A Phase IIa, Multicenter, Randomized, Placebo-Controlled, Double-Blind Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of MTPS9579A in Patients With Asthma Requiring Inhaled Corticosteroids and a Second Controller
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 135
- 试验地点
- 27
- 主要终点
- Time to First Composite Asthma Exacerbations (CompEX) Event
研究概览
简要总结
This is a Phase IIa, randomized, placebo-controlled, double-blind, multicenter, two-arm study to evaluate the efficacy, safety, and pharmacokinetics of MTPS9579A as an add-on therapy in patients with uncontrolled moderate to severe asthma who are receiving daily ICS therapy and at least one of the following additional controller medications: long-acting beta-agonist (LABA), leukotriene modulator (leukotriene modifier [LTM] or leukotriene receptor antagonist [LTRA]), long-acting muscarinic antagonist (LAMA), or long-acting theophylline preparation.
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)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Documented physician-diagnosed asthma for at least 12 months prior to screening
- •Treatment with asthma controller therapy (daily ICS [fluticasone propionate or equivalent] and at least one additional controller therapy [LABA, LAMA, LTM/LTRA]) for >= 3 months prior to screening, with no changes within 4 weeks prior to screening or during the screening period and no anticipated changes in controller dosing regimens throughout the study
- •Documented history of >= 2 asthma exacerbation within the 12 months prior to screening while on daily ICS maintenance therapy
- •For women of childbearing potential: agreement to remain abstinent or use contraception For men: agreement to remain abstinent or use a condom, and agreement to refrain from donating sperm
排除标准
- •History or evidence of vocal cord dysfunction, reactive airways dysfunction syndrome, hyperventilation associated with panic attacks, or other mimics of asthma
- •History or evidence of significant respiratory disease other than asthma, including occupational asthma, aspirin-sensitive asthma, asthma-chronic obstructive pulmonary disease (COPD) overlap syndrome, bronchiolitis, interstitial lung disease, or COPD
- •Current smoker, electronic cigarette (e-cigarette) user, former smoker with smoking history of > 10 pack-years, former e-cigarette user with an e-cigarette history of at least daily use for >=10 years, or unwilling to abstain from smoking and/or e-cigarette use from the time of consent through the completion of the study
- •History or evidence of any clinically significant medical condition/disease or abnormalities in laboratory tests that, in the investigator's judgment, precludes the patient's safe participation and completion of the study, or interferes with the conduct and interpretation of the study
- •Active malignancy or history of malignancy within 5 years of screening, except for appropriately treated non-melanoma skin carcinoma, cervical carcinoma in situ, breast ductal carcinoma in situ, or Stage I uterine cancer
- •Pregnant or breastfeeding, or intending to become pregnant during the study or within 60 days after the final dose of MTPS9579A
- •Positive for TB at screening
研究组 & 干预措施
MTPS9579A
干预措施: MTPS9579A (Drug)
Placebo
干预措施: Placebo (Drug)
结局指标
主要结局
Time to First Composite Asthma Exacerbations (CompEX) Event
时间窗: Randomization [Week 2] to end of treatment (EOT) [Week 50]
CompEX is defined as time from randomization to first asthma exacerbation or diary worsening during the treatment period. Asthma exacerbation was defined as new or increased asthma symptoms (wheezing, coughing, dyspnea, chest tightness, and/or nighttime awakenings due to these symptoms) that resulted in one or both of the following: Hospitalization or emergency department visit with administration of systemic corticosteroid treatment; Treatment with systemic corticosteroids for at least 3 days, or a long-acting depot corticosteroid preparation with a therapeutic effectiveness of at least 3 days. Diary worsening is based on the occurrence of prespecified changes in the following six parameters: morning peak expiratory flow rate (PEFR), evening PEFR, morning symptom score, evening symptom score, morning short-acting rescue therapy use, and evening short-acting rescue therapy use. Hazard ratio was used for the analysis.
次要结局
- Steady State Cmax of MTPS9579A(2-hour post-dose on Week 14)
- Maximum Time to Serum Concentration (Tmax) of MTPS9579A(Pre-dose and 2-hour post-dose on Week 2)
- Trough Serum Concentration (Ctrough) Accumulation Ratio of MTPS9579A(Predose on Weeks 6 and 14)
- Rate of Asthma Exacerbations(Randomization [Week 2] to Week 50)
- Time to First Asthma Exacerbation(Randomization [Week 2] to Week 50)
- Absolute Change From Randomization in Pre-Bronchodilator Forced Expiratory Volume in 1 Second (FEV1) at Week 50(Randomization [Week 2] to Week 50)
- Relative Percent Change From Randomization in Pre-Bronchodilator FEV1 at Week 50(Randomization [Week 2] to Week 50)
- Absolute Change From Randomization in Fractional Exhaled Nitric Oxide (FeNO) at Week 50(Randomization [Week 2] to Week 50)
- Steady State Ctrough of MTPS9579A(Pre-dose on Week 14)
- Relative Percent Change From Randomization in FeNO at Week 50(Randomization [Week 2] to Week 50)
- Percentage of Participants With Adverse Events(Up to approximately Week 58)
- Area Under Concentration-Time Curve for the First Dosing Interval (AUClast) of MTPS9579A(Randomization [Week 2] to Week 6)
- Maximum Serum Concentration (Cmax) for the First Dosing Interval of MTPS9579A(2-hour post-dose on Week 2)
- Percentage of Participants With Anti-Drug Antibodies (ADA) to MTPS9579A(Pre-dose Week 54)