NCT05158387已完成3 期
A Phase III, Multicentre, Randomised, Double-blind, Chronic-dosing, Parallel-group, Placebo-controlled Study to Evaluate the Efficacy and Safety of Two Dose Regimens of Tozorakimab in Participants With Symptomatic Chronic Obstructive Pulmonary Disease (COPD) With a History of COPD Exacerbations (TITANIA)
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 1,172
- 试验地点
- 212
- 主要终点
- Annualized rate of moderate to severe COPD exacerbations in participants who are former smokers.
研究概览
简要总结
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 participants with symptomatic COPD and history of ≥ 2 moderate or ≥ 1 severe exacerbation of COPD in the previous 12 months. Participants should be receiving optimised treatment with maintenance inhaled therapy (ICS/LABA/LAMA triple therapy, or dual therapy if triple is not considered appropriate) in stable doses throughout at least 3 months prior to enrolment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
盲法说明
unblinded administrator/pharmacist
入排标准
- 年龄范围
- 40 Years 至 130 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participant must be ≥ 40 years of age and capable of giving signed informed consent.
- •Documented diagnosis of COPD for at least one year prior to enrolment.
- •Post BD FEV1/FVC < 0.70 and post-BD FEV1 >20% of predicted normal value.
- •Documented history of ≥ 2 moderate or ≥ 1 severe COPD exacerbations within 12 months prior to enrolment.
- •Documented optimized inhaled dual or triple therapy at a stable dose for at least 3 months prior to enrolment.
- •Smoking history of ≥ 10 pack-years.
- •CAT total score ≥10, with each of the phlegm (sputum) and cough items with a score ≥ 2
排除标准
- •Clinically important pulmonary disease other than COPD.
- •Radiological findings suggestive of a respiratory disease other than COPD that is significantly contributing to the participant's respiratory symptoms.
- •Current diagnosis of asthma, prior history of asthma, or asthma-COPD overlap. Childhood history of asthma is allowed and defined as asthma diagnosed and resolved before the age of
- •Any unstable disorder, including, but not limited to, cardiovascular, gastrointestinal, hepatic, renal, neurological, musculoskeletal, infectious, endocrine, metabolic, haematological, psychiatric disorder, major physical and/or cognitive impairment that could affect safety, study findings or participants ability to complete the study.
- •COPD exacerbation, within 2 weeks prior to randomization, that was treated with systemic corticosteroids and/or antibiotics, and/or led to hospitalization.
- •Active significant infection within the 4 weeks prior to randomization, pneumonia within 6 weeks prior to randomization, or medical condition that predisposes the participant to infection.
- •Suspicion of, or confirmed, ongoing SARS-CoV-2 infection.
- •Significant COVID-19 illness within the 6 months prior to enrolment.
- •Unstable cardiovascular disorder.
- •Diagnosis of cor pulmonale, pulmonary arterial hypertension and/or right ventricular failure.
- •History of known immunodeficiency disorder, including a positive test for HIV-1 or HIV
- •History of positive test or treatment for hepatitis B or hepatitis C (except for cured hepatitis C)
- •Evidence of active liver disease, including jaundice during screening.
- •Malignancy, current or within the past 5 years, except for adequately treated non-invasive basal cell and squamous cell carcinoma of the skin and cervical carcinoma-in-situ treated with apparent success more than one year prior to enrolment. Suspected malignancy or undefined neoplasms.
- •Participants who have evidence of active TB.
- •Participants that have previously received tozorakimab.
- •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.
- •Active vaping of any products or using smoked marijuana within the 6 months prior to randomization and during the study.
研究组 & 干预措施
Placebo
Placebo Comparator
Dosing subcutaneously with equivalent volume to tozorakimab
干预措施: Placebo (Drug)
Tozorakimab Dose 1
Experimental
Dosing subcutaneously tozorakimab Dose 1 and placebo
干预措施: Tozorakimab (Drug)
Tozorakimab Dose 2
Experimental
Dosing subcutaneously tozorakimab Dose 2
干预措施: Tozorakimab (Drug)
结局指标
主要结局
Annualized rate of moderate to severe COPD exacerbations in participants who are former smokers.
时间窗: over 52 weeks
The primary endpoint will be assessed first in the primary population (former smokers with symptomatic COPD and a history of exacerbations, on optimised treatment with maintenance inhaled therapy \[triple therapy, or dual therapy if triple is not considered appropriate\]) and then assessed in the overall population of participants.
次要结局
- Presence of anti-drug antibodies.(over 60 weeks)
- Annualized rate of moderate to severe COPD exacerbations in former or current smokers.(over 52 weeks)
- Time to first moderate to severe COPD exacerbation in former smokers.(over 52 weeks)
- Mean change from baseline in pre-BD, pre-dose trough FEV1 (mL) in former smokers.(Week 52, or over 52 weeks)
- Percentage of responders achieving MCID in E-RS:COPD total score in former smokers(Week 52)
- Percentage of responders achieving MCID in E-RS:COPD total score in the overall population of current and former smokers.(Week 52)
- Mean change from baseline in E-RS:COPD total score in former smokers.(over 52 weeks)
- Mean change from baseline in E-RS:COPD total score in the overall population of current and former smokers.(over 52 weeks)
- Mean change from baseline in pre-BD, pre-dose trough FEV1 (mL) in the overall population of current and former smokers.(Week 52, or over 52 weeks)
- Percentage of responders achieving MCID in SGRQ total score in former smokers.(Week 52)
- Percentage of responders achieving MCID in SGRQ total score in the overall population of current and former smokers.(Week 52)
- Annualized rate of severe COPD exacerbations in former smokers.(over 52 weeks)
- Change from baseline in CAT total score.(Week 52)
- Annualized rate of healthcare resource utilization in former smokers.(over 52 weeks)
- Mean change from baseline in SGRQ total score from in the overall population of current and former smokers.(over 52 weeks)
- Time to first severe COPD exacerbation in former smokers.(over 52 weeks)
- Mean change from baseline in SGRQ total score from in former smokers.(over 52 weeks)
- Percentage of participants with a decrease in CAT total score in former smokers.(Week 52)
- Proportion of participants having ≥ 1 healthcare resource utilization type in former smokers.(over 52 weeks)
- The change from baseline in mean number of puffs per day in rescue use in former smokers.(over 52 weeks)
- Trough serum concentrations of tozorakimab.(over 52 weeks)
研究者
研究点 (212)
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