A Phase 1/2 Dose Escalation Study Evaluating the Safety, and Tolerability and Efficacy of VX-522 in Subjects 18 Years of Age and Older With Cystic Fibrosis and a CFTR Genotype Not Responsive to CFTR Modulator Therapy
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 26
- 试验地点
- 46
- 主要终点
- Safety and Tolerability as Assessed by Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
研究概览
简要总结
The purpose of this study is to evaluate the safety, and tolerability and efficacy of VX-522 in participants 18 years of age and older with cystic fibrosis and a cystic fibrosis transmembrane conductance regulator (CFTR) genotype not responsive to CFTR modulator therapy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Body mass index is less than (<) 30.0 kilograms per meter square (kg/m^2)
- •A total body weight greater than (>) 50 kg
- •Stable CF disease
- •CFTR gene mutations on both alleles that are not responsive to CFTR modulator therapy
- •o Example mutations include but are not limited to, mutations that do not produce CFTR protein (i.e., Class I): nonsense mutations (e.g., G542X, W1282X) and canonical splice mutations (e.g., 621+1G->T)
- •Forced expiratory volume in 1 second (FEV1) value for SAD: greater than or equal to (≥)40 percent (%), MAD: ≥ 50% to less than or equal to (≤) 90%
排除标准
- •History of uncontrolled asthma within a year prior to screening
- •History of solid organ or hematological transplantation
- •Hepatic cirrhosis with portal hypertension, moderate hepatic impairment (Child Pugh Score 7 to 9), or severe hepatic impairment (Child Pugh Score 10 to 15)
- •Arterial oxygen saturation on room air less than (<) 94% at screening
- •Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
Single Ascending Dose (SAD)
Participants grouped into different cohorts will receive a single ascending dose of VX-522.
干预措施: VX-522 mRNA therapy (Drug)
Multiple Ascending Dose (MAD) Cohort 1: VX-522
Participants will receive multiple ascending doses of VX-522.
干预措施: VX-522 mRNA therapy (Drug)
MAD Cohort 1: VX-522+ IVA
Following run-in period with ivacaftor (IVA), participants will receive multiple ascending doses of VX-522 with IVA.
干预措施: VX-522 mRNA therapy (Drug)
MAD Cohort 1: VX-522+ IVA
Following run-in period with ivacaftor (IVA), participants will receive multiple ascending doses of VX-522 with IVA.
干预措施: IVA (Drug)
MAD Cohort 2: VX-522+ IVA
Following run-in period with ivacaftor (IVA), participants will receive multiple ascending doses of VX-522 with IVA.
干预措施: VX-522 mRNA therapy (Drug)
MAD Cohort 2: VX-522+ IVA
Following run-in period with ivacaftor (IVA), participants will receive multiple ascending doses of VX-522 with IVA.
干预措施: IVA (Drug)
结局指标
主要结局
Safety and Tolerability as Assessed by Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
时间窗: From Day 1 Through Week 8 [SAD and MAD]
次要结局
- MAD: Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)(From Baseline at Day 29)
- MAD: Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)(From Baseline at Day 29)
- MAD: Safety and Tolerability as Assessed by Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)(From Day 1 Through Safety Follow-up Visit [up to Week 28])