A Master Protocol to Test the Impact of Discontinuing Chronic Therapies in People With Cystic Fibrosis on Highly Effective CFTR Modulator Therapy - Hypertonic Saline
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 370
- 试验地点
- 159
- 主要终点
- Absolute Change in FEV1 % Predicted From Week 0 to Week 6
研究概览
简要总结
Despite the increasingly common use of cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapies in treating cystic fibrosis (CF), it is still largely unknown whether or not other chronic therapies can be safely stopped. This SIMPLIFY sub-study is being done to test whether or not it is safe to stop taking inhaled hypertonic saline in those people that are also taking elexacaftor/tezacaftor/ivacaftor (ETI).
ETI is a combination CFTR modulator therapy that was approved by the Food and Drug Administration for people with CF who have at least one F508del mutation. The three drugs that make up ETI work together to allow many more chloride ions to move into and out of the cells, improving the balance of salt and water in the lungs. These changes result in better clearance of mucus from the lungs and improvements in lung function.
Inhaled hypertonic saline (HS) also improves clearance of mucus from the lungs to support lung function and has been available to people with CF for many years. HS is considered to be relatively burdensome and it is not known whether HS can improve or maintain lung function above what is already gained through ETI use.
The goal of this SIMPLIFY sub-study is to get information about whether or not it is safe to stop hypertonic saline by testing if there is a change in lung function in participants with cystic fibrosis (CF) who are assigned to stop taking HS as compared to those who are assigned to keep taking HS while continuing to take ETI.
This is a sub study of master protocol SIMPLIFY-IP-19, NCT04378153.
The sub study investigating the impact of discontinuing and continuing dornase alfa is registered under NCTXXXXXXX (will add once available).
详细描述
This SIMPLIFY sub-study (Hypertonic Saline (HS) Trial) is designed to evaluate the effects of discontinuing HS in people with cystic fibrosis (CF) age 12 and older currently taking the highly effective modulator elexacaftor/tezacaftor/ivacaftor (ETI). This is an open label two-arm randomized non-inferiority trial consisting of a 2-week screening period, randomization to continue or discontinue hypertonic saline, followed by a 6-week study period. Participants at trial entry will be randomized 1:1 to either continue or discontinue their HS therapy.
Clinical outcomes (forced expiratory volume in 1 second [FEV1], antibiotic use, pulmonary exacerbations, and patient reported outcomes), safety (adverse events) and patient reported outcomes to evaluate respiratory symptoms and the participant's perception of how stopping HS would impact their daily life will be evaluated in all subjects. Additionally, a subset of participants at selected study sites will participate in Multiple Breath Washout (MBW) to evaluate changes in lung clearance index (LCI).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of CF.
- •Age ≥ 12 years at the Screening Visit.
- •Forced expiratory volume in 1 second (FEV1) ≥ 70 % predicted at the Screening Visit if < 18 years old, and ≥ 60 % predicted at Screening Visit if ≥ 18 years old.
- •Clinically stable with no significant changes in health status within the 7 days prior to and including the Screening Visit.
- •Current treatment with elexacaftor/tezacaftor/ivacaftor (ETI) for at least the 90 days prior to and including the Screening Visit and willing to continue daily use for the duration of the study.
- •Currently taking hypertonic saline (at least 3%) for at least the 90 days prior to and including the Screening Visit and willing to continue daily use for the 2-week screening period.
排除标准
- •Active smoking or vaping.
- •Use of an investigational drug within 28 days prior to and including the Screening Visit.
- •Changes to chronic therapy (e.g., ibuprofen, azithromycin, inhaled tobramycin, aztreonam lysine) within 28 days prior to and including the Screening Visit. This includes new airway clearance routines.
- •Acute use of antibiotics (oral, inhaled or IV) or acute use of systemic corticosteroids for respiratory tract symptoms within 7 days prior to and including the Screening Visit.
- •Chronic use of systemic corticosteroids at a dose equivalent to ≥ 10mg per day of prednisone within 28 days prior to and including the Screening Visit.
- •Antibiotic treatment for nontuberculous mycobacteria (NTM) within 28 days prior to and including the Screening Visit.
结局指标
主要结局
Absolute Change in FEV1 % Predicted From Week 0 to Week 6
时间窗: Week 0 to Week 6
Difference between study arms (discontinue - continue) in the absolute change in FEV1 % predicted from Week 0 to Week 6.
次要结局
- Absolute Change in LCI 2.5 From Baseline to Week 6(Baseline (Week 0 or Week -2) to Week 6)
- Absolute Change in Respiratory Symptoms, as Measured by the CF Respiratory Symptoms Diary-Chronic Respiratory Infection Symptom Severity Score (CRISS) From Week 0 to Week 6(Week 0 to Week 6)
- Absolute Change in Respiratory Symptoms, as Measured by CFQ-R Respiratory Domain From Week 0 to Week 6(Week 0 to Week 6)
- Absolute Change in FEV1 % Predicted From Week -2 to Week 0(Week -2 to Week 0)
- Absolute Change in FEV1 % Predicted From Week 0 to Week 2(Week 0 to Week 2)
- Number and Percent of Participants Initiating Acute Antibiotics From Week 0 to Week 6(Week 0 to Week 6)
- Number and Percent of Participants Hospitalized From Week 0 to Week 6(Week 0 to Week 6)
- Number and Percent of Participants Experiencing Pulmonary Exacerbations From Week 0 to Week 6(Week 0 to Week 6)
- Number and Percent of Participants Experiencing Adverse Events (AEs) From Week 0 to Week 6(Week 0 to Week 6)
- Rate of Adverse Events (AEs) From Week 0 to Week 6 Therapy Arms(Week 0 to Week 6)
- Number and Percent of Participants With Temporary or Permanent Changes From Assigned Therapy Regimen Due to Adverse Event From Week 0 to Week 6(Week 0 to Week 6)
研究者
Nicole Hamblett
Professor of Pediatrics, Division of Pulmonary and Sleep Medicine, University of Washington School of Medicine Adjunct Professor, Biostatistics, University of Washington School of Medicine Co-Executive Director, Cystic Fibrosis Therapeutics Development
Seattle Children's Hospital