placebo to compare outcomes. This trial may suit individuals hospitalized with a viral lung infection who need extra oxygen for breathing. As a Phase 3 trial, it represents the final step before FDA approval, offering participants a chance to contribute to potentially life-saving research.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, since the study involves adding tozorakimab to the standard of care (SoC), it's likely you can continue your current treatments. Please consult with the trial coordinators for specific guidance.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that tozorakimab, a monoclonal antibody, has been tested in earlier studies. These studies examined its effects on individuals with illnesses similar to viral pneumonia. Although detailed safety information is not available, the Phase 3 trial status indicates that earlier studies found it reasonably safe. In the early stages of research, scientists ensure a treatment is safe for people before testing it on larger groups.

While specific details on side effects for tozorakimab are not available, its progression to this advanced stage suggests it has been well-tolerated by patients so far. Prospective trial participants can expect that earlier research would have addressed any major safety issues. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Tozorakimab is unique because it targets the immune system's response to viral pneumonia rather than the virus itself. While most treatments for viral pneumonia focus on antiviral medications or supportive care like oxygen therapy, tozorakimab is an antibody that aims to reduce inflammation by blocking a specific protein in the body. Researchers are excited about tozorakimab because it has the potential to quickly calm the excessive immune response that can lead to severe lung damage, potentially leading to better outcomes for patients.

What evidence suggests that tozorakimab might be an effective treatment for viral pneumonia?

Research has shown that tozorakimab, which participants in this trial may receive, might help treat viral lung infections. In earlier studies, patients with COVID-19 who took tozorakimab had a lower risk of serious health problems. This treatment targets individuals needing extra oxygen due to viral pneumonia. By reducing lung inflammation, tozorakimab aims to prevent the condition from worsening. Although more research is needed, early results are promising for those at risk of severe lung issues. ^{1 2 3 4 5}

Are You a Good Fit for This Trial?

This trial is for adults over 18 hospitalized with a viral lung infection needing extra oxygen but not on mechanical ventilation or ECMO. They must have low blood oxygen levels and signs of the infection on chest scans, use extra muscles to breathe, or have a high respiratory rate.

Inclusion Criteria

I have low oxygen levels and signs of a lung infection or difficulty breathing.

I need extra oxygen to help me breathe.

I am in the hospital due to a lung infection caused by a virus.

Exclusion Criteria

My low oxygen levels are due to a non-infectious lung injury or an external cause.

You are currently using a ventilator or an ECMO machine at the time of randomization.

I do not have a fungal, parasitic lung infection, lung abscess, or severe lung infection.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single dose of tozorakimab or placebo as an add-on to Standard of Care (SoC) for viral lung infection requiring supplemental oxygen

Single dose

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness, including ICU admission, ventilator use, and survival outcomes

60 days

What Are the Treatments Tested in This Trial?

Interventions

• Placebo
• Tozorakimab

Trial Overview The study tests Tozorakimab's effectiveness when added to standard care in preventing death or the need for intensive breathing support (IMV/ECMO) in patients with severe viral lung infections requiring supplemental oxygen.

How Is the Trial Designed?

Group I: Tozorakimab Experimental Treatment 1 Intervention

Approximately 2870 participants will be randomized in a 1:1 ratio. Arm 1 (n=approximately 1435) will receive a single dose of tozorakimab.

Group II: Placebo Placebo Group 1 Intervention

Approximately 2870 participants will be randomized in a 1:1 ratio. Arm 2 (n=approximately 1435) will receive matching placebo.

Who Is Running the Clinical Trial?

AstraZeneca

Lead Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Published Research Related to This Trial

In a phase II study involving 448 rheumatoid arthritis patients, ixekizumab significantly improved symptoms in both biologics-naive patients and those with inadequate responses to TNF inhibitors, showing a clear dose-response relationship at week 12.

The safety profile of ixekizumab was comparable to other biologic treatments, with similar rates of adverse events, although infections were slightly more common in the ixekizumab group, with no serious infections reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II randomized study of subcutaneous ixekizumab, an anti-interleukin-17 monoclonal antibody, in rheumatoid arthritis patients who were naive to biologic agents or had an inadequate response to tumor necrosis factor inhibitors. Genovese, MC., Greenwald, M., Cho, CS., et al.[2016]

In a study of 40 COVID-19 patients with cytokine storm syndrome, a single dose of tocilizumab (8 mg/kg) effectively maintained serum concentrations above the therapeutic threshold for 16 days, indicating its efficacy in managing IL-6-mediated hyperinflammation.

