Cystic fibrosis MedDRA version: 20.0 Level: PT Classification code 10011762 Term: Cystic fibrosis System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Sponsors
Vertex Pharmaceuticals Incorporated
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 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
Exclusion criteria
Exclusion criteria: 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 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Parts D and E: • To evaluate the safety and tolerability of VX-445 in TC with TEZ and IVA in subjects with cystic fibrosis (CF) • To evaluate the efficacy of VX-445 in TC with TEZ and IVA in subjects with CF Part F (Optional): • To evaluate the safety and tolerability of VX-445 in TC with TEZ and VX-561 (deuterated IVA, also known as CTP-656) in subjects with CF • To evaluate the efficacy of VX-445 in TC with TEZ and VX-561 in subjects with CF;Secondary Objective: Parts D and E: • To evaluate the pharmacodynamic (PD) effect of VX-445 in TC with TEZ and IVA on CFTR function in subjects with CF • To evaluate the PK of VX-445 when administered in TC with TEZ and IVA in subjects with CF • To evaluate the PK of TEZ, IVA, and their respective metabolites (M1-TEZ and M1-IVA) when administered in TC with VX-445 in subjects with CF Part F (Optional): • To evaluate the PD effect of VX-445 in TC with TEZ and VX-561 on CFTR function in subjects with CF • To evaluate the PK of VX-445 when administered in TC with TEZ and VX-561 in subjects with CF • To evaluate the PK of TEZ and metabolite (M1-TEZ), and VX-561 when administered in TC with VX-445 in subjects with CF;Primary end point(s): Parts D, E and F: • Safety and tolerability assessments of AEs, clinical laboratory values, standard 12-lead ECGs, vital signs, and pulse oximetry, and spirometry • Absolute change in percent predicted forced expiratory volume in 1 second (ppFEV1) from baseline through Day 29;Timepoint(s) of evaluation of this end point: Monitored throughout the study | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Parts D and E: • Absolute change in sweat chloride concentrations from baseline through Day 29 • Relative change in ppFEV1 from baseline through Day 29 • Absolute change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) respiratory domain score from baseline at Day 29 • PK parameters of VX-445, TEZ, M1-TEZ, IVA, and M1-IVA Part F: • Absolute change in sweat chloride concentrations from baseline through Day 29 • Relative change in ppFEV1 from baseline through Day 29 • Absolute change in CFQ-R respiratory domain score from baseline at Day 29 • PK parameters of VX-445, TEZ, M1-TEZ, and VX-561;Timepoint(s) of evaluation of this end point: Parts D1 and D2: Days 1, 8, 15, 29, 36, ETT Part E: Days 1, 15, 29, 43, 57, ETT Part F: Days 1, 8, 15, 29, ETT | — |
Countries
Australia, Belgium, Netherlands, United States
Contacts
Public ContactClinical Trials and Medical Info
Vertex Pharmaceuticals Incorporated
Outcome results
None listed