Tozorakimab for COPD

(TITANIA Trial)

Not currently recruiting at 219 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: AstraZeneca

Must be taking: Inhaled therapy

Disqualifiers: Asthma, Cardiovascular, Infection, Cancer, 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: Unknown

Duration: 52 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness and safety of a medication called tozorakimab for individuals with COPD, a lung disease that makes breathing difficult. The study involves administering two different doses of tozorakimab as subcutaneous injections and comparing them to a placebo, which contains no active drug. It targets individuals with COPD who have experienced at least two moderate or one severe flare-up in the past year and are on stable inhaler therapy. Participants should have a history of smoking, issues with coughing and phlegm, and a COPD diagnosis for at least a year. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial requires participants to continue their current inhaled COPD medications at stable doses for at least 3 months before joining the study. It doesn't specify if you need to stop other medications, so it's best to discuss with the trial team.

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

Research has shown that tozorakimab has been well tolerated by participants in other studies. These studies found no major safety concerns, suggesting it is relatively safe for people. Participants did not report serious side effects, indicating the treatment did not cause significant problems. This information helps reassure about the safety of tozorakimab. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for COPD?

Most treatments for COPD, like bronchodilators and inhaled corticosteroids, aim to relieve symptoms and prevent flare-ups by opening airways and reducing inflammation. But Tozorakimab works differently, targeting a specific protein involved in inflammation. This means it has the potential to more directly address the root cause of inflammation in COPD. Researchers are excited because Tozorakimab could offer a new way to manage COPD, potentially improving lung function and quality of life for patients who don't fully benefit from existing treatments.

What evidence suggests that this trial's treatments could be effective for COPD?

Research shows that tozorakimab, a type of medication, may help treat COPD (Chronic Obstructive Pulmonary Disease). Earlier studies found that tozorakimab reduces symptoms and decreases the number of flare-ups in people with breathing problems. In this trial, participants will receive either Tozorakimab Dose 1, Tozorakimab Dose 2, or a placebo. Early results suggest that both doses of tozorakimab can help manage symptoms in those with COPD. This treatment targets a protein called IL-33, which is involved in inflammation, and may help reduce lung damage and improve breathing. Overall, these early findings offer hope that tozorakimab could be an effective option for people living with COPD. ^{1 4 6 7 8}

Are You a Good Fit for This Trial?

Adults over 40 with COPD, a smoking history of at least 10 pack-years, and who've had multiple flare-ups in the past year can join. They must have been on stable inhaled therapy for 3 months and give consent. Excluded are those with other significant lung diseases, recent drug use or infections, unstable health conditions, certain cancer histories, or previous tozorakimab treatment.

Inclusion Criteria

Your lung function test shows a specific ratio and amount of air flow that is not within normal range.

I've had at least 2 moderate or 1 severe COPD flare-ups in the last year.

I have had at least 2 moderate or 1 severe COPD flare-ups in the last year.

Exclusion Criteria

I have asthma, had it in the past, or have asthma-COPD overlap.

I have active tuberculosis.

Any clinically significant abnormal findings in physical examination, vital signs, ECG, or laboratory testing during the screening period, which in the opinion of the investigator may put the participant at risk because of their participation in the study, or may influence the results of the study, or the participant's ability to complete the entire duration of the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive subcutaneous doses of tozorakimab or placebo for COPD management

52 weeks

Regular visits for dosing and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• MEDI3506
• Tozorakimab

Trial Overview The trial is testing two doses of Tozorakimab against a placebo in people with COPD to see if it's safe and effective. Participants will receive injections under the skin while continuing their usual inhaler medications.

How Is the Trial Designed?

Group I: Tozorakimab Dose 2 Experimental Treatment 1 Intervention

Dosing subcutaneously tozorakimab Dose 2

Group II: Tozorakimab Dose 1 Experimental Treatment 1 Intervention

Dosing subcutaneously tozorakimab Dose 1 and placebo

Group III: Placebo Placebo Group 1 Intervention

Dosing subcutaneously with equivalent volume to tozorakimab

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 meta-analysis of 1136 patients from the METREX and METREO trials, mepolizumab significantly reduced the annual rate of moderate to severe exacerbations in COPD patients with elevated blood eosinophil counts by 18% compared to placebo.

