A Double-Blind, Placebo-Controlled, Parallel-Group Study to Assess the Efficacy, Safety, and Tolerability of CAT-354
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 14
- 试验地点
- 41
- 主要终点
- Change From Baseline in Doubling Concentration of Methacholine at Day 28
研究概览
简要总结
To investigate the effects of CAT-354 on airway hyper-responsiveness (AHR) in uncontrolled asthma.
详细描述
This is a randomized, stratified, double-blind, placebo-controlled, multicenter, multinational study in subjects with uncontrolled asthma despite optimal treatment. Following confirmation of eligibility, subjects will be randomly assigned on Day 0, to 1 of 4 dose groups 1 mg/kg CAT-354, 5 mg/kg CAT-354, 10 mg/kg CAT or Placebo to match all doses of CAT-354. Doses of the assigned treatment will be administered on three occasions 28 days apart. Subjects will be assessed for efficacy, including airway hyper-responsiveness (AHR), safety, pharmacokinetic, pharmacodynamics and immunogenicity until Day 84 post-first dose.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Signed and dated written informed consent is obtained prior to any study related procedure taking place
- •Women either infertile (example [e.g.], hysterectomized, sterile or post-menopausal with amenorrhea of least 1 year duration) or who are practicing an acceptable form of birth control
- •Uncontrolled (refractory) asthma despite treatment with a minimum dose of 800 microgram (mcg) beclomethasonedipropionate or equivalent inhaled corticosteroid per day plus 1 or more additional controller, that is, long-acting beta-agonist, leukotriene antagonist or theophylline. Oral corticosteroids (not parenteral) as additional treatment at any dose are acceptable
- •A forced expiratory volume in 1 second (FEV1) acceptable for airway hyper-responsiveness (AHR) challenge tests (greater than 60 percent of predicted normal) on the challenge days
- •A provocative concentration of methacholine causing a 20 percent fall in FEV1 (PC20) less than 4 milligram per milliliter (mg/mL)
- •Aged 18-80 years
- •A 12-lead electrocardiogram (ECG) with no-clinically significant abnormalities
- •Clinical chemistry, hematology and urinalysis results within the laboratory reference ranges or deemed not clinically significant by the Investigator
- •Body weight of less than 130 kilogram (kg)
- •No other clinically significant abnormality on history and clinical examination
- •Able to comply with the requirements of the protocol.
排除标准
- •Experienced a severe exacerbation within 28 days preceding Day -28/-14 to Day 0
- •Onset of uncontrolled seasonal allergy symptoms within 28 days preceding Day -28/-14 to Day 0
- •Subjects with a history of allergic rhinitis, seasonal allergy or esophagitis must be optimally controlled and remain on a stable treatment regimen during the study
- •Participation in another study within 5 half-lives or 3 months of the start of this study, whichever is the longer
- •Lower respiratory tract infection within 6 weeks of Day -28/-14 to Day 0
- •Current smokers or ex-smokers with greater than 10 pack-years
- •Blood donation (more than 550 mL) in the previous 2 months
- •Excessive intake of alcohol (as judged by the Investigator) or evidence of drug or solvent abuse
- •Subjects with a physician-diagnosis of any other significant lung disease, including a primary diagnosis of chronic obstructive pulmonary disease or bronchiectasis, or lung cancer, sarcoidosis, tuberculosis, pulmonary fibrosis and cystic fibrosis
- •Concurrent medication from Day -28/-14 to Day 0 (Screening visit) and for the duration of the study with any of the prohibited medications
- •Significant, uncontrolled disease including serious psychological disorders, chronic renal failure, uncontrolled hypertension
- •systolic blood pressure greater than 200 millimeters of mercury (mmHg), or diastolic blood pressure greater than 100 mmHg, heart disease, psoriasis requiring treatment and subjects who have had a heart attack or stroke within the 3 months preceding Day -28/-14 to Day 0, or who have a known aneurysm
- •Onset of uncontrolled seasonal allergy symptoms within 28 days preceding Day -28/-14 to Day 0
- •Subjects with a history of allergic rhinitis, seasonal allergy or esophagitis must be optimally controlled and remain on a stable treatment regimen during the study
- •Any factor which, in the opinion of the Investigator, would jeopardize the evaluation or safety or be associated with poor adherence to the protocol (that is, inability to complete study diary, perform peak expiratory flow (PEF) measurements)
- •The subject's primary care physician recommends the subject should not take part in the study
- •Known hypersensitivity to CAT-354 or its components, to the challenge agents used in the study or to related drugs.
