A Phase 2, Randomized, Double Blind, Controlled Study to Evaluate the Safety of VX-152 Combination Therapy in Adults With Cystic Fibrosis
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 80
- 主要终点
- Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
研究概览
简要总结
This is a Phase 2, randomized, double blind, placebo and active-controlled, parallel group, multicenter study designed to evaluate the safety and tolerability of VX-152 in Triple Combination (TC) with tezacaftor (TEZ; VX-661) and ivacaftor (IVA; VX-770) in subjects with cystic fibrosis (CF) who are heterozygous for the F508del mutation and a minimal function (MF) CFTR mutation not likely to respond to TEZ and/or IVA therapy (F508del/MF), or who are homozygous for the F508del mutation of the CF transmembrane conductance regulator (CFTR) gene (F508del/F508del).
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
- Triple (Participant, Care Provider, Investigator)
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
- •Willing and able to comply with scheduled visits, treatment pan, study restrictions, laboratory tests, contraceptive guidelines, and other study procedures.
- •Body weight ≥35 kg.
- •Sweat chloride value ≥ 60 mmol/L from test results obtained during screening.
- •Subjects must have an eligible CFTR genotype:
- •Cohorts 1A, 1B, 1C: Heterozygous for F508del and a minimal function mutation known or predicted not to respond to TEZ and/or IVA.
- •Cohorts 2A, 2B: Homozygous for F508del.
- •Subjects must have an FEV1 ≥40% and ≤90% of predicted normal for age, sex, and height at the Screening Visit.
- •Stable CF disease as judged by the investigator.
- •Willing to remain on a stable CF medication regimen through the planned end of treatment or if applicable the Safety Follow-up Visit.
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.
- •History of cirrhosis with portal hypertension.
- •Risk factors for Torsade de Pointes.
- •History of hemolysis.
- •Glucose-6-phosphate dehydrogenase (G6PD) deficiency assessed at Screening.
- •Clinically significant abnormal laboratory values at screening.
- •An acute upper or lower respiratory infection, pulmonary exacerbation, or changes in therapy for pulmonary disease within 28 days before the first dose of study drug.
- •Lung infection with organisms associated with a more rapid decline in pulmonary status.
- •An acute illness not related to CF within 14 days before the first dose of study drug.
- •A standard digital ECG demonstrating QTc >450 msec at screening.
- •History of solid organ or hematological transplantation.
- •History or evidence of cataract or lens opacity determined to be clinically significant by the ophthalmologist or optometrist, based on the ophthalmologic examination during the Screening Period.
- •History of alcohol or drug abuse in the past year, including but not limited to, cannabis, cocaine, and opiates, as deemed by the investigator.
- •Ongoing or prior participation in an investigational drug study with certain exceptions.
- •Use of commercially available CFTR modulator within 14 days before screening (applies only to Cohorts 1A, 1B, and 1C).
- •Pregnant or nursing females: Females of childbearing potential must have a negative pregnancy test at screening and Day 1.
研究组 & 干预措施
Part 1: Placebo
干预措施: Placebo (Drug)
Part 1 Cohort 1A: TC
干预措施: VX-152 (Drug)
Part 1 Cohort 1A: TC
干预措施: TEZ/IVA (Drug)
Part 1 Cohort 1A: TC
干预措施: IVA (Drug)
Part 1 Cohort 1B: TC
干预措施: VX-152 (Drug)
Part 1 Cohort 1B: TC
干预措施: TEZ/IVA (Drug)
Part 1 Cohort 1B: TC
干预措施: IVA (Drug)
Part 1 Cohort 1C: TC
干预措施: VX-152 (Drug)
Part 1 Cohort 1C: TC
干预措施: TEZ/IVA (Drug)
Part 1 Cohort 1C: TC
干预措施: IVA (Drug)
Part 2 Cohort 2A: TEZ/IVA
干预措施: TEZ/IVA (Drug)
Part 2 Cohort 2A: TEZ/IVA
干预措施: IVA (Drug)
Part 2 Cohort 2A: TEZ/IVA
干预措施: Placebo (Drug)
Part 2 Cohort 2A: TC
干预措施: VX-152 (Drug)
Part 2 Cohort 2A: TC
干预措施: TEZ/IVA (Drug)
Part 2 Cohort 2A: TC
干预措施: IVA (Drug)
Part 2 Cohort 2B: TEZ/IVA
干预措施: TEZ/IVA (Drug)
Part 2 Cohort 2B: TEZ/IVA
干预措施: IVA (Drug)
Part 2 Cohort 2B: TEZ/IVA
干预措施: Placebo (Drug)
Part 2 Cohort 2B: TC
干预措施: VX-152 (Drug)
Part 2 Cohort 2B: TC
干预措施: TEZ/IVA (Drug)
Part 2 Cohort 2B: TC
干预措施: IVA (Drug)
结局指标
主要结局
Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
时间窗: Day 1 Through Safety Follow-up Visit (Up to Day 43 for Part 1 and Day 71 for Part 2)
Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Day 15 for Part 1 and Part 2 Cohort 2A
时间窗: From Baseline at Day 15
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Absolute Change in ppFEV1 Through Day 29 for Part 2 Cohort 2B
时间窗: From Baseline Through Day 29
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
次要结局
- Absolute Change in Sweat Chloride Concentrations at Day 15 for Part 1 and Part 2 Cohort 2A(From Baseline at Day 15)
- Absolute Change in Sweat Chloride Concentrations Through Day 29 for Part 2 Cohort 2B(From Baseline Through Day 29)
- Relative Change in ppFEV1 at Day 15 for Part 1 and Part 2 Cohort 2A(From Baseline at Day 15)
- Relative Change in ppFEV1 Through Day 29 for Part 2 Cohort 2B(From Baseline Through Day 29)
- Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score at Day 15 for Part 1 and Part 2 Cohort 2A(From Baseline at Day 15)
- Absolute Change From Baseline in CFQ-R Respiratory Domain Score at Day 29 for Part 2 Cohort 2B(From Baseline at Day 29)
- Pre-dose Plasma Concentration (Ctrough) of VX-152, TEZ, M1-TEZ, IVA, and M1-IVA(Pre-dose at Day 8, Day 15 and Day 29)