NCT04631016已完成2 期
A Phase II, Randomized, Double-blind, Placebo-controlled Study to Assess the Efficacy, Safety and Tolerability of MEDI3506 in Participants With Moderate to Severe Chronic Obstructive Pulmonary Disease and Chronic Bronchitis (FRONTIER 4)
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 137
- 试验地点
- 1
- 主要终点
- Change From Baseline to Week 12 in Pre-bronchodilator Forced Expiratory Volume in 1 Second (Pre-BD FEV1) as Measured in Clinic
研究概览
简要总结
This is a research study to determine the efficacy and safety of investigational drug MEDI3506 for the treatment of adult participants with Chronic Obstructive Pulmonary Disease and Chronic Bronchitis.
详细描述
Study D9180C00002 is a Phase II, randomised, double-blind, placebo-controlled, parallel group, proof of concept study to evaluate the efficacy and safety of MEDI3506 in adult participants with moderate to severe Chronic Obstructive Pulmonary Disease and Chronic Bronchitis.
Approximately 85 sites globally will participate in this study. Approximately 144 participants will be randomized to 2 treatment groups in a 1:1 ratio to receive MEDI3506 or placebo.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Investigational product only will be prepared and administrated by unmasked personnel.
入排标准
- 年龄范围
- 40 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Provision of informed consent.
- •Participant must be 40 to 80 years of age inclusive, at the time of signing the informed consent form (ICF).
- •Participants who are current or ex-smokers with a tobacco history of >= 10 pack-years.
- •Participants who have a documented history of COPD for at least 1 year.
- •Participants who have a post-BD FEV1/FVC < 0.70 and a post-BD FEV1 >= 20% and < 80% predicted normal value at screening. Centralized spirometry will be used for this criteria assessment.
- •Participants who have a physician confirmed participant history of chronic bronchitis as defined as presence of cough and sputum on most days for >= 3 months/year in at least the 2 year period immediately prior to study visit 1 (SV1) (Screening).
- •Participants who have an average BCSS score of >= 2 in cough and >= 2 in sputum domains assessed over 14 days preceding SV
- •Participants who have a documented stable regimen of dual therapy or triple therapy for >= 3 months prior to enrolment; there should have been no change in treatment after the previous exacerbation prior to entering into the study. Where dual therapy consists of inhaled corticosteroids (ICS) + long-acting beta 2 agonist (LABA) or LABA + long-acting muscarinic receptor antagonist (LAMA), and triple therapy consists of ICS + LABA + LAMA.
- •Participants who have a documented history of >= 1 moderate or severe AECOPD requiring systemic corticosteroids and/or antibiotics for at least 3 days duration (or 1 injection of depot formulation), or hospitalization for reason of AECOPD in the previous 24 months.
- •Body mass index within the range 18 to 40 kg/m^2 (inclusive).
- •Female participants of childbearing potential, must have negative pregnancy tests.
- •Male and female participants must follow protocol contraceptive guidance.
排除标准
- •Participants with a positive diagnostic nucleic acid test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at screening. Participants with mild or asymptomatic disease could be rescreened.
- •Participants with a significant coronavirus disease 2019 (COVID-19) illness within 6 months of enrolment.
- •As judged by the investigator, any evidence of any active medical or psychiatric condition or other reason which in the investigator's opinion makes it undesirable for the participant to participate in the study.
- •Current or past diagnosis of asthma which persisted beyond age of 25 years.
- •Clinically important pulmonary disease other than COPD, radiological findings, and/or laboratory findings suggestive of a respiratory disease other than COPD that is contributing to the participant's respiratory symptoms.
- •Increased pre-BD FEV1 at randomization visit (SV3) compared to Screening SV1 of >= 400 mL or >= 25% of SV1 FEV
- •Any other clinically relevant abnormal findings on physical examination, laboratory testing; or chest CT scan, which in the opinion of the investigator or medical monitor may compromise the safety of the participant in the study or interfere with evaluation of the study intervention or reduce the participant's ability to participate in the study.
- •Chest CT scan findings requiring further investigation or repeat CT surveillance before SV
- •A family history of heart failure.
- •A LVEF < 45% measured by echocardiogram.
- •History of a clinically significant infection (viral, bacterial, or fungal) within 4 weeks.
- •History of, or a reason to believe a participant has a history of, drug or alcohol abuse within the past 2 years prior to screening.
- •Participants with a recent history of, or who have a positive test for, infective hepatitis or unexplained jaundice, or participants who have been treated for hepatitis B, hepatitis C, or human immunodeficiency virus (HIV).
- •Evidence of active or untreated latent tuberculosis (TB).
- •Change in smoking status in 12 weeks prior to enrolment or intention to change smoking status between enrolment and end of follow-up.
- •Participants currently receiving background therapy that is not approved by regulatory authorities in the country of study for COPD are not eligible for the study.
- •History of treatment with cardiotoxic medications (eg, as part of cancer therapy) including thiazolidinedione's.
- •Treatment with broad spectrum antibiotic within 4 weeks prior to randomization (Day 1).
- •Receiving any of the prohibited concomitant medications as specified in the clinical study protocol (CSP).
