EUCTR2017-000797-11-BE进行中（未招募）1 期
A Phase 1/2 Study of VX-445 in Healthy Subjects and Subjects with Cystic Fibrosis
适应症
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 104
研究概览
简要总结
暂无简介。
研究设计
- 研究类型
- Interventional clinical trial of medicinal product
入排标准
- 性别
- All
入选标准
- •Parts D, E and F
- •1. Subject will sign and date an ICF.
- •2. Willing and able to comply with scheduled visits, treatment plan, study restrictions,
- •laboratory tests, contraceptive guidelines, and other study procedures.
- •3. Subjects will be aged 18 years or older on the date of informed consent.
- •4. Body weight =35 kg.
- •5. Subjects must be able to produce a valid (quantity-sufficient) sweat sample at screening, in addition to having a sweat chloride value =60 mmol/L documented at screening or in aprevious laboratory report. If the initial screening collection results in insufficient sweat volume, then the sweat chloride collection may be repeated once, after approval by the medical monitor. For the laboratory report requirement, it is acceptable to use a sweat chloride value that was obtained before previous treatment with IVA, LUM/IVA, or an investigational CFTR modulator, if applicable.
- •6. Subjects must have an eligible CFTR genotype as noted below. If the screening CFTR
- •genotype result is not received before randomization, a previous CFTR genotype laboratory report may be used to establish eligibility. Note: Subjects who have been randomized and whose screening genotype does not confirm study eligibility must be discontinued from the study (Section 9.9).
- •Parts D and F: Heterozygous for F508del with a second CFTR allele carrying a MF mutation that is not expected to respond to TEZ, IVA, and TEZ/IVA (Appendix A)
- •Part E: Homozygous for F508del
- •7. Subjects must have an FEV1 =40% and =90% of predicted normal for age, sex, and height (equations of the Global Lung Function Initiative [GLI])12 at the Screening Visit. Spirometry measurements must meet American Thoracic Society/European Respiratory Society criteria13 for acceptability and repeatability.
- •8. Stable CF disease as judged by the investigator.
- •9. Willing to remain on a stable CF treatment regimen through the planned end of treatment or, if applicable, the Safety Follow-up Visit.
- •Are the trial subjects under 18? no
- •Number of subjects for this age range:
- •F.1.2 Adults (18-64 years) yes
- •F.1.2.1 Number of subjects for this age range 104
- •F.1.3 Elderly (>=65 years) no
- •F.1.3.1 Number of subjects for this age range
排除标准
- •Parts D, E and F
- •1. 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.
- •2. History of clinically significant cirrhosis with or without portal hypertension.
- •3. Risk factors for Torsade de Pointes, including but not limited to, history of any of the
- •following: familial long QT syndrome, chronic hypokalemia, heart failure, left ventricular
- •hypertrophy, chronic bradycardia, myocardial infarction, cardiomyopathy, history of
- •arrhythmia (ventricular or atrial fibrillation), obesity, acute neurologic events (subarachnoid hemorrhage, intracranial hemorrhage, cerebrovascular accident, or intracranial trauma), or autonomic neuropathy.
- •4. History of hemolysis.
- •5. G6PD deficiency, defined as G6PD activity less than the LLN or 70% of the mean of the
- •LLN and the ULN, whichever is greater.
- •6. Any of the following abnormal laboratory values at screening:
- •Hemoglobin <10 g/dL
- •Total bilirubin =2 × ULN
- •Aspartate transaminase (AST), alanine transaminase (ALT), gamma-glutamyl transpeptidase (GGT), or alkaline phosphatase (ALP) =3 × ULN
- •Abnormal renal function defined as glomerular filtration rate =50 mL/min/1.73 m2
- •(calculated by the Modification of Diet in Renal Disease Study Equation)14, 15
- •7. An acute upper or lower respiratory infection, pulmonary exacerbation, or changes in
- •therapy (including antibiotics) for sino-pulmonary disease within 28 days before the first
- •dose of study drug.
- •8. Lung infection with organisms associated with a more rapid decline in pulmonary status (e.g., Burkholderia cenocepacia, Burkholderia dolosa, and Mycobacterium abscessus). For subjects who have had a history of a positive culture in the past, the investigator will apply the following criteria to establish whether the subject is free of infection with such organisms:
- •The subject has had 2 respiratory tract cultures negative for these organisms within the
- •past 12 months, with no subsequent positive cultures.
- •These 2 respiratory tract cultures were separated by at least 3 months, and 1 of them was obtained within the past 6 months.
- •9. An acute illness not related to CF (e.g., gastroenteritis) within 14 days before the first dose of study drug.
- •10. A standard digital ECG demonstrating QTc >450 msec at screening. If QTc exceeds
- •450 msec for the screening ECG, the ECG should be repeated 2 more times during the
- •Screening Period, and the subject will be excluded if the average of the 3 QTc values is
- •>450 msec. As stated in Section 11.7.5.1, study sites should use QTcF unless they receive
- •approval in advance from the medical monitor to use QTcB.
- •11. History of solid organ or hematological transplantation.
- •12. History of alcohol or drug abuse in the past year, including but not limited to, cannabis, cocaine, and opiates, as deemed by the investigator.
- •13. Ongoing or prior participation in a study of an investigational treatment other than a CFTR modulator within 28 days or 5 terminal half-lives (whichever is longer) before screening. The duration of the elapsed time may be longer if required by local regulations.
- •14. Use of prohibited medications as defined in Table 9-4, within the specified window before the first dose of study drug.
- •15. For female subjects: Pregnant or nursing females. Females of childbearing potential must have a negative pregnancy test at screening, Day -28 (Part E only), and Day 1.
- •For male subjects: Male subjects with a fe
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