Tozorakimab for COPD
(TITANIA Trial)
Recruiting in Palo Alto (17 mi)
+158 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 3
Recruiting
Sponsor: AstraZeneca
Must be taking: Inhaled therapy
Disqualifiers: Asthma, Cardiovascular, Infection, Cancer, others
Pivotal Trial (Near Approval)
Prior Safety Data
Trial Summary
What is the purpose of this trial?
This trial is testing injections of a drug called tozorakimab in adults with COPD who have frequent flare-ups. These patients are already on other inhaled treatments but still experience significant symptoms. The drug aims to reduce lung inflammation and prevent these flare-ups.
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.
What data supports the effectiveness of the drug Tozorakimab for COPD?
Research on similar treatments, like mepolizumab, shows that targeting specific inflammatory pathways can reduce exacerbation rates in COPD patients with high eosinophil levels. This suggests that Tozorakimab, which may work in a similar way, could potentially be effective for certain COPD patients.12345
What makes the drug Tozorakimab unique for treating COPD?
Eligibility Criteria
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.
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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.
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Trial Timeline
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
Treatment Details
Interventions
- MEDI3506 (Monoclonal Antibodies)
- Tozorakimab (Monoclonal Antibodies)
Trial OverviewThe 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.
Participant Groups
3Treatment groups
Experimental Treatment
Placebo Group
Group I: Tozorakimab Dose 2Experimental Treatment1 Intervention
Dosing subcutaneously tozorakimab Dose 2
Group II: Tozorakimab Dose 1Experimental Treatment1 Intervention
Dosing subcutaneously tozorakimab Dose 1 and placebo
Group III: PlaceboPlacebo Group1 Intervention
Dosing subcutaneously with equivalent volume to tozorakimab
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Research SiteLivonia, MI
Research SiteSalt Lake City, UT
Research SiteAndalusia, AL
Research SiteBoston, MA
More Trial Locations
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Who Is Running the Clinical Trial?
AstraZenecaLead Sponsor
References
Mepolizumab for Eosinophil-Associated COPD: Analysis of METREX and METREO. [2021]A pre-specified meta-analysis of individual patient data from the 52-week METREX and METREO trials, which investigated mepolizumab for chronic obstructive pulmonary disease (COPD) in patients with blood eosinophil counts ≥150 cells/µL (screening) or ≥300 cells/µL (prior year) and frequent exacerbations, enables more robust characterization of mepolizumab efficacy in COPD and exploration of the relationship between blood eosinophil count and treatment responses.
Emerging biological therapies for treating chronic obstructive pulmonary disease: A pairwise and network meta-analysis. [2019]Inflammation in chronic obstructive pulmonary disease (COPD) is often corticosteroid resistant and, thus, alternative anti-inflammatory approaches are needed. Since it is still not clear whether blocking specific pro-inflammatory factors may provide clinical benefit in COPD, we have performed a meta-analysis to quantify the impact of monoclonal antibodies (mABs) targeting the cytokine/chemokine-mediated inflammation in COPD. A pairwise and network meta-analyses were performed by extracting data from randomized clicnial trials on COPD concerning the impact of mABs vs. placebo on the risk of exacerbation, forced expiratory volume in 1 s (FEV1), and St. George's Respiratory Questionnaire (SGRQ). Data on the interleukin (IL)-1β antagonist canakinumab, IL-1R1 antagonist MEDI8986, IL-5 antagonist mepolizumab, IL-5R antagonist benralizumab, IL-8 antagonist ABX-IL8, and TNF-α antagonist infliximab were found. Overall, mAB therapy had a moderate impact on the risk exacerbation, but not on FEV1 and SGRQ. The pairwise meta-analysis performed in eosinophilic patients, and the network approach, indicated that mepolizumab elicited a beneficial effect against the risk of exacerbation, whereas benralizumab was more effective in improving both FEV1 and SGRQ. This study demonstrates that targeting the pathway activated by IL-5 may have a beneficial impact in eosinophilic COPD patients.
In vitro modeling of COPD inflammation and limitation of p38 inhibitor - SB203580. [2018]Systemic inflammation and steroid resistance are the hallmarks of COPD. We examined the impact of p38 inhibitor (SB203580) in in vitro assays of systemic inflammation using pulmonary cells and patients' sera.
Precision medicine in COPD: review of mepolizumab for eosinophilic COPD. [2020]Mepolizumab can reduce exacerbation rates in those with frequently exacerbating, severe COPD and raised blood eosinophils; this represents a further advance in precision medicine for COPD and targeted therapies http://ow.ly/uklu30m4YcU.
Current Perspectives on Biological Therapy for COPD. [2023]Chronic obstructive pulmonary disease (COPD) is a chronic, complex, and heterogeneous condition with significant mortality, morbidity, and socioeconomic burden. Given the heterogeneity, the current management of COPD, which mainly relies on bronchodilators and corticosteroids, cannot consider all COPD populations. Moreover, the present treatment modalities are directed at minimizing symptoms and reducing the risk of a future attack, but they exhibit few meaningful anti-inflammatory activities in preventing and reducing disease progression. Therefore, new anti-inflammatory molecules are needed to manage COPD better. Use of targeted biotherapy may obtain better results by increasing understanding of the underlying inflammatory process and identifying new biomarkers. In this review, we focus briefly on study of the underlying inflammatory process in the pathogenesis of COPD for better identification of novel target biomarkers, and we describe a novel class of anti-inflammatory biologics that are already under evaluation for their use in managing COPD.
