Tozorakimab for COPD

(MIRANDA Trial)

Not currently recruiting at 409 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: AstraZeneca

Must be taking: Inhaled maintenance therapy

Disqualifiers: Asthma, Active infection, Malignancy, 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 new treatment, tozorakimab, for people with COPD, a lung condition that makes breathing difficult. The researchers aim to determine if this treatment can reduce flare-ups in those who have experienced frequent or severe symptoms in the past year. Participants will receive either tozorakimab or a placebo (an inactive substance) via injection. This trial suits individuals with COPD who have had at least two moderate or one severe flare-up in the last year and are already on inhaled maintenance therapy. As a Phase 3 trial, this research represents the final step before FDA approval, offering participants the opportunity to contribute to a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial requires participants to continue their current inhaled maintenance therapy for COPD, such as ICS/LABA/LAMA triple therapy or dual therapy, for at least 3 months before joining the study. The protocol does not specify if other medications need to be stopped.

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

Research has shown that tozorakimab is generally safe for people. In several studies, including four known as the FRONTIER studies, researchers found no major safety issues. Participants taking tozorakimab did not experience significant or unusual side effects.

The latest safety results for tozorakimab are very positive, supporting its use for breathing problems. So far, evidence suggests that tozorakimab maintains a strong safety record. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for COPD?

Tozorakimab is unique because it offers a novel approach to treating COPD by targeting and inhibiting interleukin-33 (IL-33), a protein involved in inflammatory responses. Most current COPD treatments, like bronchodilators and corticosteroids, mainly focus on relieving symptoms and reducing inflammation broadly. Tozorakimab's specific action on IL-33 could potentially lead to more effective control of inflammation, addressing a root cause rather than just the symptoms. This targeted mechanism is what excites researchers, as it might offer improved outcomes for patients with COPD.

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

Research has shown that tozorakimab, a type of medication, holds promise for treating COPD. It reduces lung inflammation by blocking a protein called IL-33, which is part of the immune system. Early studies found that tozorakimab can lower the number and severity of COPD flare-ups. Specifically, participants in this trial who received tozorakimab experienced fewer flare-ups compared to those who received a placebo. These results suggest that tozorakimab could be a helpful option for managing COPD symptoms. ^{1 2 4 6 7}

Are You a Good Fit for This Trial?

Adults over 40 with COPD, having had at least one severe or two moderate flare-ups in the past year. They must have a significant cough and phlegm, poor lung function tests but not too severe, and a history of heavy smoking. Excluded are those with asthma, serious heart or other health problems, recent infections including COVID-19 or lung resections, immune deficiencies, certain liver diseases or cancer within five years.

Inclusion Criteria

Your total score for the COPD Assessment Test is 10 or higher, and both the phlegm and cough items each have a score of 2 or higher.

Your lung function test shows a specific level of air flow after using a bronchodilator.

You have smoked for at least 10 packs of cigarettes per year.

Exclusion Criteria

I haven't had a serious infection or pneumonia in the weeks before joining the study.

My scans show a lung problem not related to COPD causing my symptoms.

My scans show lung nodules that may be cancerous, but I haven't followed up on them yet.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive subcutaneous administration of tozorakimab or placebo for COPD management

52 weeks

Regular visits for subcutaneous administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Long-term follow-up

Participants are monitored for long-term outcomes such as exacerbations and mortality

Approximately 3 years

What Are the Treatments Tested in This Trial?

Interventions

• Tozorakimab

Trial Overview The trial is testing Tozorakimab's effectiveness for COPD symptoms against a placebo. Participants will receive injections under the skin while continuing their usual inhaler treatments. The study aims to see if Tozorakimab can reduce flare-ups and improve breathing.

How Is the Trial Designed?

Group I: Tozorakimab Experimental Treatment 1 Intervention

Dosing subcutaneously tozorakimab

Group II: 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 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]

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]

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, 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]

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]

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]

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]

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]

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]

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. clinicaltrialsarena.com clinicaltrialsarena.com/analyst-comment/ats-2025-tozorakimab-positive-results-frontier-studies/

ATS 2025: Tozorakimab's safety reinforced with positive ... Tozorakimab's safety profile was favourable and well tolerated. The latest set of safety results could bolster the asset's profile in the respiratory space.