A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, 12-Week Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of ENV-294 in Adult Participants With Moderate-to-Severe Asthma
概览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- Enveda Therapeutics
- 入组人数
- 50
- 试验地点
- 9
- 主要终点
- Incidence and Severity of Adverse Events
概览
简要总结
This study will evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and potential efficacy of ENV-294 in adults with moderate to severe asthma who are receiving background treatment with inhaled corticosteroids (ICS) and long-acting beta₂-agonists (LABA).
Participants will take oral ENV-294 or placebo once daily for 12 weeks. The study includes a screening period of up to 28 days before randomization to confirm eligibility. Study visits and assessments will be conducted to monitor safety, measure drug levels in the blood, and evaluate effects on asthma control and lung function.
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
- •Able to read, understand, and sign an informed consent form before any study procedures.
- •Male or female adults aged 18 to 75 years with a physician diagnosis of moderate to severe asthma for at least 12 months.
- •Receiving stable treatment with an inhaled corticosteroid (ICS) plus a long-acting beta₂-agonist (LABA) for at least 2 months before screening.
- •Pre-bronchodilator FEV₁ between 50% and 80% of predicted normal at screening and baseline.
- •Demonstrated bronchodilator reversibility, defined as ≥12% and ≥200 mL improvement in FEV₁ (or ≥20% increase in peak expiratory flow) after short-acting bronchodilator use.
- •ACQ-5 score ≥1.25 and ≤3.0 at screening and baseline.
- •History of at least one asthma exacerbation in the past 12 months requiring systemic corticosteroids or hospitalization/emergency care.
排除标准
- •Had a moderate or severe asthma exacerbation within 4 weeks before screening.
- •Have a history of life-threatening asthma, including intubation or respiratory arrest.
- •Have any other significant pulmonary disease (e.g., COPD, bronchiectasis, pulmonary fibrosis, cystic fibrosis, tuberculosis, lung cancer, or eosinophilic syndromes).
- •Had bronchial thermoplasty within 2 years before screening.
- •Used biologic therapies for asthma (e.g., benralizumab, mepolizumab, reslizumab, omalizumab, dupilumab, or tezepelumab) within 6 months or 5 half-lives prior to baseline.
- •Require immunosuppressive medications or frequent systemic corticosteroids (more than 3 courses in the past 6 months).
- •Are current smokers or former smokers with \>10 pack-year history or who quit within 6 months before screening.
- •Have uncontrolled hypertension (systolic ≥160 mmHg or diastolic \>95 mmHg).
- •Have significant hepatic impairment or any other condition that, in the investigator's opinion, would interfere with study participation or interpretation of results.
研究组 & 干预措施
ENV-294 Treatment Arm
Participants will be treated with ENV-294 if they are randomized to this treatment arm.
干预措施: ENV-294 (Drug)
Placebo Arm
Participants will be treated with placebo (matching the appearance of ENV-294 active drug) if they are randomized to the placebo arm.
干预措施: Placebo (Drug)
结局指标
主要结局
Incidence and Severity of Adverse Events
时间窗: From first dose through approximately 16 weeks
Number and percentage of participants with treatment-emergent adverse events (AEs), serious adverse events (SAEs), and adverse events leading to discontinuation of study drug. Events will be summarized by severity and relationship to study treatment.
Change from baseline in hemaglobin.
时间窗: Baseline through approximately 16 weeks (end of study).
Assessment of change from baseline in hemoglobin concentration to evaluate the safety and tolerability of ENV-294.
Change from baseline in clinical chemistry laboratory values
时间窗: Baseline through approximately 16 weeks (end of study).
Evaluation of changes from baseline in serum clinical chemistry values - including electrolytes (sodium, potassium, chloride), liver function tests (ALT, AST, alkaline phosphatase, bilirubin), kidney function tests (creatinine, blood urea nitrogen), and glucose - to assess the safety and tolerability of ENV-294.
Change from baseline in red blood cell count
时间窗: Baseline through approximately 16 weeks (end of study)
Assessment of change from baseline in red blood cell (RBC) count to evaluate the safety and tolerability of ENV-294.
Change from baseline in platelet count
时间窗: Baseline through approximately 16 weeks (end of study)
Assessment of change from baseline in platelet count to evaluate the safety and tolerability of ENV-294.
Observed values, change from baseline, and percent change from baseline in heart rate (beats per minute) as a measure of safety and tolerability of ENV-294.
时间窗: Baseline through approximately 16 weeks (end of study).
Heart rate measured from 12-lead ECG recordings in beats per minute to assess cardiac safety and tolerability.
Observed values and change from baseline in coagulation parameters as primary measures of safety and tolerability of ENV-294.
时间窗: Baseline through approximately 16 weeks (end of study).
Coagulation tests include prothrombin time (PT), activated partial thromboplastin time (aPTT), and international normalized ratio (INR). Changes from baseline will be assessed to evaluate safety and tolerability of ENV-294.
Observed value, change from baseline, and percent change from baseline in systolic blood pressure (mmHg) as a measure of safety and tolerability.