The study found that higher blood eosinophil counts were associated with greater efficacy of mepolizumab, suggesting that patients with eosinophil counts of ≥150 cells/µL at screening or ≥300 cells/µL in the prior year are more likely to benefit from this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mepolizumab for Eosinophil-Associated COPD: Analysis of METREX and METREO. Pavord, ID., Chapman, KR., Bafadhel, M., et al.[2021]

In a study involving 66 COPD patients and 15 healthy controls, it was found that COPD serum significantly increased pro-inflammatory markers like CCL5 and TNF-α while decreasing the anti-inflammatory marker IL-10, indicating a strong pro-inflammatory effect in COPD.

The p38 inhibitor SB203580 was able to suppress inflammation by reducing CCL5 and TNF-α levels and increasing IL-10 production, but its effectiveness was limited in COPD patients, suggesting that there are other inflammatory mechanisms at play that do not involve p38 signaling.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vitro modeling of COPD inflammation and limitation of p38 inhibitor - SB203580. Meng, A., Zhang, X., Wu, S., et al.[2018]

Mepolizumab has been shown to significantly reduce the rate of exacerbations in patients with severe COPD who frequently experience flare-ups and have elevated blood eosinophil levels.

This treatment represents a step forward in precision medicine for COPD, allowing for more targeted therapies based on individual patient characteristics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Precision medicine in COPD: review of mepolizumab for eosinophilic COPD. Long, G., Wall, J.[2020]

In early rheumatoid arthritis, treatment with tocilizumab (TCZ) combined with methotrexate (MTX) showed a greater reduction in disease activity (DAS28) and higher remission rates compared to the traditional MTX plus prednisone treatment over 24 months, with TCZ+MTX showing a mean difference of -0.62 in DAS28 scores.

While TCZ-based strategies demonstrated better outcomes in terms of disease activity and remission, some of these benefits may be influenced by the effect of TCZ on acute phase reactants, suggesting that the observed improvements might not be solely due to the treatment's efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Initiating tocilizumab, with or without methotrexate, compared with starting methotrexate with prednisone within step-up treatment strategies in early rheumatoid arthritis: an indirect comparison of effectiveness and safety of the U-Act-Early and CAMERA-II treat-to-target trials. Verhoeven, MM., de Hair, MJ., Tekstra, J., et al.[2020]

In a phase IIIb trial involving 288 patients with moderate-to-severe rheumatoid arthritis (RA), weekly subcutaneous tocilizumab (TCZ-SC) significantly reduced disease activity as measured by the Clinical Disease Activity Index (CDAI) within just 2 weeks, with sustained improvements observed up to 52 weeks.

TCZ-SC demonstrated low immunogenicity and no unexpected toxicities, making it a safe option for patients, and the study suggests that home administration of the treatment is feasible after a median of just 2 doses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Subcutaneous tocilizumab alone or with a csDMARD in rheumatoid arthritis patients: subanalysis of Italian data from a multicenter phase IIIb/IV trial. Bazzichi, L., Nacci, F., Sinigaglia, L., et al.[2020]

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]

In a pooled analysis of the TOZURA study involving 1804 patients with moderate to severe rheumatoid arthritis (RA), subcutaneous tocilizumab (TCZ-SC) demonstrated significant efficacy in reducing disease activity, with similar results whether used alone or in combination with conventional synthetic DMARDs.

The safety profile of TCZ-SC was confirmed, with a low rate of serious adverse events (5.8%) and a withdrawal rate of 13.9%, indicating that TCZ-SC is a safe and effective treatment option for patients who have not responded adequately to previous therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Subcutaneous tocilizumab in rheumatoid arthritis: findings from the common-framework phase 4 study programme TOZURA conducted in 22 countries. Choy, E., Caporali, R., Xavier, R., et al.[2022]

Tocilizumab, an anti-IL-6R antibody, significantly inhibited the growth of non-small cell lung cancer (NSCLC) cells by 10-40%, showing effectiveness comparable to traditional chemotherapy drugs like methotrexate and 5-fluorouracil.