- •Inability to perform technically acceptable spirometry.
- •Additional inclusion and exclusion criteria's applies.
研究组 & 干预措施
Tozorakimab
Experimental
Participants received 7 doses of subcutaneous (SC) tozorakimab Dose Level 1 injection once every 4 weeks (Q4W).
干预措施: Tozorakimab (Drug)
Placebo
Placebo Comparator
Participants received 7 doses of SC placebo injection matched to tozorakimab once Q4W.
干预措施: Placebo (Other)
结局指标
主要结局
Change From Baseline to Week 12 in Pre-bronchodilator Forced Expiratory Volume in 1 Second (Pre-BD FEV1) as Measured in Clinic
时间窗: Baseline (Day -35 to Day -28) through Week 12
The mean change from baseline in Pre-BD FEV1 at Week 12 (tozorakimab - placebo) estimated using a repeated measures mixed effects analysis of covariance measures was estimated. Data available from all visits up to and including Week 12, irrespective of whether the participant discontinued study drug or received reliever therapy was considered. FEV1 was measured by spirometry at clinic.
次要结局
- Serum Tozorakimab Concentration(Post-dose at Study Weeks 2, 4, 12, 20, 24, 28, 32, and 36)
- Number of Participants With Positive Anti-drug Antibodies (ADA) to Tozorakimab(Pre-dose at Study Weeks 0 (baseline) and post-dose at Study Weeks 2, 4, 12, 20, 24, 28, 32, and 36)
- Number of Participants Experiencing First Chronic Obstructive Pulmonary Disease Composite Exacerbations (COPDCompEx) Event(Baseline (Day -35 to Day -28) through Week 28)
- Change From Baseline to Week 12 in 4-weekly Mean Evaluating Respiratory Symptoms of COPD (E-RS:COPD) Total Score(Baseline (from evening of Study Day -14 to the morning of Study Day 1) through Week 12)
- Change From Baseline to Week 12 in Mean Breathlessness, Cough and Sputum Scale (BCSS) Score (Over the Previous 4 Weeks)(Baseline (from evening of Study Day -14 to the morning of Study Day 1) through Week 12)
- Change From Baseline to Week 12 in Cough Visual Analogue Scale (VAS) Score(Baseline (from evening of Study Day -14 to the morning of Study Day 1) through Week 12)
- Change From Baseline to Week 12 in Saint George's Respiratory Questionnaire (SGRQ) Total Score(Baseline (from evening of Study Day -14 to the morning of Study Day 1) through Week 12)
- Change From Baseline to Week 12 in AO Parameter-Area Under the Reactance Curve (AX)(Baseline (Study Day 1) and Week 12)
- Percentage of Participants With a Decrease in SGRQ Total Score of >= 4 Points From Baseline to Week 12(Baseline (from evening of Study Day -14 to the morning of Study Day 1) through Week 12)
- Change From Baseline to Week 12 in Airwave Oscillometry (AO) Parameters(Baseline (Study Day 1) and Week 12)
- Ratio to Baseline in Daily, Night-time, and Awake Time Cough Frequency at Week 12(Baseline (Day -21 to Day -7) and Week 12)
- Change From Baseline in Pre-BD FEV1 and Post-BD FEV1 Through Week 28 in Participants With Extent of Emphysema < 10%(Baseline (Week -5 to -4) through Week 28 post-dose)
- Number of Participants With Abnormal Vital Signs Reported as TEAEs(Day 1 through 253 days (maximum observed duration))
- Change From Baseline in Pre-BD FEV1 and Post-BD FEV1 Through Week 28 in Participants With Extent of Emphysema >= 10%(Baseline (Week -5 to -4) through Week 28 post-dose)
- Change From Baseline in Pre-BD and Post-BD Forced Vital Capacity (FVC) Through Week 28 in Participants With Extent of Emphysema < 10%(Baseline (Week -5 to -4) through Week 28 post-dose)
- Change From Baseline in Pre-BD and Post-BD FVC Through Week 28 in Participants With Extent of Emphysema >= 10%(Baseline (Week -5 to -4) through Week 28 post-dose)
- Number of Participants With Treatment Emergent Adverse Events (TEAEs), Treatment Emergent Serious Adverse Events (TESAEs), and TEAEs of Special Interest (TEAESIs)(Day 1 through 253 days (maximum observed duration))
- Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs(Day 1 through 253 days (maximum observed duration))
- Number of Participants With Abnormal Electrocardiograms (ECGs) Reported as TEAEs(Day 1 through 253 days (maximum observed duration))
- Change From Baseline in Left Ventricular Ejection Fraction (LVEF) as Measured by Echocardiogram(Baseline (Week -3 to -1) through Week 28)
- Change From Baseline in N-terminal Pro-brain Natriuretic Peptide (NT-proBNP) Level(Baseline (Day -35 to Day -28) through Week 28)
- Number of Participants With Coronavirus Disease 2019 (COVID-19) Related AEs and SAEs(Day 1 through 253 days (maximum observed duration))
- Number of Participants Seropositive for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)(Baseline (Week 0) through Week 28)
研究者
研究点 (1)
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