研究组 & 干预措施
Placebo
Placebo matched to CAT-354 intravenous infusion over 60 minutes on Day 0, 28 and 56.
干预措施: Placebo (Other)
CAT-354 1 mg/kg
CAT-354 1 milligram per kilogram (mg/kg) of body weight intravenous infusion over 60 minutes on Day 0, 28 and 56.
干预措施: CAT-354 1 mg/kg (Biological)
CAT-354 5 mg/kg
CAT-354 5 mg/kg of body weight intravenous infusion over 60 minutes on Day 0, 28 and 56.
干预措施: CAT-354 5 mg/kg (Biological)
CAT-354 10 mg/kg
CAT-354 5 mg/kg of body weight intravenous infusion over 60 minutes on Day 0, 28 and 56
干预措施: CAT-354 10 mg/kg (Other)
结局指标
主要结局
Change From Baseline in Doubling Concentration of Methacholine at Day 28
时间窗: Baseline and Day 28
Change in doubling concentrations of methacholine was calculated as Log2 PC20 (Visit x) - Log2 PC20 (Baseline), where x was the post-baseline assessment (Day 28) and PC20 was provocative concentration of methacholine causing 20 percent fall in forced expiratory volume in 1 second (FEV1). FEV1 was the maximal volume of air exhaled in the first second of a forced expiration from a position of full inspiration. Change in doubling concentration was summarized for sub-therapeutic dose (placebo and CAT-354 1 milligram/kilogram \[mg/kg\]) and therapeutic dose (CAT-354 5 mg/kg and CAT-354 10 mg/kg), as per planned analysis.
次要结局
- Forced Expiratory Volume in 1 Second (FEV1)(Predose, 30 minutes and 6 hours post-end of infusion on Day 0, 28 and 56; Day 4, 14, 35, 63, 84 or early termination (any time before Day 84))
- Forced Expiratory Volume in 1 Second (FEV1) as Percentage of Forced Vital Capacity (FVC)(Predose, 30 minutes and 6 hours post-end of infusion on Day 0, 28 and 56; Day 4, 14, 35, Day 63, 84 or early termination (any time before Day 84))
- Maximum Observed Serum Concentration (Cmax) for CAT-354(Predose, 10 minutes and 6 hours post-end of infusion on Day 0, 28 and 56)
- Post-bronchodilator Forced Expiratory Volume in 1 Second (FEV1)(Day 0 to 84)
- Number of Participants With Diary Data(Day 0, 4, 14, 28, 35, 56, 63 to Day and 84)
- Forced Vital Capacity (FVC)(Predose, 30 minutes and 6 hours post-end of infusion on Day 0, 28 and 56; Day 4, 14, 35, 63, 84 or early termination (any time before Day 84))
- Number of Participants With Exacerbations(Day 0 to Day 84)
- Morning Peak Flow and Peak Flow Variability(Day 0 to Day 84)
- Asthma Control Questionnaire (ACQ) Total Score(Baseline, Day 28, 56, 84 or early termination (any time before Day 84))
- Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)(Day 0 to 84)
- Change From Baseline in Doubling Concentration of Methacholine at Day 56, 84 or Early Termination(Baseline, Day 56, 84 or early termination (any time before Day 84))
- Minimum Observed Serum Concentration (Cmin) for CAT-354(Predose, 10 minutes and 6 hours post-end of infusion on Day 0, 28 and 56)
- Accumulation Ratio for CAT-354 (RA)(Predose, 10 minutes and 6 hours post-end of infusion on Day 0, 28 and 56)
- Area Under the Serum Concentration Time Curve From Time Zero to Last Measurable Concentration (AUC [0 - t]) for CAT-354(Predose, 10 minutes and 6 hours post-end of infusion on Day 0, 28 and 56)
- Adult Asthma Quality of Life (QoL) Questionnaire Final Score(Day 0, 28, 84 or early termination (any time before Day 84))