Tozorakimab for COPD

(PROSPERO Trial)

Recruiting at 299 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

Trial Summary

What is the purpose of this trial?

This trial is testing Tozorakimab, a medication that aims to reduce lung inflammation, in adults aged 40 and older with COPD. The goal is to see if it can help them breathe better and have fewer symptoms.

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.

What data supports the effectiveness of the drug Tozorakimab for COPD?

The research suggests that monoclonal antibodies (mABs), like those targeting inflammation in COPD, can moderately reduce the risk of exacerbations (flare-ups) in COPD patients. While specific data on Tozorakimab is not provided, similar treatments like mepolizumab have shown benefits in reducing exacerbations in patients with high eosinophil counts, indicating potential effectiveness for Tozorakimab in similar patient groups. ^{1 2 3 4 5}

What makes the drug Tozorakimab unique for treating COPD?

Tozorakimab (MEDI-3506) is unique for treating COPD because it targets the interleukin-6 (IL-6) pathway, which is involved in inflammation, potentially offering a novel approach compared to standard COPD treatments that primarily focus on bronchodilation and symptom relief. ^{6 7 8 9 10}

Eligibility Criteria

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.

I can follow all study requirements and procedures.

Any clinically significant disorder or abnormal findings (clinical, laboratory, instrumental, etc) or major physical and/or cognitive impairment - which, in the opinion of the Investigator, may put the participant at risk because of his/her participation in the study or impact the interpretation of the study results, or otherwise make the participation of the participant inappropriate

Timeline

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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 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]

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 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 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 (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]

References

1. England pubmed.ncbi.nlm.nih.gov

Emerging biological therapies for treating chronic obstructive pulmonary disease: A pairwise and network meta-analysis. [2019]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Mepolizumab for Eosinophil-Associated COPD: Analysis of METREX and METREO. [2021]

3. New Zealand pubmed.ncbi.nlm.nih.gov

In vitro modeling of COPD inflammation and limitation of p38 inhibitor - SB203580. [2018]

4. England pubmed.ncbi.nlm.nih.gov

Precision medicine in COPD: review of mepolizumab for eosinophilic COPD. [2020]

5. England pubmed.ncbi.nlm.nih.gov

Current Perspectives on Biological Therapy for COPD. [2023]

6. Germany 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. [2020]

7. England 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. [2020]

8. England pubmed.ncbi.nlm.nih.gov

A Review of Recent Advances Using Tocilizumab in the Treatment of Rheumatic Diseases. [2023]

9. Greece pubmed.ncbi.nlm.nih.gov

Anti-proliferative action of IL-6R-targeted antibody tocilizumab for non-small cell lung cancer cells. [2020]

10. England pubmed.ncbi.nlm.nih.gov

Subcutaneous tocilizumab in rheumatoid arthritis: findings from the common-framework phase 4 study programme TOZURA conducted in 22 countries. [2022]