A Phase 3 Efficacy and Safety Study of Ataluren (PTC124®) in Patients With Nonsense Mutation Cystic Fibrosis
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 279
- 试验地点
- 88
- 主要终点
- Absolute Change From Baseline in Percent-predicted Forced Expiratory Volume in One Second (ppFEV1) at Week 48
研究概览
简要总结
This is a Phase 3, international, multicenter, randomized, double-blind, placebo-controlled, efficacy and safety study of ataluren in patients with nonsense mutation cystic fibrosis (nmCF) not receiving chronic inhaled aminoglycosides.
详细描述
This study is to enroll 208 subjects (184 fully evaluable) with nonsense-mutation-mediated CF who are at least 6 years of age and have an forced expiratory volume in 1 second (FEV1) >= 40% and <= 90% of predicted. Subjects will be stratified based on age, inhaled antibiotic use, and baseline FEV1, and will be randomized in a 1:1 ratio to receive oral ataluren administered 3 times per day (TID) at respective morning, midday, and evening doses of 10-, 10-, and 20-mg/kg or placebo. Based on the results of a previously conducted study, patients treated with chronic inhaled aminoglycosides (including TOBI) will not be eligible for participation. Spirometry measurement at the screening visit will establish patient eligibility for inclusion based on lung function. FEV1 stability will be assessed during the approximately 4-week screening period, at the conclusion of which patients will be required to demonstrate a relative change in %-predicted FEV1 of less than 15% when compared to the screening value. Assessments will be performed every 8 weeks, depending upon the outcome measure.
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
- 6 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Evidence of signed and dated informed consent/assent document(s) indicating that the subject (and/or his parent/legal guardian) has been informed of all pertinent aspects of the trial
- •Age >=6 years.
- •Body weight >=16 kg.
- •Sweat chloride >60 milliequivalent per liter (mEq/L)
- •Documentation of the presence of a nonsense mutation in at least 1 allele of the cystic fibrosis transmembrane conductance regulator (CFTR) gene, as determined by genotyping performed at a laboratory certified by the College of American Pathologists (CAP), or under the Clinical Laboratory Improvement Act/Amendment (CLIA), or by an equivalent organization
- •Verification that a blood sample has been drawn for sequencing of the CFTR gene
- •Ability to perform a valid, reproducible spirometry test using the study-specific spirometer with demonstration of an FEV1 >=40% and <=90% of predicted
- •Demonstration at Visit 2 of a valid %-predicted FEV1 within 15% of the Screening % predicted FEV1 value
- •Resting oxygen saturation (as measured by pulse oximetry) >=92% on room air.
- •Confirmed screening laboratory values within pre-specified ranges
- •In subjects who are sexually active, willingness to abstain from sexual intercourse or employ a barrier or medical method of contraception during the study drug administration and 60-day follow-up period
- •Willingness and ability to comply with all study procedures and assessments, including scheduled visits, drug administration plan, study procedures, laboratory tests, and study restrictions
排除标准
- •Known hypersensitivity to any of the ingredients or excipients of the study drug
- •Previous participation in the Phase 3 trial of ataluren (PTC124-GD-009-CF).
- •Any change (initiation, change in type of drug, dose modification, schedule modification, interruption, discontinuation, or re-initiation) in a chronic treatment/prophylaxis regimen for Cystic Fibrosis (CF) or for CF-related conditions within 4 weeks prior to screening
- •Chronic use of inhaled aminoglycosides (eg, tobramycin) or use of inhaled aminoglycosides within 4 weeks prior to screening.
- •Exposure to another investigational drug within 4 weeks prior to screening
- •Ongoing participation in any other therapeutic clinical trial
- •Evidence of pulmonary exacerbation or acute upper or lower respiratory tract infection (including viral illnesses) within 3 weeks prior to screening
- •Treatment with intravenous antibiotics within 3 weeks prior to screening
- •Ongoing immunosuppressive therapy (other than corticosteroids)
- •Ongoing warfarin, phenytoin, or tolbutamide therapy
- •History of solid organ or hematological transplantation
- •Major complications of lung disease (including massive hemoptysis, pneumothorax, or pleural effusion) within 8 weeks prior to screening
- •Known portal hypertension
- •Positive hepatitis B surface antigen, hepatitis C antibody test, or human immunodeficiency virus (HIV) test
- •Pregnancy or breast-feeding
- •Current smoker or a smoking history of >=10 pack-years (number of cigarette packs/day x number of years smoked).
- •Prior or ongoing medical condition (eg, concomitant illness, alcoholism, drug abuse, psychiatric condition), medical history, physical findings, electrocardiogram (ECG) findings, or laboratory abnormality that, in the investigator's opinion, could adversely affect the safety of the subject, makes it unlikely that the course of treatment or follow-up would be completed, or could impair the assessment of study results
研究组 & 干预措施
Ataluren (PTC124®)
Participants received ataluren as oral powder for suspension at the dosages of 10, 10, and 20-mg/kg at morning, midday and evening, respectively for 48 weeks of treatment duration or until treatment discontinuation.
干预措施: Ataluren (PTC124®) (Drug)
Placebo
Participants received matching placebo orally at morning, midday and evening for 48 weeks of treatment duration or until treatment discontinuation.
干预措施: Placebo (Drug)
结局指标
主要结局
Absolute Change From Baseline in Percent-predicted Forced Expiratory Volume in One Second (ppFEV1) at Week 48
时间窗: From Baseline to Week 48
The FEV1 is the volume of air forcibly exhaled in one second and is measured using forced expiratory air spirometry. Change in ppFEV1 at Week 48 was defined as the average between the change from baseline at Week 40 and that at Week 48. Baseline for ppFEV1 was defined as an average of ppFEV1 at Screening (Weeks -4 to -1) and Baseline (Day 1) visits.
次要结局
- Change From Baseline in the Cystic Fibrosis Questionnaire - Revised (CFQ-R) Respiratory Domain at Week 48(Baseline (Day 1) and Week 48)
- 48-week Rate of Pulmonary Exacerbations(Week 48)
- Number of Participants With TEAEs by Severity and Relationship to Study Drugs(From study drug administration to 4-week post treatment follow-up visit (approximately 52 weeks))
- Change From Baseline in Body Mass Index (BMI) at Week 48(Baseline (Day 1) and Week 48)
- Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (SAEs)(From study drug administration to 4-week post treatment follow-up visit (approximately 52 weeks))
- Number of Participants With SAEs by Severity and Relationship to Study Drugs(From study drug administration to 4-week post treatment follow-up visit (approximately 52 weeks))
- Number of Participants With Abnormal Vital Signs Reported as TEAEs(From study drug administration to 4-week post treatment follow-up visit (approximately 52 weeks))
- Number of Participants With Abnormal Electrocardiogram Reported as TEAEs(From study drug administration to 4-week post treatment follow-up visit (approximately 52 weeks))
- Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs(From study drug administration to 4-week post treatment follow-up visit (approximately 52 weeks))