A Phase 3, Open Label Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of VX-661 in Combination With Ivacaftor in Subjects 6 Through 11 Years of Age With Cystic Fibrosis, Homozygous or Heterozygous for the F508del CFTR Mutation
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 83
- 主要终点
- Part A: Area Under the Concentration Versus Time Curve During Dosing Interval (AUCtau) of TEZ and IVA
研究概览
简要总结
This is a Phase 3, 2-part (Part A and Part B), open label, multicenter study evaluating the pharmacokinetic (PK), safety, and tolerability of multiple doses of tezacaftor (TEZ) in combination with ivacaftor (IVA) in subjects 6 through 11 years of age with CF who are homozygous or heterozygous for the F508del- CF transmembrane conductance regulator protein (CFTR) mutation.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 6 Years 至 11 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects who weigh ≥15 kg without shoes at the Screening Visit.
- •All genotypes as specified by the study protocol are eligible in Part A.
- •The following genotypes are eligible in Part B:
- •homozygous for the F508del CFTR mutation
- •heterozygous for the F508del CFTR mutation and with a second allele with a CFTR mutation predicted to have residual function.
- •heterozygous for the F508del CFTR mutation and with a second CFTR allele with a gating defect that is clinically demonstrated to be ivacaftor responsive
- •Subjects with a confirmed diagnosis of CF defined as a sweat chloride value ≥60 mmol/L or chronic sinopulmonary and/or gastrointestinal disease consistent with a diagnosis of CF. Subjects who are homozygous for the F508del-CFTR mutation must have a sweat chloride value ≥60 mmol/L.
- •Subjects with ppFEV1 of ≥40 percentage points at the Screening Visit
- •Subjects with stable CF disease as deemed by the investigator at the Screening Visit.
- •Subjects who are willing to remain on their stable CF medication regimen through Day 14 (Part A) or through Week 24 (Part B) or, if applicable, through the Safety Follow up Visit.
- •Subjects who are able to swallow tablets.
- •Female subjects of childbearing potential must have a negative serum pregnancy test at the Screening Visit and a negative urine pregnancy test at the Day 1 Visit before receiving the first dose of study drug.
- •Subjects of childbearing potential who are sexually active must meet the contraception requirements
排除标准
- •History of any comorbidity reviewed at the Screening Visit 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.
- •Any clinically significant laboratory abnormalities at the Screening Visit that would interfere with the study assessments or pose an undue risk for the subject.
- •An acute upper or lower respiratory infection, pulmonary exacerbation, or changes in therapy for pulmonary disease within 28 days before Day 1
- •Colonization with organisms associated with a more rapid decline in pulmonary status.
- •A standard 12 lead ECG demonstrating QTc >450 msec at the Screening Visit.
- •History of solid organ or hematological transplantation at the Screening Visit.
- •Ongoing or prior participation in an investigational drug study or use of commercially available CFTR modulator (except physician-prescribed Kalydeco for approved indications) within 30 days of screening.
- •Use of restricted medication or food within a specified duration before the Screening Visit or first dose of study drug and/or unwillingness to maintain the restrictions.
- •History or evidence of cataract, lens opacity, Y-suture, or lamellar rings determined to be clinically significant by the ophthalmologist during the ophthalmologic examination at the Screening Visit.
- •Pregnant and nursing females.
研究组 & 干预措施
Part A
Participants weighing <25 kg received TEZ 50 mg once daily/IVA 75 mg q12h orally for 14 days.
Participants weighing ≥25 kg received TEZ 50 mg once daily/IVA 150 mg q12h orally for 14 days.
干预措施: IVA (Drug)
Part A
Participants weighing <25 kg received TEZ 50 mg once daily/IVA 75 mg q12h orally for 14 days.
Participants weighing ≥25 kg received TEZ 50 mg once daily/IVA 150 mg q12h orally for 14 days.
干预措施: TEZ (Drug)
Part B
Participants weighing <40 kg received TEZ 50 mg/IVA 75 mg as fixed dose combination orally once daily in the morning and IVA 75 mg orally once daily in the evening for 24 weeks.
Participants weighing ≥40 kg received TEZ 100 mg/IVA 150 mg as fixed dose combination orally once daily in the morning and IVA 150 mg orally once daily in the evening for 24 weeks.
干预措施: TEZ/IVA (Drug)
Part B
Participants weighing <40 kg received TEZ 50 mg/IVA 75 mg as fixed dose combination orally once daily in the morning and IVA 75 mg orally once daily in the evening for 24 weeks.
Participants weighing ≥40 kg received TEZ 100 mg/IVA 150 mg as fixed dose combination orally once daily in the morning and IVA 150 mg orally once daily in the evening for 24 weeks.
干预措施: IVA (Drug)
结局指标
主要结局
Part A: Area Under the Concentration Versus Time Curve During Dosing Interval (AUCtau) of TEZ and IVA
时间窗: Day 1 and Day 14
Part A: Maximum Observed Concentration (Cmax) of TEZ and IVA
时间窗: Day 1 and Day 14
Part B: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
时间窗: Day 1 up to Week 28
次要结局
- Part A: Cmax of TEZ Metabolites (M1-TEZ, M2-TEZ) and IVA Metabolites (M1-IVA, M6-IVA)(Day 1 and Day 14)
- Part A: AUCtau of TEZ Metabolites (M1-TEZ, M2-TEZ) and IVA Metabolites (M1-IVA, M6-IVA)(Day 1 and Day 14)
- Part B: Absolute Change in Sweat Chloride(From Baseline through Week 24)
- Part B: Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score(From Baseline through Week 24)
- Part B: Cmax of TEZ, TEZ Metabolites (M1-TEZ, M2-TEZ), IVA, and IVA Metabolites (M1-IVA, M6-IVA)(Week 16)
- Part A: Number of Participants With AEs and SAEs(Day 1 up to Day 28)
- Part B: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)(From Baseline through Week 24)
- Part B: Relative Change in ppFEV1(From Baseline through Week 24)
- Part B: Absolute Change in Weight-for-age Z-Score(From Baseline at Week 24)
- Part B: Absolute Change in Height(From Baseline at Week 24)
- Part B: Absolute Change in Height-for-age z-Score(From Baseline at Week 24)
- Part B: AUCtau of TEZ, TEZ Metabolites (M1-TEZ, M2-TEZ), IVA, and IVA Metabolites (M1-IVA, M6-IVA )(Week 16)
- Part B: Absolute Change in Weight(From Baseline at Week 24)
- Part B: Absolute Change in Body Mass Index (BMI)(From Baseline at Week 24)
- Part B: Absolute Change in BMI-for-age z-Score(From Baseline at Week 24)