A Randomized, Double-Blind, Placebo-controlled, Parallel Arm, 52-week Study to Assess Efficacy, Safety, Tolerability, and Pharmacokinetics of Two Doses of EXPD-101 in Participants With COPD
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 600
- 试验地点
- 20
- 主要终点
- Changes in electrocardiogram (ECG) parameters
研究概览
简要总结
This is a Phase 2 study of the efficacy, safety, tolerability and pharmacokinetics of two doses of EXPD-101 in participants with COPD. Study participants will be randomized to receive either study drug or placebo administered once daily for 52 weeks.
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
- 40 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Provided written informed consent for the study
- •Body mass index (BMI) ≥ 18.5 kg/m2 and < 35 kg/m2 at screening (weight ≥ 50 kg for males and ≥ 45 kg for females)
- •Diagnosis of COPD for at least 1 year
- •COPD with physician-confirmed diagnosis of chronic bronchitis (persistent, productive cough and sputum for at least 3 months in the past year)
- •At least 2 moderate or > 1 severe exacerbation within 12 months prior to screening
- •Current or ex-tobacco smokers with history of ≥ 10 pack-years (1 pack year = 20 cigarettes smoked per day for 1 year);
- •Stable maintenance therapy with either dual or triple inhaled therapy for ≥ 3 months prior to enrollment per below:
- •Dual therapy: long-acting beta-2 agonist/muscarinic antagonist (LABA/LAMA) or inhaled corticosteroids (ICS)/LAMA, or ICS/LABA OR
- •Triple therapy: ICS/LAMA/LABA
- •Post-BD FEV1/FVC < 0.7 and post-BD FEV1(% predicted) ≥ 40% at Screening
- •COPD Assessment Test (CAT) score ≥ 10 at Screening
- •If participant is of childbearing potential, must commit to practicing highly effective methods of birth control and not donating eggs during the study and at least 14 days after the last dose.
- •Male participants commit to the following during the study and for at least 14 days after the last dose:
- •Practice true sexual abstinence (refrain from heterosexual intercourse)
- •Use a condom with any female partner of childbearing potential and ensure that the partner uses a highly effective contraceptive method (eg, IUD/IUS, combined hormonal contraception, progestogen-only contraception, or bilateral tubal occlusion).
- •Be vasectomized (≥ 3 months prior to screening)
- •Refrain from donating sperm during the Treatment Period and for at least 14 days after the last dose of the IP
排除标准
- •COPD exacerbation within the 4 weeks prior to randomization.
- •Clinically important pulmonary disease other than COPD (eg, asthma, active lung infection, clinically significant bronchiectasis, pulmonary fibrosis, cystic fibrosis, lung cancer, alpha-1 antitrypsin deficiency, tuberculosis).
- •Significant immunodeficiency and/or positive serological tests for hepatitis B, hepatitis C, or known human immunodeficiency virus (HIV) infection.
- •Pneumonia requiring antibiotics or antiviral medication within 28 days prior to Visit
- •History of clinically significant infection (excluding pneumonia), acute upper or lower respiratory infection, requiring antibiotics or antiviral medication within 14 days prior to Visit
- •Evidence of active liver disease (with or without ongoing treatment)
- •Participants with a QT interval, from the ECG conducted at Screening Visit 1, corrected with Fridericia's formula (QTcF) > 450 msec (or QTcF > 480 msec in participants with bundle branch block).
- •Current or history, within the past year of Visit 1, of substance and/or alcohol abuse.
- •History of cancer except:
- •Participants who have had basal cell carcinoma, localized squamous cell carcinoma of the skin or in situ carcinoma of the cervix are eligible to participate in the study provided that curative therapy was completed at least 12 months prior to Visit 1
- •Participants who have had other malignancies are eligible provided that curative therapy was completed at least 5 years prior to Visit 1
- •Any clinically significant abnormal findings in physical examination, vital signs, hematology, clinical chemistry, or urinalysis during Screening Period, which in the opinion of the investigator, may put the participant at risk because of his/her 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.