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]Methotrexate (MTX), often combined with low moderately dosed prednisone, is still the cornerstone of initial treatment for early rheumatoid arthritis (RA). It is not known how this strategy compares with initial treatment with a biological. We therefore compared the effectiveness of tocilizumab (TCZ), or TCZ plus MTX (TCZ+MTX) with MTX plus 10 mg prednisone (MTX+pred), all initiated within a treat-to-target treatment strategy in early RA.
A Review of Recent Advances Using Tocilizumab in the Treatment of Rheumatic Diseases. [2023]Tocilizumab (TCZ) is the first humanized anti-interleukin-6 (IL-6) receptor monoclonal antibody approved for the treatment of patients with rheumatoid arthritis (RA), Castleman's disease, polyarticular and systemic juvenile idiopathic arthritis, and, most recently, giant cell arteritis as well as for the treatment of chimeric antigen receptor T cell therapy-induced cytokine release syndrome. The global clinical development program for TCZ provides a wealth of clinical data on intravenous TCZ, and more recent studies in patients with RA have provided evidence characterizing the role of intravenous TCZ as monotherapy in early disease and led to the introduction of a subcutaneous formulation of TCZ. In addition, recently published open-label extension and observational studies continue to support the long-term efficacy and safety of TCZ in both clinical trial and real-world settings. Given the involvement of IL-6-mediated signaling in inflammatory disorders, TCZ is also being investigated in other immunological diseases. In particular, a phase 2 trial on the safety and efficacy of subcutaneous TCZ in adults with systemic sclerosis shows clinically relevant improvements in skin sclerosis and lung function in these patients. Another anti-IL-6 receptor agent, sarilumab, targeting the IL6 receptor alpha subunit, was recently approved for the treatment of patients with RA, although long-term data for this biologic are not yet published. In this article we review the placement of TCZ in current treatment guidelines; recent clinical trial data, including quality of life in patients with RA; recent updates to the TCZ safety profile; recent investigations of TCZ in other immunological diseases; and the clinical development of other novel IL-6-targeted agents.
Anti-proliferative action of IL-6R-targeted antibody tocilizumab for non-small cell lung cancer cells. [2020]In the present study we analyzed the anti-proliferative effect of tocilizumab, a humanized recombinant monoclonal interleukin 6 receptor (IL-6R) antibody, against non-small cell lung cancer (NSCLC) cells, including A549, H460, H358 and H1299 cells. The cell cycle distribution of NSCLCs was analyzed using fluorescence-activated cell sorting and gene expression using quantitative polymerase chain reaction. Cell lysates treated with tocilizumab were immunoblotted with antibodies against signal transducer and activator of transcription 3 (STAT3), phospho-STAT3, extracellular-signal-regulated kinases (ERK), phospho-ERK, nuclear factor κB (NFκB) and phospho-NFκB. Significant growth inhibition of NSCLC cells was observed following treatment with tocilizumab. Proliferation was significantly decreased by approximately 10-40% in A549, H460, H1299 and H358 cells, with an inhibition rate that was comparable with that of the typical anticancer drugs methotrexate and 5-fluorouracil. NSCLC cell populations were accumulated in the sub-G1 phase by treatment with tocilizumab. Western blot analyses revealed a possible activation of the NFκB pathway by tocilizumab. Overall, these data indicate that tocilizumab has anticancer potency via apoptosis induction as an agonistic IL-6R regulator. Therefore, we suggest that this anti-IL-6R antibody may be utilized as a new targeting molecule for NSCLC therapies.
Subcutaneous tocilizumab in rheumatoid arthritis: findings from the common-framework phase 4 study programme TOZURA conducted in 22 countries. [2022]The aim of this pooled analysis of the TOZURA study programme was to evaluate the efficacy and safety of subcutaneous tocilizumab (TCZ-SC) as monotherapy or in combination with conventional synthetic DMARDs (csDMARDs) in patients with moderate to severe RA who had an inadequate response to csDMARD or anti-TNF agent therapy or who were MTX naïve.
Subcutaneous tocilizumab alone or with a csDMARD in rheumatoid arthritis patients: subanalysis of Italian data from a multicenter phase IIIb/IV trial. [2020]To assess, in a setting close to real life, the efficacy and safety of weekly subcutaneous tocilizumab (TCZ-SC) 162 mg, alone or with a conventional synthetic DMARD (csDMARD), in moderate-to-severe RA patients with inadequate response to DMARDs or anti-TNFα drugs. This national, multicenter, open-label, phase IIIb trial is part of an umbrella study (TOZURA). Patients were treated for 52 weeks followed by 8 weeks drug-free to evaluate immunogenicity. The primary end point was the Clinical Disease Activity Index (CDAI) change from baseline at weeks 2 and 24. Other efficacy parameters, including sleep quality, and the safety and immunogenicity were also assessed up to week 52. Of 288 patients enrolled in 43 Italian centers, 78.8% received TCZ-SC (86.8% females; mean age 54.7 ± 12.1 years; mean disease duration 7.8 ± 7.5 years; DMARD-IRs 94.7%). Of these, 78.0% completed the 52-week period and 52.0% received concomitant methotrexate. TCZ-SC yielded a significant reduction in median CDAI from baseline already at week 2, which progressed up to week 24 and remained stable thereafter (P