The research suggests that a fixed dose of 400 mg of tocilizumab could be sufficient for treatment, potentially preventing overtreatment and conserving resources without compromising efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single dose tocilizumab for COVID-19 associated cytokine storm syndrome: Less is more. Boone, NW., Moes, DJAR., Ramiro, S., et al.[2023]

In a study involving 1681 patients with rheumatoid arthritis who had inadequate responses to previous treatments, tocilizumab showed rapid and sustained efficacy, with significant improvements in disease activity scores over 24 weeks.

The treatment was generally safe, with a low discontinuation rate of 5.1% due to adverse events, although patients who had recently used TNF inhibitors experienced a higher rate of adverse events compared to those who had never used them.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tocilizumab in patients with active rheumatoid arthritis and inadequate responses to DMARDs and/or TNF inhibitors: a large, open-label study close to clinical practice. Bykerk, VP., Ostör, AJ., Alvaro-Gracia, J., et al.[2021]

In a study of 322 rheumatoid arthritis patients treated with tocilizumab (TCZ), 57.5% achieved low disease activity and 38.1% reached disease remission after 6 months, indicating TCZ's effectiveness in managing RA symptoms.

The safety profile of TCZ was generally good, with 28.6% of patients experiencing drug-related adverse events, primarily mild issues like hypercholesterolemia and leucopenia, and only 7.5% discontinuing treatment due to safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tocilizumab in the treatment of patients with rheumatoid arthritis in real clinical practice: results of an Italian observational study. Caporali, R., Idolazzi, L., Bombardieri, S., et al.[2018]

Tocilizumab, an interleukin-6 receptor antagonist, has shown significant clinical improvements in rheumatoid arthritis patients at doses greater than 4 mg/kg, with the most effective dose being 8 mg/kg, which also reduces joint damage as seen in radiographic measures.

While tocilizumab is effective, it is associated with common adverse effects such as liver function abnormalities, infections, and neutropenia, highlighting the need for further research to better understand its safety profile and optimal use in treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tocilizumab: an interleukin-6 receptor inhibitor for the treatment of rheumatoid arthritis. Plushner, SL.[2016]

In a phase II study involving 119 Asian patients with moderately-to-severely active rheumatoid arthritis who had not responded to anti-TNF therapy, olokizumab (OKZ) showed significant improvements in disease activity scores compared to placebo after 12 weeks.

The safety profile of OKZ was comparable to that of placebo, with similar rates of adverse events and no reported deaths, indicating that it is a safe option for patients in this category.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of olokizumab in Asian patients with moderate-to-severe rheumatoid arthritis, previously exposed to anti-TNF therapy: Results from a randomized phase II trial. Takeuchi, T., Tanaka, Y., Yamanaka, H., et al.[2022]

Tocilizumab, when given at the approved dose of 8 mg/kg every 4 weeks in combination with methotrexate, significantly improves rheumatoid arthritis symptoms, with a higher likelihood of achieving important clinical outcomes compared to placebo, including a 38.8% response rate versus 9.6% for placebo.

While tocilizumab treatment was associated with a higher incidence of any adverse events and increased cholesterol levels, it did not lead to a significant increase in serious adverse effects or withdrawals due to adverse events, indicating a favorable safety profile overall.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tocilizumab for rheumatoid arthritis: a Cochrane systematic review. Singh, JA., Beg, S., Lopez-Olivo, MA.[2018]

In a 12-week Phase IIb study involving 221 patients with moderate-to-severe rheumatoid arthritis who had previously failed TNF inhibitor therapy, olokizumab (OKZ) significantly reduced disease activity (measured by DAS28(CRP)) compared to placebo, indicating its efficacy as a treatment option.

OKZ demonstrated similar efficacy to tocilizumab (TCZ) across multiple endpoints, with most adverse events being mild or moderate, suggesting a favorable safety profile consistent with other drugs in its class.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of olokizumab in patients with rheumatoid arthritis with an inadequate response to TNF inhibitor therapy: outcomes of a randomised Phase IIb study. Genovese, MC., Fleischmann, R., Furst, D., et al.[2023]

In a study of 21 patients with COVID-19 pneumonia treated with the IL-6 receptor antagonist tocilizumab (TCZ), 62% of survivors and 25% of non-survivors had preexisting medical conditions, highlighting the importance of patient selection in treatment outcomes.