时间窗: Baseline through approximately 16 weeks (end of study).
Systolic blood pressure measured in millimeters of mercury (mmHg) using standard clinical procedures at each study visit to assess safety and tolerability of ENV-294.
Observed values and change from baseline in urinalysis parameters as primary measures of safety and tolerability of ENV-294.
时间窗: Baseline through approximately 16 weeks (end of study).
Urinalysis parameters include color, clarity, specific gravity, pH, protein, glucose, ketones, blood, leukocytes, and microscopic evaluation, as applicable. Changes from baseline will be evaluated to assess safety and tolerability of ENV-294.
Observed values, change from baseline, and percent change from baseline in RR interval (milliseconds) as a measure of safety and tolerability of ENV-294.
时间窗: Baseline through treatment and end of study (approximately Week 16).
RR interval measured from 12-lead ECGs in milliseconds (ms) to assess cardiac safety and tolerability.
Observed values, change from baseline, and percent change from baseline in QRS duration (milliseconds) as a measure of safety and tolerability of ENV-294.
时间窗: Baseline through treatment and end of study (approximately Week 16).
QRS duration measured in milliseconds (ms) using standard 12-lead ECGs to assess cardiac conduction and safety.
Observed value, change from baseline, and percent change from baseline in heart rate (beats per minute) as a measure of safety and tolerability.
时间窗: Baseline through the treatment priod and end of study at approximately week 16.
Heart rate measured in beats per minute (bpm) using standard clinical procedures at each study visit to assess safety and tolerability of ENV-294.
Observed values, change from baseline, and percent change from baseline in PR interval (milliseconds) as a measure of safety and tolerability of ENV-294.
时间窗: Baseline through treatment and end of study (approximately Week 16).
PR interval measured in milliseconds (ms) using standard 12-lead ECGs to assess safety and tolerability.
Observed values, change from baseline, and percent change from baseline in QT interval (milliseconds) as a measure of safety and tolerability of ENV-294.
时间窗: Baseline through treatment and end of study (approximately Week 16).
QT interval measured in milliseconds (ms) using standard 12-lead ECGs to assess cardiac repolarization safety.
Observed values, change from baseline, and percent change from baseline in QTc Bazett (milliseconds) as a measure of safety and tolerability of ENV-294.
时间窗: Baseline through treatment and end of study (approximately Week 16).
QTc Bazett (QT corrected for heart rate using Bazett's formula) measured in milliseconds (ms) to evaluate cardiac safety.
Observed values, change from baseline, and percent change from baseline in QTc Fridericia (milliseconds) as a measure of safety and tolerability of ENV-294.
时间窗: Baseline through treatment and end of study (approximately Week 16).
QTc Fridericia (QT corrected for heart rate using Fridericia's formula) measured in milliseconds (ms) to evaluate cardiac safety.
Observed value, change from baseline, and percent change from baseline in diastolic blood pressure (mmHg) as a measure of safety and tolerability.
时间窗: Baseline through the treatment period and end of study at approximately week 16.
Diastolic blood pressure measured in millimeters of mercury (mmHg) using standard clinical procedures at each study visit to assess safety and tolerability of ENV-294.
Observed value, change from baseline, and percent change from baseline in respiratory rate (breaths per minute) as a measure of safety and tolerability.
时间窗: Baseline through the treatment period and end of study at approximately week 16
Respiratory rate measured in breaths per minute using standard clinical procedures at each study visit to assess safety and tolerability of ENV-294.
Observed value, change from baseline, and percent change from baseline in body temperature (°F) as a measure of safety and tolerability.
时间窗: Baseline through the treatment period and the end of the study at approximately week 16
Body temperature measured in degrees Fahrenheit using standard clinical procedures at each study visit to assess safety and tolerability of ENV-294.
Change from baseline in hematocrit
时间窗: Baseline through approximately 16 weeks (end of study)
Assessment of change from baseline in hematocrit value to evaluate the safety and tolerability of ENV-294.
Change from baseline in white blood cell count with differential
时间窗: Baseline through approximately 16 weeks (end of study)
Assessment of change from baseline in white blood cell (WBC) count with differential to evaluate the safety and tolerability of ENV-294.
次要结局
- Plasma Tmax (time to reach maximum plasma concentration) of ENV-294(At each scheduled pharmacokinetic (PK) collection time point during the 12-week treatment period)
- To assess the efficacy of ENV-294 in participants with asthma over a 12-week Treatment Period(From baseline through the end of the study at approximately 16 weeks.)
- Plasma Cmax (maximum observed plasma concentration) of ENV-294(At each scheduled PK collection time point during the 12-week treatment period)
- Plasma AUC (area under the concentration-time curve) of ENV-294(At each scheduled pharmacokinetic (PK) collection time point during the 12-week treatment period)
- To assess the efficacy of ENV-294 in participants with asthma over a 12-week Treatment Period(Treatment period through the end of the study at approximately 16 weeks)
- To assess the efficacy of ENV-294 in participants with asthma over a 12-week Treatment Period(From first treatment dose until the end of the study at approximately 16 weeks)