The treatment with tocilizumab led to an accumulation of NSCLC cells in the sub-G1 phase, indicating apoptosis induction, and suggested activation of the NFκB pathway, highlighting its potential as a new therapeutic option for NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-proliferative action of IL-6R-targeted antibody tocilizumab for non-small cell lung cancer cells. Kim, NH., Kim, SK., Kim, DS., et al.[2020]

Monoclonal antibody (mAB) therapies have a moderate effect on reducing the risk of exacerbations in chronic obstructive pulmonary disease (COPD), but they do not significantly improve lung function (FEV1) or quality of life (SGRQ).

In eosinophilic COPD patients, the IL-5 antagonist mepolizumab was found to reduce exacerbation risk, while benralizumab showed effectiveness in improving both lung function and quality of life, highlighting the potential of targeting IL-5 pathways in specific patient populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Emerging biological therapies for treating chronic obstructive pulmonary disease: A pairwise and network meta-analysis. Rogliani, P., Matera, MG., Puxeddu, E., et al.[2019]

Current treatments for COPD, primarily bronchodilators and corticosteroids, mainly focus on symptom relief and do not effectively address the underlying inflammation or prevent disease progression.

There is a need for new anti-inflammatory therapies, and targeted biotherapy may improve COPD management by identifying novel biomarkers and understanding the inflammatory processes involved in the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current Perspectives on Biological Therapy for COPD. Yadav, AK., Gu, W., Zhang, T., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05166889

NCT05166889 | Efficacy and Safety of Tozorakimab in ... The purpose of this Phase III study is to evaluate the efficacy and safety of tozorakimab Dose 1 and Dose 2 administered subcutaneously (SC) in adult ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12256803/

A phase 2a trial of the IL-33 monoclonal antibody ... FRONTIER-4 (NCT04631016) was a phase 2a, randomised, double-blind, placebo-controlled study to assess the efficacy, safety and tolerability of tozorakimab in ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04631016

Study Details | NCT04631016 | A Phase II, Randomized, ... This is a research study to determine the efficacy and safety of investigational drug MEDI3506 for the treatment of adult participants with Chronic Obstructive ...

4. astrazenecaclinicaltrials.com astrazenecaclinicaltrials.com/study/D9180C00003

Efficacy and Safety of Tozorakimab in Symptomatic ... The purpose of this Phase III study is to evaluate the efficacy and safety of tozorakimab Dose 1 and Dose 2 administered subcutaneously (SC) in adult ...

5. nature.com nature.com/articles/s41598-023-36642-y

Tozorakimab (MEDI3506): an anti-IL-33 antibody that ... Tozorakimab is currently being investigated in multiple inflammatory diseases including a phase 3 study in acute respiratory failure ( ...

6. atsjournals.org atsjournals.org/doi/abs/10.1164/ajrccm.2025.211.Abstracts.A1373

Safety Profile of Tozorakimab (an Anti-IL-33 Monoclonal ... Conclusions: Across all four FRONTIER studies, tozorakimab was well tolerated with no safety concerns identified. Several phase 3 studies are ongoing for ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38115209/

A Randomized Phase I Study of the Anti-Interleukin-33 ... Tozorakimab is a human monoclonal antibody that neutralizes interleukin (IL)-33. IL-33 is a broad-acting epithelial alarmin cytokine upregulated in lung tissue.

8. ascpt.onlinelibrary.wiley.com ascpt.onlinelibrary.wiley.com/doi/10.1002/cpt.3147

A Randomized Phase I Study of the Anti‐Interleukin‐33 ... A randomized phase I study of the anti-interleukin-33 antibody tozorakimab in healthy adults and patients with chronic obstructive pulmonary disease.