No serious adverse effects were reported, indicating that TCZ can be administered safely in this patient population, especially when given at a critical stage of the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A single-center experience in use of tocilizumab in COVID-19 pneumonia in India. Joshi, A., Kumar M, K., Kumar, A., et al.[2023]

Tocilizumab (TCZ) is an effective treatment for various inflammatory conditions, including rheumatoid arthritis and giant cell arteritis, with strong evidence supporting its long-term safety and efficacy from both clinical trials and real-world studies.

Recent studies have shown that subcutaneous TCZ can lead to significant improvements in patients with systemic sclerosis, indicating its potential for broader applications in other immunological diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Review of Recent Advances Using Tocilizumab in the Treatment of Rheumatic Diseases. Rubbert-Roth, A., Furst, DE., Nebesky, JM., et al.[2023]

Tocilizumab (TCZ) has been shown to improve survival odds in COVID-19 patients, particularly those with severe disease, based on a systematic review of nine randomized clinical trials involving over 6,400 patients.

The analysis indicated a significant reduction in all-cause mortality at 28-30 days, with a survival odds ratio of 0.84, suggesting TCZ could be an effective treatment option for severe COVID-19, although further studies are needed to confirm these results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Use of Tocilizumab in Patients with COVID-19: A Systematic Review, Meta-Analysis and Trial Sequential Analysis of Randomized Controlled Studies. Maraolo, AE., Crispo, A., Piezzo, M., et al.[2021]

In a meta-analysis of 19 randomized controlled trials involving 7,835 patients with rheumatoid arthritis, abatacept was found to significantly increase the likelihood of achieving an ACR70 response compared to tocilizumab, with a relative risk of 2.217.

Rituximab did not show a significant difference in achieving ACR70 response compared to abatacept, indicating that while all three treatments are options for refractory RA, abatacept may offer superior efficacy over tocilizumab under similar study conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Compared efficacy of rituximab, abatacept, and tocilizumab in patients with rheumatoid arthritis refractory to methotrexate or TNF inhibitors agents: a systematic review and network meta-analysis. Pugliesi, A., de Oliveira, AB., Oliveira, AB., et al.[2023]

In a study of 1162 patients with early rheumatoid arthritis, tocilizumab (TCZ) combined with methotrexate (MTX) or as a standalone treatment led to significantly higher remission rates compared to placebo, with 45% and 39% of patients achieving remission at week 24, respectively.

The 8 mg/kg TCZ+MTX group showed notable improvements in radiographic disease progression and physical function at week 52, indicating that TCZ is effective for early RA treatment, with a safety profile similar to that of other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tocilizumab in early progressive rheumatoid arthritis: FUNCTION, a randomised controlled trial. Burmester, GR., Rigby, WF., van Vollenhoven, RF., et al.[2022]

Citations

1. astrazenecaclinicaltrials.com astrazenecaclinicaltrials.com/study/D9185C00001

Efficacy and Safety of Tozorakimab in Patients Hospitalised ... The purpose of this study is to evaluate the effect of tozorakimab, as an add-on to SoC in patients with viral lung infection requiring supplemental oxygen.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05624450

Study Details | NCT05624450 | Efficacy and Safety of ... The purpose of this study is to evaluate the effect of tozorakimab, as an add-on to SoC in patients with viral lung infection requiring supplemental oxygen.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10588785/

A randomised phase 2a study to investigate the effects of ... Overall, these results highlight the possibility that tozorakimab could be an effective therapy for patients hospitalised with COVID-19 who are at risk of acute ...

4. astrazenecaclinicaltrials.com astrazenecaclinicaltrials.com/study/D9180C00002

A Phase II, Randomized, Double-blind, Placebo-controlled ... This is a research study to determine the efficacy and safety of investigational drug MEDI3506 for the treatment of adult participants with Chronic ...

5. withpower.com withpower.com/trial/phase-3-infections-11-2022-0c127

Tozorakimab for Viral Pneumonia (TILIA Trial) This trial is testing tozorakimab, a medication that may help people with severe viral lung infections who need extra oxygen.