Phase 3b, Randomized, Double-blind, Placebo-controlled, Parallel Group Study to Assess the Safety, Efficacy, and Tolerability of Tezacaftor/Ivacaftor (TEZ/IVA) in an Orkambi-experienced Population Who Are Homozygous for the F508del CFTR Mutation
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 98
- 试验地点
- 53
- 主要终点
- Incidence of Respiratory Adverse Events of Special Interest (RAESIs)
研究概览
简要总结
Study VX16-661-114 (Study 114) is a Phase 3b, randomized, double-blind, placebo-controlled, parallel-group, multicenter study in subjects aged 12 years and older with CF who are homozygous for the F508del mutation on the cystic fibrosis transmembrane conductance regulator gene (CFTR) gene and who discontinued treatment with Orkambi due to respiratory symptoms considered related to treatment. This study is designed to evaluate the safety and efficacy of Tezacaftor/Ivacaftor (TEZ/IVA).
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
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Willing and able to comply with scheduled visits, treatment plan, study restrictions, laboratory tests, contraceptive guidelines, and other study procedures.
- •Prior discontinuation of Orkambi, with at least 1 respiratory sign or symptom considered related to therapy.
- •Resolution or stabilization of qualifying event(s) >28 days prior to Screening.
- •Discontinuation of Orkambi therapy must have occurred within approximately 12 weeks from the first dose of Orkambi.
- •Homozygous for F508del mutation in the CFTR gene as documented in the subject's medical record. If genotype documentation is not available in the medical record, genotyping will be performed during screening.
- •FEV1 ≥25% and ≤90% of predicted normal for age, sex, and height.
- •Stable CF disease as judged by the investigator.
- •Other protocol defined inclusion criteria could apply.
排除标准
- •History of any comorbidity that, in the opinion of the investigator, might confound the results of the study or pose an additional risk in administering study drug to the subject.
- •Recent rapid or progressive deterioration in respiratory status.
- •Receiving continuous oxygen at >2L/min or on face-mask ventilation.
- •Any protocol-defined exclusionary laboratory values at Screening.
- •Child-Pugh Class B or C hepatic impairment.
- •An acute upper or lower respiratory infection, pulmonary exacerbation, or change in therapy for pulmonary disease within 28 days before Day
- •Documentation of colonization with organisms associated with a more rapid decline in pulmonary status.
- •History of lung transplantation since most recent initiation of Orkambi.
- •History of alcohol or drug abuse in the past year as deemed by the investigator.
- •Participation in an investigational drug study or use of a CFTR modulator within 28 days or 5 terminal half-lives of the investigational drug or modulator (whichever is longer).
- •Use of restricted medications or foods within the specified window before the first dose of study drug, or an anticipated need or use of restricted medication or foods after the first dose of study drug.
- •Pregnant or nursing females: Females of child-bearing potential must have a negative pregnancy test at Screening and Day
- •Other protocol defined exclusion criteria could apply.
研究组 & 干预措施
Placebo
Participants received placebo matched to TEZ/IVA fixed-dose combination tablet orally once daily in the morning followed by placebo matched to IVA tablet orally once daily in the evening for 56 days.
干预措施: Placebo (Drug)
TEZ/IVA
Participants received TEZ 100 milligram (mg)/IVA 150 mg fixed-dose combination tablet orally once daily in the morning and IVA 150 mg tablet orally once daily in the evening for 56 days.
干预措施: Tezacaftor/Ivacaftor (Drug)
TEZ/IVA
Participants received TEZ 100 milligram (mg)/IVA 150 mg fixed-dose combination tablet orally once daily in the morning and IVA 150 mg tablet orally once daily in the evening for 56 days.
干预措施: Ivacaftor (Drug)
结局指标
主要结局
Incidence of Respiratory Adverse Events of Special Interest (RAESIs)
时间窗: Day 1 up to Day 84
RAESIs included chest discomfort, dyspnea (shortness of breath), respiration abnormal (chest tightness), asthma, bronchial hyperreactivity, bronchospasm, and wheezing.
次要结局
- Relative Change From Baseline in ppFEV1 at Average of Day 28 and Day 56 Measurements(Baseline, Day 28 and Day 56)
- Tolerability as Assessed by Number of Participants Who Discontinued Treatment(Day 1 through Day 56)
- Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)(Day 1 up to Day 84)
- Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Average of Day 28 and Day 56 Measurements(Baseline, Day 28 and Day 56)
- Absolute Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score at Average of Day 28 and Day 56 Measurements(Baseline, Day 28 and Day 56)