Tozorakimab for COPD

(PROSPERO Trial)

Recruiting at 262 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: AstraZeneca

Must not be taking: Immunosuppressants, Corticosteroids, Biologics, others

Disqualifiers: Severe allergies, Cognitive impairment, 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: 104 weeks

1869 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a medication called Tozorakimab to determine its effectiveness in improving symptoms and ensuring safety for people with COPD, a lung condition that makes breathing difficult. Participants will receive either one of two different doses of Tozorakimab or a placebo (a substance with no active medication) via injection. This continuation study is primarily for those who completed treatment in previous related studies and still experience COPD symptoms. As a Phase 3 trial, it represents the final step before FDA approval, offering participants the opportunity to contribute to a potentially groundbreaking treatment for COPD.

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

The trial does not specify if you need to stop taking your current medications, but it does mention that chronic use of immunosuppressive medications is not allowed. It's best to discuss your specific medications with the study team.

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

Research has shown that tozorakimab is generally safe for humans. Studies, including several ongoing ones, have not identified any major safety issues. Specifically, four different studies consistently reported that participants did not experience significant side effects. These findings suggest that tozorakimab could be a safe option for people with COPD, a lung condition that makes breathing difficult. Since this information is based on previous research, participants should ask questions and discuss any concerns with the trial team. ^{1 2 3 4 5}

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

Tozorakimab is unique because it targets the underlying inflammation associated with COPD by being an antibody specifically designed to inhibit interleukin-33, a protein involved in inflammatory responses. Unlike traditional COPD treatments such as bronchodilators and corticosteroids, which primarily address symptoms, Tozorakimab aims to tackle the inflammation at its source. Researchers are excited about this treatment because it offers a new mechanism of action that could provide more effective management of COPD and potentially improve patient outcomes by reducing exacerbations and hospitalizations.

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

Research shows that tozorakimab is a new treatment under testing for chronic obstructive pulmonary disease (COPD). It targets IL-33, a protein that causes inflammation and may contribute to COPD symptoms. Earlier studies have shown promising results, indicating that tozorakimab can reduce inflammation and help patients breathe better. Initial trials suggested that the treatment is generally safe and may reduce the severity of COPD symptoms. These findings indicate that tozorakimab could effectively manage COPD, but more studies are needed to confirm these results. Participants in this trial will receive either one of two doses of tozorakimab or a placebo to further evaluate its effectiveness and safety. ^{2 3 6 7 8}

Are You a Good Fit for This Trial?

This trial is for adults with symptomatic COPD who've completed the OBERON or TITANIA studies without early discontinuation. They must have taken their last dose within 12 weeks and agree to continue using contraception. Excluded are those with significant health issues, involvement in study planning, inability to follow study requirements, known allergies to trial drugs, or use of certain immunosuppressives.

Inclusion Criteria

I am able to understand and sign the consent form.

Participants who have completed the treatment period and have not been prematurely discontinued from IP in the predecessor studies

Women who could become pregnant must have a negative urine pregnancy test at the first visit.

Exclusion Criteria

I regularly take or will need to take medication that affects my immune system.

Involvement in the planning and/or conduct of the study (applies to both staff employed by the Sponsor and/or staff at the study site)

I can follow all study requirements and procedures.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Tozorakimab or placebo subcutaneously to evaluate long-term efficacy and safety in COPD

104 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Tozorakimab

Trial Overview The trial tests Tozorakimab's long-term safety and effectiveness against a placebo in managing COPD symptoms. It's a phase 3 extension from previous studies (OBERON/TITANIA), maintaining a double-blind approach where neither participants nor researchers know who receives the actual drug versus placebo.

How Is the Trial Designed?

Group I: Tozorakimab Dose 2 Experimental Treatment 1 Intervention

Injection subcutaneously Tozorakimab via pre-filled syringe.

Group II: Tozorakimab Dose 1 Experimental Treatment 1 Intervention

Injection subcutaneously Tozorakimab via pre-filled syringe.

Group III: Placebo Placebo Group 1 Intervention

Injection subcutaneously with equivalent volume to Tozorakimab via pre-filled syringe.

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 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]

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 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]

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 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]

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]

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]

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]

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]

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. 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 ...

7. astrazenecaclinicaltrials.com astrazenecaclinicaltrials.com/study/AZ-RU-00008

A study to investigate efficacy and safety of tozorakimab ... The purpose of this study is to investigate lung function parameters, composite endpoint for exacerbations in chronic obstructive pulmonary disease ...

8. 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 ...