APPLAUD: A Double-Blind, Randomized, Placebo-Controlled, Phase II Study of the Efficacy and Safety of LAU-7b in the Treatment of Cystic Fibrosis in Adults
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 166
- 试验地点
- 40
- 主要终点
- Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1%)
研究概览
简要总结
An International Phase II, double-blind, randomized, placebo-controlled study to evaluate the safety and efficacy of LAU-7b administered once-daily for 6 months for the treatment of CF.
详细描述
An International Phase II, double-blind, randomized, placebo-controlled study to evaluate the safety and efficacy of LAU-7b administered once-daily for 6 months for the treatment of CF. All patients will remain on their CF standard-of-care treatments over the trial duration.
The goal for the treatment with LAU-7b in CF is to preserve lung function by reducing the persistent inflammation in the lung and to improve its capacity to defend against resistant bacteria such as Pseudomonas aeruginosa.
The treatment regimen will consist of 6 consecutive "dosing cycles" of 21 days each, spaced by study drug-free periods of 7 days. A total of 136 eligible adult patients with CF will be randomized to receive 300 mg LAU-7b or placebo in a 1:1 ratio. The participation in the study will last about 7 months.
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
Patients will be randomly assigned to take either the active drug (fenretinide capsule) or a matching inactive placebo (inactive capsule).
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Screening FEV1 between 40% and 100% predicted value for age, gender and height, in patients capable of properly performing the test;
- •History of pulmonary exacerbation, defined as at least one (1) pulmonary exacerbation in the year prior to Screening which resulted in documented intravenous or Oral antibiotics;
- •Patients are eligible independently of their history of pulmonary Pseudomonas aeruginosa (PsA) infection and their PsA status at screening;
- •If taking Kalydeco® (ivacaftor), Orkambi® (ivacaftor/lumacaftor), Symdeko® (ivacaftor/tezacaftor) or other commercially available CFTR modulator products, patients must be taking it for a minimum of 3 months prior to screening if naïve to CFTR modulators and 1 month if switched from another CFTR modulator product and deemed to tolerate it;
- •No change in CF and allowed systemic chronic therapy for a minimum of 5 weeks prior to randomization, of which 2 weeks minimum are prior to screening;
- •Female patients of child bearing potential should be on highly effective contraceptive methods during the study;
- •Male patients with spouse or partner of child bearing potential, or pregnant, are eligible if they use an appropriate method of contraception.
排除标准
- •Pregnancy: due to the potential teratogenic effects of retinoids, pregnant women are NOT eligible;
- •Breast milk feeding by study patient is NOT allowed;
- •Clinically abnormal renal function: serum creatinine > 132 μM (1.5 mg/dL);
- •Clinically abnormal liver function: Total bilirubin >1.5 x ULN (in the absence of demonstrated Gilbert's syndrome), alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) > 2.5 x ULN;
- •Patients with plasma retinol levels below 0.7 µM;
- •Presence of nyctalopia or hemeralopia at enrolment, or any other serious retinal, ophthalmological condition;
- •Presence of serious dermatological conditions at entry, including inflammatory or xerotic skin pathologies such as psoriasis or ichthyosis;
- •Intake of chronic systemic steroids in the month prior to screening and during the study;
- •History of acute infections (viral/bacterial/fungal) within 5 weeks prior to randomization, of which 2 weeks minimum are prior to screening, whether or not treated and resolved;
- •Presence of infection with Burkholderia cepacia (including all species within the Burkholderia cepacia complex group, and Burkholderia gladioli) in the 12 months prior to screening;
- •Patients with a confirmed diagnosis (as per the Cystic Fibrosis Foundation diagnostic criteria) of Allergic BronchoPulmonary Aspergillosis (ABPA) and actively being treated with corticosteroids and/or anti fungal agents.
研究组 & 干预措施
LAU-7b
Active drug fenretinide (as LAU-7b capsules)
干预措施: LAU-7b (Drug)
Placebo
Placebo oral capsule (as inactive capsules identical to active arm)
干预措施: Placebo oral capsule (Drug)
结局指标
主要结局
Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1%)
时间窗: From baseline to 24 weeks
Standardized, serial FEV1 measurements were performed during the trial by the clinical sites using standardized spirometers. All spirometry measurements were centrally read and validated by the spirometry provider, Vitalograph. The outcome measure is presented using the Least Squares Mean at the Week 24 time point and the Least Squares Mean of all post-baseline time points through Week 24 averaged.
Summary of Treatment Emergent Adverse Events With ≥ 10% Incidence
时间窗: From Baseline to 28 weeks
This was assessed through adverse event monitoring at all visits, including spontaneously reported events and those obtained through serial probing of the subjects, and from safety laboratory tests
次要结局
- The Proportion of Patients Achieving Normalization of the Arachidonic Acid, Docosahexaenoic Acid and Their Ratio in Phospholipids(From baseline to 28 weeks)
- The Absolute Change in FEV1 Percent Predicted at 3, 7, 11, 15, 24 and 28 Weeks Into the Trial(From baseline to 3, 7, 11, 15, 24 and 28 weeks into the trial)
- The Relative (%) Change in FEV1 Percent Predicted at 3, 7, 11, 15, 24 and 28 Weeks Into the Trial(From baseline to 3, 7, 11, 15, 24 and 28 weeks into the trial)
- The Time to First Protocol-Defined Pulmonary Exacerbation(From baseline to 28 weeks)
- The Number Per Subject of Protocol-Defined Pulmonary Exacerbations (PEx) During the Trial(From baseline to 28 weeks)
- The Time to First Change and Usage of Antibiotic (Other Than Chronic Inhaled Antibiotics Already Started Prior to Trial or Oral Chronic Azithromycin)(From baseline to 28 weeks)
- Usage (Number of Antibiotic Treatments) of Antibiotic (Other Than Chronic Inhaled Antibiotics Already Started Prior to Trial or Oral Chronic Azithromycin)(From baseline to 28 weeks)
- Usage (Days) of Antibiotic (Other Than Chronic Inhaled Antibiotics Already Started Prior to Trial or Oral Chronic Azithromycin)(From baseline to 28 weeks)
- The Change From Baseline of Systemic Markers of Inflammation in Blood(Change from baseline to Week 24)
- The Change From Screening of the Body Weight(From screening to 28 weeks)
- The Change From Screening of the Body Mass Index (BMI)(From screening to 28 weeks)
- The Overall Change From Screening of the Pseudomonas Aeruginosa Density (Colony Forming Units) in the Sputum(From screening to Week 24)
- The Impact (From Baseline) on Overall Health, Daily Life, Perceived Well-being and Symptoms Measured With the Cystic Fibrosis Questionnaire-Revised (CFQ-R)(From baseline to 24 weeks)
- The Change in Metabolipidomic Profile and in Markers of Oxidative Stress in Blood(From baseline to 24 weeks)