- •Known history of allergy or reaction to any component of the investigational product formulation
- •Current treatment with biologic drugs for COPD (eg, dupilumab, mepolizumab) or use of Therapeutics, biologics within 5 half-lives or 4 months, whichever is longer, from randomization
- •Current long-term treatment with oxygen therapy > 12 hours per day
- •Use of immunoglobulin or blood products in 30 days prior to Screening
- •Received a live attenuated vaccine within 30 days prior to Screening
- •Participants who are participating in the acute phase of a pulmonary rehabilitation program, i.e. who started rehabilitation < 4 weeks prior to screening (Note: participants in the maintenance phase of a rehabilitation program can be included).
- •History or active conditions associated with the onset of non-hereditary palmoplantar keratosis:
- •Have any tooth that can potentially cause pain or infection as noted in the oral exam unless they are corrected before the study
- •Has active periodontal disease and are either:
- •Currently treated by a dentist for this condition or
- •Expected to have periodontal disease-related procedures within the study period
- •Are scheduled to have tooth extraction that will occur during the study period
研究组 & 干预措施
EXPD-101/FXS7553 Dose 1
Participants will receive EXPD-101/FXS7553 Dose 1, orally, once daily, for 52 weeks.
干预措施: EXPD-101/FXS7553 Dose 1 (Drug)
EXPD-101/FXS7553 Dose 2
Participants will receive EXPD-101/FXS7553 Dose 2, orally, once daily, for 52 weeks.
干预措施: EXPD-101/FXS7553 Dose 2 (Drug)
Placebo
Participants will receive a EXPD-101/FXS7553-matching placebo, tablets orally, once daily, for 52 weeks.
干预措施: Placebo (Drug)
结局指标
主要结局
Changes in electrocardiogram (ECG) parameters
时间窗: Over 52 weeks
ECG (graphical tracing that records the electrical signals of your heartbeat) parameters will be summarized.
Annualized rate of moderate and severe COPD exacerbations
时间窗: Over 52 Weeks
Effect of EXPD-101/FXS7553 compared with placebo on rate of moderate and severe COPD exacerbations. Moderate COPD exacerbation is defined as acute exacerbations of COPD that require either systemic corticosteroids (intramuscular (IM), intravenous, or oral) and/or antibiotics. Severe COPD exacerbation is defined as acute exacerbation of COPD requiring hospitalization or emergency room / urgent care visit ≥ 24 hours.
The number of participants experiencing an adverse events (AEs)
时间窗: Over 52 weeks
The number of participants experiencing an AE (an AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship) will be presented.
Changes in vital sign parameters
时间窗: Over 52 weeks
Vital signs, including systolic and diastolic BP (mmHg), heart rate (beats per minute), body temperature (°C), and respiratory rate will be listed and summarized.
Number of Participants with Clinically Significant Changes in Physical Examination Findings
时间窗: Over 52 weeks
Physical examination will be performed at each study visit by a qualified investigator. The following body systems will be assessed: ears, nose, throat, skin, cardiovascular, respiratory, musculoskeletal, and neurological.
Number of participants with clinically significant abnormalities
时间窗: Over 52 weeks
Clinical laboratory assessments including hematology, serum chemistry, and urinalysis will be performed at each study visit.
Changes in Physical Exam Parameters - Body Weight
时间窗: Over 52 weeks
Body weight measured using a calibrated scale at each study visit
次要结局
- Time to first moderate or severe COPD exacerbation(Over 52 Weeks)
- Change From Baseline in Quality of Life Questionnaire - St. George's Respiratory Questionnaire (SGRQ)(Baseline, Week 52)
- Change From Baseline at Week 52 in Postbronchodilator Forced Expiratory Volume in 1 Second (FEV1) and forced vital capacity (FVC)(Baseline, Week 52)
- Change From Baseline at Week 52 in Quality of Life Questionnaire - Evaluating Respiratory Symptoms (E-RS): COPD(Baseline, Week 52)
- Annualized rate of severe COPD exacerbations(Over 52 Weeks)
- Plasma Concentration and metabolites of EXPD-101/FXS755(Pre-dose at baseline, and Weeks 2, 4, 12, 28, 52 and 56.)
- Change from Baseline in sputum neutrophil elastase (NE) activity(Over 52 Weeks)
- Annualized rate of COPD exacerbations requiring Emergency Department visit and/or hospitalization(Over 52 Weeks)